Keywords: Transmission distortion
Signatures of sex ratio distortion in humans
35441James Guy Baldwin-Brown, Sergiusz Wesolowski, Raquel Mae Reisinger, et al., bioRxiv, 2026-02-10 18:42:47.
Segregation distortion, the disproportionate inheritance of selfish genetic elements, is an important evolutionary force. While many species carry distorters, it is not clear if humans do. Major limitations for detecting human distortion are the small size of human families and the lack of genetic markers in most subjects. Here, we present evidence of strong distortion in a large human pedigree. We analyzed pedigrees from the Utah Population Database and identified lineages with a high chance of carrying a distorter. In particular, we identified a family that preferentially produced male offspring at a 2:1 ratio. This pattern is consistent with a distorting Y-chromosome, a rarity in species with degenerate Y-chromosomes. The detection of such non-Mendelian inheritance patterns suggests that human genomes may harbor segregation distorters.
A systematic review and critical analysis of the evidence for transmission ratio distortion in humans
35379Ziyi Dai, Gregory Costain, Genetics, 2026-01-14 16:36:37.
Mendel's law of equal segregation states that during gamete formation, the 2 alleles at a gene locus segregate such that each gamete has an equal probability of containing either allele. Transmission ratio distortion (TRD) occurs when 1 of the 2 alleles from either parent is preferentially transmitted to the offspring, resulting in a deviation from the expected 1:1 ratio. Although TRD has been observed and studied in nonhuman species, the full extent and underlying biology of TRD in humans remains poorly summarized. Here we present a systematic review to assess evidence of TRD in the human genome, tracing reports from the 1970s through 2025. Overall, 96 studies including 42 different human variants/genes/loci met inclusion criteria. These studies provided only preliminary and/or conflicting evidence of TRD. Study methods were limited by multiple recurrent biases. Experimental validation of the biological mechanism(s) underlying the putative distortion was rarely performed or possible. TRD warrants renewed attention in the field of human genetics, especially with the growing availability of very large, family-based genome-wide sequencing datasets.
Influence of genetic factors of humans, mosquitoes and parasites, on the evolution of Plasmodium falciparum infections, malaria transmission and genetic control methods: a review of the literature
34903Nikiema, S., Soulama, I., Ampofo, G.D. et al., BMC Medical Genomics, 18. 2025-06-06 08:52:12.
Despite significant progress, malaria remains a public health problem in many regions, particularly in sub-Saharan Africa. This situation is partly explained by the mosquito’s resistance to insecticides and the emergence of parasite resistance to antimalarial drugs. Indeed, in spite of the various vectors’ controls, insecticide resistance emerges from multi-generational selection and poses worldwide concern. In parallel, artemisinin resistance unfortunately emerged independently in multiple countries in eastern Africa. Since 2014, artemisinin resistance has been observed in 6 countries in Africa and, more concerningly, the evidence from longitudinal molecular surveys in these countries suggests that it is spreading. While phenotypic evidence of treatment failure is still limited, the increasing reports of validated artemisinin resistance mutations are alarming. Unlike the emergence of artemisinin resistance in South-East Asia, our understanding of the genetic determinants of artemisinin resistance and our ability to sequence and map the spread of resistance are significantly greater. In addition to mosquito and parasite genetics affecting malaria evolution, many human individual variants have been identified that are associated with malaria protection, but the most important of all relates to the structure or function of red blood cells, the classical polymorphisms that causes sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. In that biological complex context, there is a need to characterize the various genetic factors in Plasmodium falciparum, humans and mosquitoes that are potentially associated with resistance to antimalarial drugs and insecticides, and their involvement in the evolution, severity and transmission of malaria. In this direction, A comprehensive literature review was conducted to capture the objectives highlighted above. The advances in genomic surveillance and emerging genetic control strategies, such as gene drive technology were also considered in this review. We used search engines such as PubMed and Google scholar to retrieve articles useful to the objective of this paper and information on the knowledge of genetic factors and methods that contributed to malaria control were synthesized.
An eco-epidemiological model for malaria with Microsporidia MB as bio-control agent
34793Mfangnia CNT, Tonnang HEZ, Tsanou B, Keith Herren J, Modeling Earth Systems and Environment, 11. 2025-04-23 10:24:11.
Microsporidia MB is an endosymbiont which naturally infects Anopheles mosquitoes. Due to its ability to block Plasmodium transmission, it shows potential as a bio-based agent for the control of malaria. Its self-sustainability is promising, as it can spread through both vertical and horizontal transmissions. However, its low prevalence in mosquito populations remains a challenge. We develop an eco-epidemiological mathematical model describing the co-dynamics of Microsporidia MB (within mosquito population) and malaria (within human population). The model is used to assess the potential of Microsporidia MB-infected mosquitoes on the control of malaria infection. The results on the basic reproduction numbers, the stability of the equilibria, and the existence of bifurcations are obtained, providing conditions for the extinction and persistence of MB-infected mosquitoes. We highlight relevant threshold parameters for the elimination and persistence of MB-infected mosquitoes and malaria-infected individuals. Using real data from Kenya, we found that, given a horizontal transmission rate between 0 and 0.5, a minimum vertical rate of 0.55 is required to avoid extinction of MB-infected mosquitoes. The predicted prevalence of MB-infected mosquitoes using transmission rates reported from lab experiments align with the observed low prevalence of MB-infected mosquitoes in the field, thereby validating our model and results. Finally, predictions indicate that increasing MB mosquito infection could effectively control malaria, with target prevalence varying by region: 15% in Highland, 40% on the coast, and 70% in the Lake region. This study offers insights into the use of bio-based vector population replacement solutions to reduce malaria incidence in regions where Microsporidia MB is prevalent.
Wolbachia Invasion in Mosquitoes with Incomplete CI, Imperfect Maternal Transmission and Maturation Delay
32710Ma X, Su Y, Bulletin of Mathematical Biology, 2024-10-22 17:32:46.
The mechanism of cytoplasmic incompatibility (CI) is important in the study of Wolbachia invasion in wild mosquitoes. Su et al. (Bull Math Biol 84(9):95, 2022) proposed a delay differential equation model by relating the CI effect to maturation delay. In this paper, we investigate the dynamics of this model by allowing the same density-dependent death rate and distinct density-independent death rates. Through analyzing the existence and stability of equilibria, we obtain the parameter conditions for Wolbachia successful invasion if the maternal transmission is perfect. While if the maternal transmission is imperfect, we give the ranges of parameters to ensure failure invasion, successful invasion and partially suppressing, respectively. Meanwhile, numerical simulations indicate that the system may exhibit monostable and bistable dynamics when parameters vary. Particularly, in the bistable situation an unstable separatrix, like a line, exists when choosing constant functions as initial values; and the maturation delay affects this separatrix in an interesting way.
Autosomal suppression of sex-ratio meiotic drive influences the dynamics of X and Y chromosome coevolution
31322Anjali Gupta, Robert L Unckless, Journal of Heredity, 2024-09-03 15:54:00.
Sex-ratio meiotic drivers are selfish genes or gene complexes that bias the transmission of sex chromosomes resulting in skewed sex ratios. Existing theoretical models have suggested the maintenance of a four-chromosome equilibrium (with driving and standard X and suppressing and susceptible Y) in a cyclic dynamic, studies of natural populations have failed to capture this pattern. Although there are several plausible explanations for this lack of cycling, interference from autosomal suppressors has not been studied using a theoretical population genetic framework even though autosomal suppressors and Y-linked suppressors coexist in natural populations of some species. In this study, we use a simulation-based approach to investigate the influence of autosomal suppressors on the cycling of sex chromosomes. Our findings demonstrate that the presence of an autosomal suppressor can hinder the invasion of a Y-linked suppressor under some parameter space, thereby impeding the cyclic dynamics, or even the invasion of Y-linked suppression. Even when a Y-linked suppressor invades, the presence of an autosomal suppressor can prevent cycling. Our study demonstrates the potential role of autosomal suppressors in preventing sex chromosome cycling and provides insights into the conditions and consequences of maintaining both Y-linked and autosomal suppressors.
Functional and evolutionary constraints of wtf killer meiotic drivers
31213Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders, bioRxiv, 2024-08-29 10:38:59.
Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver- heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver- gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.
Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems
31181Sally Adams; Andre Pires-daSilva, Biochemical Society Transactions, 2024-08-25 20:35:26.
The non-Mendelian transmission of sex chromosomes during gametogenesis carries significant implications, influencing sex ratios and shaping evolutionary dynamics. Here we focus on known mechanisms that drive non-Mendelian inheritance of X chromosomes during spermatogenesis and their impact on population dynamics in species with different breeding systems. In Drosophila and mice, X-linked drivers targeting Y-bearing sperm for elimination or limiting their fitness, tend to confer unfavourable effects, prompting the evolution of suppressors to mitigate their impact. This leads to a complex ongoing evolutionary arms race to maintain an equal balance of males and females. However, in certain insects and nematodes with XX/X0 sex determination, the preferential production of X-bearing sperm through atypical meiosis yields wild-type populations with highly skewed sex ratios, suggesting non-Mendelian transmission of the X may offer selective advantages in these species. Indeed, models suggest X-meiotic drivers could bolster population size and persistence under certain conditions, challenging the conventional view of their detrimental effects. Furthering our understanding of the diverse mechanisms and evolutionary consequences of non-Mendelian transmission of X chromosomes will provide insights into genetic inheritance, sex determination, and population dynamics, with implications for fundamental research and practical applications.
Could X Centromeric Drive Underpin PCOS, Miscarriage and Other Age-Related Reproductive Issues?
31176Rhianna-lily Smith, Technology Networks, 2024-08-25 20:13:11.
One of the most prevalent conditions is polycystic ovary syndrome (PCOS), affecting 8-13% of women of reproductive age. Characterized by irregular menstrual cycles, excess androgen levels and ovarian cysts, PCOS is one of the leading causes of infertility. Despite its commonality, the underlying causes of the condition remain poorly understood. Dr. Tom Moore, a principal investigator in the School of Biochemistry and Cell Biology at University College Cork, has proposed a new hypothesis that may explain why human female reproduction is prone to multiple disorders. The X chromosome’s involvement in meiotic drive mechanisms could be a key factor in understanding why certain reproductive disorders are so common and persistent. Meiotic drive refers to a genetic phenomenon where certain genes manipulate the process of meiosis to increase their transmission to the next generation, often at the expense of other genes. In normal meiosis, genes have a 50% chance of being passed on to offspring, but meiotic drive skews this process, allowing "selfish" genes to be inherited more frequently than would be expected by chance. Due to genetic hitchhiking, this can introduce traits that may have detrimental effects on individual fitness. Antagonistic selection is an evolutionary concept where a genetic trait, which is beneficial in one context but harmful in another, may be passed on to a future generation. This typically occurs when a gene has different effects at different stages of life or under different environmental conditions. In the context of human evolution, antagonistic selection can help explain why certain reproductive disorders, like PCOS, might persist.
Escalation of genome defense capacity enables control of an expanding meiotic driver
30862Peiwei Chen, Katherine C. Pan, Eunice H. Park, Yicheng Luo, Yuh Chwen G. Lee, Alexei A. Aravin, bioRxiv, 2024-07-02 12:14:34.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate—a recently evolved and expanded selfish meiotic driver6–8—we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9–12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.
Transformation of meiotic drive into hybrid sterility in Drosophila
30352Jackson Bladen, Hyuck-Jin Nam, Nitin Phadnis, bioRxiv, 2024-05-21 19:05:25.
Hybrid male sterility is one of the fastest evolving intrinsic reproductive barriers between recently isolated populations. A leading explanation for the evolution of hybrid male sterility involves genomic conflicts with meiotic drivers in the male germline. There are, however, few examples directly linking meiotic drive to hybrid sterility. Here, we report that the Sex-Ratio chromosome of Drosophila pseudoobscura, which causes X-chromosome drive within the USA subspecies, causes near complete male sterility when moved into the genetic background of the Bogota subspecies. In addition, we show that this new form of sterility is genetically distinct from the sterility of F1 hybrid males in crosses between USA males and Bogota females. Our observations provide a tractable study system where non-cryptic drive within species is transformed into strong hybrid sterility between very young subspecies.
Meiotic drive against chromosome fusions in butterfly hybrids
28892Jesper Boman, Christer Wiklund, Roger Vila, Niclas Backström, bioRxiv, 2024-02-13 21:18:38.
Species frequently differ in karyotype, but heterokaryotypic individuals may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can thus serve as a mechanism for speciation between incipient lineages but their evolution poses a paradox. How does underdominant rearrangements evolve? One solution is the fixation of underdominant chromosomal rearrangements through genetic drift. However, this requires small and isolated populations. Fixation is more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate transmission ratio distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover a transmission bias favoring the fused state at chromosome with unknown polarization in one experiment and a transmission bias favoring the unfused state of derived fusions in both experiments. The latter result support a scenario where chromosome fusions can fix in populations despite counteracting effects of meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that this transmission bias can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why derived fusions may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.
Meiotic drive, postzygotic isolation, and the Snowball Effect
28418Robert L. Unckless, bioRxiv, 2023-11-14 12:43:39.
As populations diverge, they accumulate incompatibilities which reduce gene flow and facilitate the formation of new species. Simple models suggest that the genes that cause Dobzhansky-Muller incompatibilities should accumulate at least as fast as the square of the number of substitutions between taxa, the so-called snowball effect. We show, however, that in the special but possibly common case in which hybrid sterility is due primarily to cryptic meiotic (gametic) drive, the number of genes that cause postzygotic isolation may increase nearly linearly with the number of substitutions between species.
The suppression of a selfish genetic element increases a male’s mating success in a fly
28422Sophie Lyth, Andrea J. Betancourt, Tom A. R. Price, Rudi L. Verspoor, Ecology and Evolution, 2023-11-12 13:33:47.
X chromosome meiotic drive (XCMD) kills Y-bearing sperm during spermatogenesis, leading to the biased transmission of the selfish X chromosome. Despite this strong transmission, some natural XCMD systems remain at low and stable frequencies, rather than rapidly spreading through populations. The reason may be that male carriers can have reduced fitness, as they lose half of their sperm, only produce daughters, and may carry deleterious alleles associated with XCMD. Thus, females may benefit from avoiding mating with male carriers, yielding a further reduction in fitness. Genetic suppressors of XCMD, which block the killing of Y sperm and restore fair Mendelian inheritance, are also common and could prevent the spread of XCMD. However, whether suppressed males are as fit as a wild-type male remains an open question, as the effect that genetic suppressors may have on a male's mating success is rarely considered. Here, we investigate the mating ability of XCMD males and suppressed XCMD males in comparison to wild-type males in the fruit fly Drosophila subobscura, where drive remains at a stable frequency of 20% in wild populations where it occurs. We use both competitive and non-competitive mating trials to evaluate male mating success in this system. We found no evidence that unsuppressed XCMD males were discriminated against. Remarkably, however, their suppressed XCMD counterparts had a higher male mating success compared to wild-type controls. Unsuppressed XCMD males suffered 12% lower offspring production in comparison to wild-type males. This cost appears too weak to counter the transmission advantage of XCMD, and thus the factors preventing the spread of XCMD remain unclear.
Genetic conflict and the origin of multigene families: implications for sex chromosome evolution
28322E. Martí and A. M. Larracuente, Proceedings of the Royal Society B: Biological Sciences, 290:20231823. 2023-11-01 10:52:27.
Sex chromosomes are havens for intragenomic conflicts. The absence of recombination between sex chromosomes creates the opportunity for the evolution of segregation distorters: selfish genetic elements that hijack different aspects of an individual's reproduction to increase their own transmission. Biased (non-Mendelian) segregation, however, often occurs at a detriment to their host's fitness, and therefore can trigger evolutionary arms races that can have major consequences for genome structure and regulation, gametogenesis, reproductive strategies and even speciation. Here, we review an emerging feature from comparative genomic and sex chromosome evolution studies suggesting that meiotic drive is pervasive: the recurrent evolution of paralogous sex-linked gene families. Sex chromosomes of several species independently acquire and co-amplify rapidly evolving gene families with spermatogenesis-related functions, consistent with a history of intragenomic conflict over transmission. We discuss Y chromosome features that might contribute to the tempo and mode of evolution of X/Y co-amplified gene families, as well as their implications for the evolution of complexity in the genome. Finally, we propose a framework that explores the conditions that might allow for recurrent bouts of fixation of drivers and suppressors, in a dosage-sensitive fashion, and therefore the co-amplification of multigene families on sex chromosomes.
Testing a candidate meiotic drive locus identified by pool sequencing
27983D. A. Barbash, B. Jin, K. H. C. Wei and A.-M. Dion-Côté, G3 Genes|Genomes|Genetics, 2023-09-28 07:56:24.
Meiotic drive biases the transmission of alleles in heterozygous individuals, such that Mendel’s law of equal segregation is violated. Most examples of meiotic drive have been discovered over the past century based on causing sex-ratio distortion or the biased transmission of easily scoreable genetic markers that were linked to drive alleles. More recently, several approaches have been developed that attempt to identify distortions of Mendelian segregation genome-wide. Here we test a candidate female meiotic drive locus in Drosophila melanogaster, identified previously as causing a ∼54:46 distortion ratio using sequencing of large pools of backcross progeny. We inserted fluorescent visible markers near the candidate locus and scored transmission in thousands of individual progeny. We observed a small but significant deviation from the Mendelian expectation, however it was in the opposite direction to that predicted based on the original experiments. We discuss several possible causes of the discrepancy between the two approaches, noting that subtle viability effects are particularly challenging to disentangle from potential small-effect meiotic drive loci. We conclude that pool sequencing approaches remain a powerful method to identify candidate meiotic drive loci, but that genotyping of individual progeny at early developmental stages may be required for robust confirmation.
New perspectives on the causes and consequences of male meiotic drive
27827Courret, Cécile Wei, Xiaolu Larracuente, Amanda M., Current Opinion in Genetics & Development, 2023-09-11 08:34:27.
Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.
Meiotic segregation and post-meiotic drive of the Festuca pratensis B chromosome
27749R. Ebrahimzadegan, J. Fuchs, J. Chen, V. Schubert, A. Meister, A. Houben and G. Mirzaghaderi, Chromosome Research, 31:26. 2023-09-02 07:34:43.
In many species, the transmission of B chromosomes (Bs) does not follow the Mendelian laws of equal segregation and independent assortment. This deviation results in transmission rates of Bs higher than 0.5, a process known as “chromosome drive”. Here, we studied the behavior of the 103 Mbp-large B chromosome of Festuca pratensis during all meiotic and mitotic stages of microsporogenesis. Mostly, the B chromosome of F. pratensis segregates during meiosis like standard A chromosomes (As). In some cases, the B passes through meiosis in a non-Mendelian segregation leading to their accumulation already in meiosis. However, a true drive of the B happens during the first pollen mitosis, by which the B preferentially migrates to the generative nucleus. During second pollen mitosis, B divides equally between the two sperms. Despite some differences in the frequency of drive between individuals with different numbers of Bs, at least 82% of drive was observed. Flow cytometry-based quantification of B-containing sperm nuclei agrees with the FISH data.
Female meiotic drive in plants: mechanisms and dynamics
27709F. Finseth, Current Opinion in Genetics and Development, 82:102101. 2023-08-24 09:45:29.
Female meiosis is fundamentally asymmetric, creating an arena for genetic elements to compete for inclusion in the egg to maximize their transmission. Centromeres, as mediators of chromosomal segregation, are prime candidates to evolve via ‘female meiotic drive’. According to the centromere-drive model, the asymmetry of female meiosis ignites a coevolutionary arms race between selfish centromeres and kinetochore proteins, the by-product of which is accelerated sequence divergence. Here, I describe and compare plant models that have been instrumental in uncovering the mechanistic basis of female meiotic drive (maize) and the dynamics of active selfish centromeres in nature (monkeyflowers). Then, I speculate on the mechanistic basis of drive in monkeyflowers, discuss how centromere strength influences chromosomal segregation in plants, and describe new insights into the evolution of plant centromeres.
Female meiotic drive shapes the distribution of rare inversion polymorphisms in Drosophila melanogaster
27674S. A. Koury, Genetics, 2023-08-24 07:04:55.
In all species, new chromosomal inversions are constantly being formed by spontaneous rearrangement and then stochastically eliminated from natural populations. In Drosophila, when new chromosomal inversions overlap with a pre-existing inversion in the population, their rate of elimination becomes a function of the relative size, position, and linkage phase of the gene rearrangements. These altered dynamics result from complex meiotic behavior wherein overlapping inversions generate asymmetric dyads that cause both meiotic drive/drag and segmental aneuploidy. In this context, patterns in rare inversion polymorphisms of a natural population can be modeled from the fundamental genetic processes of forming asymmetric dyads via crossing-over in meiosis I and preferential segregation from asymmetric dyads in meiosis II. Here, a mathematical model of crossover-dependent female meiotic drive is developed and parameterized with published experimental data from Drosophila melanogaster laboratory constructs. This mechanism is demonstrated to favor smaller, distal inversions and accelerate the elimination of larger, proximal inversions. Simulated sampling experiments indicate that the paracentric inversions directly observed in natural population surveys of Drosophila melanogaster are a biased subset that both maximizes meiotic drive and minimizes the frequency of lethal zygotes caused by this cytogenetic mechanism. Incorporating this form of selection into a population genetic model accurately predicts the shift in relative size, position, and linkage phase for rare inversions found in this species. The model and analysis presented here suggest that this weak form of female meiotic drive is an important process influencing the genomic distribution of rare inversion polymorphisms.
Proliferation and dissemination of killer meiotic drive loci
27711E. C. Lai and A. A. Vogan, Current Opinion in Genetics and Development, 82:102100. 2023-08-23 09:49:07.
Killer meiotic drive elements are selfish genetic entities that manipulate the sexual cycle to promote their own inheritance via destructive means. Two broad classes are sperm killers, typical of animals and plants, and spore killers, which are present in ascomycete fungi. Killer meiotic drive systems operate via toxins that destroy or disable meiotic products bearing the alternative allele. To avoid suicidal autotargeting, cells that bear these selfish elements must either lack the toxin target, or express an antidote. Historically, these systems were presumed to require large nonrecombining haplotypes to link multiple functional interacting loci. However, recent advances on fungal spore killers reveal that numerous systems are enacted by single genes, and similar molecular genetic studies in Drosophila pinpoint individual loci that distort gamete sex. Notably, many meiotic drivers duplicate readily, forming gene families that can have complex interactions within and between species, and providing substrates for their rapid functional diversification. Here, we summarize the known families of meiotic drivers in fungi and fruit flies, and highlight shared principles about their evolution and proliferation that promote the spread of these noxious genes.
Paternal genome elimination: patterns and mechanisms of drive and silencing
27577M. Herbette and L. Ross, Current Opinion in Genetics and Development, 81. 2023-08-04 08:05:27.
In thousands of arthropod species, males inherit, but subsequently eliminate the entire haploid genome of their father. However, why this peculiar reproductive strategy evolved repeatedly across diverse species and what mechanisms are involved in paternal genome elimination (PGE) remains largely unknown. In this review, we summarize what we know about the patterns of paternal chromosome elimination during various stages of development in the diverse taxa that have been studied. We also discuss some other unusual features often associated with PGE, such as the transcriptional silencing of paternally derived chromosomes in males and sex determination through the early embryonic elimination of X chromosomes. Little is known about the molecular mechanisms underlying the parent-of-origin-dependent chromosome elimination and silencing under PGE, but we discuss the insight of several studies that are pioneering this work and highlight directions for future research.
Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis
27561H. Lee, P. Seo, S. Teklay, E. Yuguchi, E. D. Benetta, J. H. Werren and P. M. Ferree, Heredity, 2023-07-31 07:06:11.
B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR's own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp's genome also seem to evade chromatin disruption by PSR, suggesting that PSR's genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.
X chromosome drive is constrained by sexual selection and influences ornament evolution
27304K. A. Paczolt, G. T. Welsh and G. S. Wilkinson, Proceedings of the Royal Society B: Biological Sciences, 290:20230929. 2023-07-26 07:17:43.
Experimental evolution provides an integrative method for revealing complex interactions among evolutionary processes. One such interaction involves sex-linked selfish genetic elements and sexual selection. X-linked segregation distorters, a type of selfish genetic element, influence sperm transmission to increase in frequency and consequently alter the population sex ratio and the opportunity for sexual selection, while sexual selection may impact the spread of X-linked distorters. Here we manipulated sexual selection by controlling female mating opportunities and the presence of a distorting X chromosome in experimental lines of the stalk-eyed fly, Teleopsis dalmanni, over 11 generations. We find that removal of sexual selection leads to an increase in the frequency of the X-linked distorter and sex ratio across generations and that post-copulatory sexual selection alone is sufficient to limit the frequency of distorters. In addition, we find that male eyestalk length, a trait under pre-copulatory sexual selection, evolves in response to changes in the strength of sexual selection with the magnitude of the response dependent on X chromosome type and the frequency of distorting X chromosomes. These results reveal how a selfish X can interact with sexual selection to influence the evolution of sexually selected traits in multiple ways.
A natural gene drive system confers reproductive isolation in rice
27420C. Wang, J. Wang, J. Lu, Y. Xiong, Z. Zhao, X. Yu, X. Zheng, J. Li, Q. Lin, Y. Ren, Y. Hu, X. He, C. Li, Y. Zeng, R. Miao, M. Guo, B. Zhang, Y. Zhu, Y. Zhang, W. Tang, Y. Wang, B. Hao, Q. Wang, S. Cheng, X. He, B. Yao, J. Gao, X. Zhu, H. Yu, Y. Wang, Y. S, Cell, 2023-07-20 08:38:37.
Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two genes (iORF3/DUYAO and iORF4/JIEYAO) that confer preferential transmission of the RHS12-i type male gamete into the progeny, thereby forming a natural gene drive. DUYAO encodes a mitochondrion-targeted protein that interacts with OsCOX11 to trigger cytotoxicity and cell death, whereas JIEYAO encodes a protein that reroutes DUYAO to the autophagosome for degradation via direct physical interaction, thereby detoxifying DUYAO. Evolutionary trajectory analysis reveals that this system likely formed de novo in the AA genome Oryza clade and contributed to reproductive isolation (RI) between different lineages of rice. Our combined results provide mechanistic insights into the genetic basis of RI as well as insights for strategic designs of hybrid rice breeding.
Teosinte Pollen Drive guides maize domestication and evolution by RNAi
27414B. Berube , E. Ernst, J. Cahn, B. Roche, C. d. S. Alves, A. Scheben, A. Siepel, J. Ross-Ibarra, J. Kermicle and R. Martienssen, bioRxiv, 2023.07.12.548689. 2023-07-13 08:27:36.
Meiotic drivers subvert Mendelian expectations by manipulating reproductive development to bias their own transmission. Chromosomal drive typically functions in asymmetric female meiosis, while gene drive is normally postmeiotic and typically found in males. Using single molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Zea mays ssp. mexicana), that depends on RNA interference (RNAi). 22nt small RNAs from a non-coding RNA hairpin in mexicana depend on Dicer-Like 2 (Dcl2) and target Teosinte Drive Responder 1 (Tdr1), which encodes a lipase required for pollen viability. Dcl2, Tdr1, and the hairpin are in tight pseudolinkage on chromosome 5, but only when transmitted through the male. Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize. A survey of maize landraces and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least 3 chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive likely played a major role in maize domestication and evolution, and offers an explanation for the widespread abundance of "self" small RNAs in the germlines of plants and animals.Competing Interest StatementThe authors have declared no competing interest.
Unravelling transmission ratio distortion across the bovine genome: identification of candidate regions for reproduction defects
26542S. Id-Lahoucine, J. Casellas, A. Suárez-Vega, P. A. S. Fonseca, F. S. Schenkel, M. Sargolzaei and A. Cánovas, BMC Genomics, 24:383. 2023-07-08 08:21:35.
Our results revealed the importance of implementing different TRD parameterizations to capture all types of distortions and to determine the corresponding inheritance pattern. Novel candidate genomic regions containing lethal alleles and genes with functional and biological consequences on fertility and pre‑ and post‑natal viability were also identified, providing opportunities for improving breeding success in cattle
The evolutionary history of Drosophila simulans Y chromosomes reveals molecular signatures of resistance to sex ratio meiotic drive
26469C. Courret, D. Ogereau, C. Gilbert, A. M. Larracuente and C. Montchamp-Moreau, Mol Biol Evol, 2023-07-04 07:54:47.
The recent evolutionary history of the Y chromosome in Drosophila simulans, a worldwide species of Afrotropical origin, is closely linked to that of X-linked meiotic drivers (Paris system). The spread of the Paris drivers in natural populations has elicited the selection of drive resistant Y chromosomes. To infer the evolutionary history of the Y chromosome in relation to the Paris drive, we sequenced 21 iso-Y lines, each carrying a Y chromosome from a different location. Among them, 13 lines carry a Y chromosome that is able to counteract the effect of the drivers. Despite their very different geographical origins, all sensitive Y's are highly similar, suggesting that they share a recent common ancestor. The resistant Y chromosomes are more divergent and segregate in four distinct clusters. The phylogeny of the Y chromosome confirms that the resistant lineage predates the emergence of Paris drive. The ancestry of the resistant lineage is further supported by the examination of Y-linked sequences in the sister species of D. simulans, D. sechellia, and D. mauritiana. We also characterized the variation in repeat content among Y chromosomes and identified multiple simple satellites associated with resistance. Altogether, the molecular polymorphism allows us to infer the demographic and evolutionary history of the Y chromosome and provides new insights on the genetic basis of resistance.
Meiotic drive of noncentromeric loci in mammalian meiosis II eggs
26477D. M. Silva and T. Akera, Curr Opin Genet Dev, 81:102082. 2023-07-03 08:21:48.
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
Impacts of sex ratio meiotic drive on genome structure and function in a stalk-eyed fly
26279J. A. Reinhardt, R. H. Baker, A. V. Zimin, C. Ladias, K. A. Paczolt, J. H. Werren, C. Y. Hayashi and G. S. Wilkinson, Genome Biology Evolution, 2023-06-26 10:49:44.
Stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio meiotic drive (SR) and impact the fitness of male and female carriers. Here, we assemble and describe a chromosome-level genome assembly of the stalk-eyed fly, Teleopsis dalmanni, to elucidate patterns of divergence associated with SR. The genome contains tens of thousands of transposable element (TE) insertions and hundreds of transcriptionally and insertionally active TE families. By resequencing pools of SR and ST males using short and long-reads, we find widespread differentiation and divergence between XSR and XST associated with multiple nested inversions involving most of the sex ratio haplotype. Examination of genomic coverage and gene expression data revealed seven X-linked genes with elevated expression and coverage in SR males. The most extreme and likely drive candidate involves an XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and associated with regulation of TE expression. In addition, we find evidence for rapid protein evolution between XSR and XST for testis expressed and novel genes, i.e. either recent duplicates or lacking a dipteran ortholog, including an X-linked duplicate of maelstrom, which is also involved in TE silencing. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.
Do sex-linked male meiotic drivers contribute to intrinsic hybrid incompatibilities? Recent empirical studies from flies and rodents
26254J. Kitano and K. Yoshida, Current Opinion in Genetics and Development, 81:102068. 2023-06-22 08:05:04.
Intrinsic hybrid incompatibility is one of the important isolating barriers between species. In organisms with sex chromosomes, intrinsic hybrid incompatibility often follows two rules: Haldane’s rule and large-X effects. One explanation for these two rules is that sex chromosomes are hotspots for meiotic drivers that can cause intrinsic hybrid incompatibility between geographically isolated populations. Although this hypothesis seems plausible and several empirical data are consistent with it, we are still unsure whether such mechanisms occur in nature, particularly with respect to speciation with gene flow. Here, we review empirical studies that have investigated the roles of meiotic drive in sex-chromosome evolution and speciation and propose future studies necessary for testing this hypothesis.
Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
26252J. Vedanayagam, C. J. Lin, R. Papareddy, M. Nodine, A. S. Flynt, J. Wen and E. C. Lai, PLOS Genetics, 19:e1010787. 2023-06-21 07:57:17.
Although the biological utilities of endogenous RNAi (endo-RNAi) have been largely elusive, recent studies reveal its critical role in the non-model fruitfly Drosophila simulans to suppress selfish genes, whose unchecked activities can severely impair spermatogenesis. In particular, hairpin RNA (hpRNA) loci generate endo-siRNAs that suppress evolutionary novel, X-linked, meiotic drive loci. The consequences of deleting even a single hpRNA (Nmy) in males are profound, as such individuals are nearly incapable of siring male progeny. Here, comparative genomic analyses of D. simulans and D. melanogaster mutants of the core RNAi factor dcr-2 reveal a substantially expanded network of recently-emerged hpRNA-target interactions in the former species. The de novo hpRNA regulatory network in D. simulans provides insight into molecular strategies that underlie hpRNA emergence and their potential roles in sex chromosome conflict. In particular, our data support the existence of ongoing rapid evolution of Nmy/Dox-related networks, and recurrent targeting of testis HMG Box loci by hpRNAs. Importantly, the impact of the endo-RNAi network on gene expression flips the convention for regulatory networks, since we observe strong derepression of targets of the youngest hpRNAs, but only mild effects on the targets of the oldest hpRNAs. These data suggest that endo-RNAi are especially critical during incipient stages of intrinsic sex chromosome conflicts, and that continual cycles of distortion and resolution may contribute to speciation.
Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
25708J. Vedanayagam, M. Herbette, H. Mudgett, C. J. Lin, C. M. Lai, C. McDonough-Goldstein, S. Dorus, B. Loppin, C. Meiklejohn, R. Dubruille and E. C. Lai, PLoS Biol, 21:e3002136. 2023-06-08 10:27:14.
Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine-derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis.
Probing “Selfish” Centromeres Unveils an Evolutionary Arms Race
24935M. Lampson, The Scientist, 2023-04-03 10:08:47.
The so-called Robertsonian (Rb) fusions that led to these rapid karyotype changes are relatively common chromosomal rearrangements. But their accumulation in the populations of Madeira Island and in multiple other isolated mouse populations elsewhere is likely due to another influencing factor: the preferential segregation of the Rb fusion into the egg rather than into the discarded polar bodies that form during female meiosis. We usually think of the chromosome segregation machinery as ensuring unbiased, random segregation. As we learn in high school biology, if a diploid individual carries two different alleles of a gene (i.e., is heterozygous), then either allele is equally likely to end up in a haploid gamete. This law explains the 3:1 ratio of phenotypes that Mendel observed in his classic studies of heredity. Scientists have known for decades, however, that selfish genes can subvert Mendelian segregation to increase their frequency in the next generation, a phenomenon known as meiotic drive. The Madeira mice suggest that fusion chromosomes can also drive unequal inheritance.
Synthetic gene drives as an anthropogenic evolutionary force
24895A. D. Cutter, Trends in Genetics, 2023-03-28 07:24:22.
Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of ‘genetic welding’ as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection. Genetic welding is capable of imposing complex and rapid heritable phenotypic change on entire populations, whether motivated by biodiversity conservation or public health. Unanticipated possible long-term evolutionary outcomes, however, demand further investigation and bioethical consideration. The emerging importance of genetic welding also compels our explicit recognition of genetic drive as an addition to the other four fundamental forces of evolution.
Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes
24732C.-H. Chang, I. Mejia Natividad and H. S. Malik, eLife, 12:e85249. 2023-02-10 09:47:51.
Many animal species employ sperm nuclear basic proteins (SNBPs) or protamines to package sperm genomes tightly. SNBPs vary across animal lineages and evolve rapidly in mammals. We used a phylogenomic approach to investigate SNBP diversification in Drosophila species. We found that most SNBP genes in Drosophila melanogaster evolve under positive selection except for genes essential for male fertility. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved SNBP genes. For example, CG30056 is dispensable for male fertility despite being one of three SNBP genes universally retained in Drosophila species. We found 19 independent SNBP gene amplification events that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved SNBP genes, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions were more likely to degenerate or relocate back to autosomes. We hypothesize that autosomal SNBP genes suppress meiotic drive, whereas sex-chromosomal SNBP expansions lead to meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, genetic conflicts between sex chromosomes may drive SNBP rapid evolution during spermatogenesis in Drosophila species.
A selfish genetic element and its suppressor causes gross damage to testes in a fly
24697S. Lyth, A. Manser, G. Hurst, T. Price and R. Verspoor, bioRxiv, 2023.02.06.527273. 2023-02-06 12:34:06.
Selfish genetic elements (SGEs), specifically X-chromosome meiotic drive (XCMD), create huge conflicts within a hosts genome and can have profound effects on fertility. Suppressors are a common evolutionary response to XCMD to negate its costs. However, whether suppressors themselves can cause negative non-target effects remains understudied. Here, we examine whether the intragenomic conflicts created by XCMD and its suppressor affects gonad morphology in Drosophila subobscura. We found significant differences in testes, seminal vesicle, and accessory gland size depending on whether a male carried a non-driving X chromosome, an XCMD, and if the XCMD was suppressed. We also found the first evidence of extreme whole-organ damage to testes that is specifically associated with a suppressor of XCMD. Unlike other studies, our evidence suggests that XCMD in D. subobscura inflicts extreme damage on male gonads. This damage is most severe if both XCMD and its suppressor are both present. While costs of suppression have importance in theoretical models, they have largely been ignored in empirical XCMD systems. Overall, this study highlights that genetic conflict, created by SGEs and their suppressors, is a potent evolutionary force that can have major impacts on gonad development and gametogenesis.Competing Interest StatementThe authors have declared no competing interest.
Both male and female meiosis contribute to non-Mendelian inheritance of parental chromosomes in interspecific plant hybrids (Lolium x Festuca)
24833J. Majka, M. Glombik, A. Dolezalova, J. Knerova, M. T. M. Ferreira, Z. Zwierzykowski, M. Duchoslav, B. Studer, J. Dolezel, J. Bartos and D. Kopecky, NEW PHYTOLOGIST, 2023-01-19 08:34:11.
Some interspecific plant hybrids show unequal transmission of chromosomes from parental genomes to the successive generations. It has been suggested that this is due to a differential behavior of parental chromosomes during meiosis. However, underlying mechanism is unknown. We analyzed chromosome composition of the F-2 generation of Festuca x Lolium hybrids and reciprocal backcrosses to elucidate effects of male and female meiosis on the shift in parental genome composition. We studied male meiosis, including the attachment of chromosomes to the karyokinetic spindle and gene expression profiling of the kinetochore genes. We found that Lolium and Festuca homoeologues were transmitted differently to the F-2 generation. Female meiosis led to the replacement of Festuca chromosomes by their Lolium counterparts. In male meiosis, Festuca univalents were attached less frequently to microtubules than Lolium univalents, lagged in divisions and formed micronuclei, which were subsequently eliminated. Genome sequence analysis revealed a number of non-synonymous mutations between copies of the kinetochore genes from Festuca and Lolium genomes. Furthermore, we found that outer kinetochore proteins NDC80 and NNF1 were exclusively expressed from the Lolium allele. We hypothesize that silencing of Festuca alleles results in improper attachment of Festuca chromosomes to karyokinetic spindle and subsequently their gradual elimination.
Bypassing Mendel’s First Law: Transmission Ratio Distortion in Mammals
24587G. Friocourt, A. Perrin, P. A. Saunders, E. Nikalayevich, C. Voisset, C. Coutton, G. Martinez and F. Morel, International Journal Molecular Sciences, 24. 2023-01-13 10:43:58.
Mendel's law of segregation states that the two alleles at a diploid locus should be transmitted equally to the progeny. A genetic segregation distortion, also referred to as transmission ratio distortion (TRD), is a statistically significant deviation from this rule. TRD has been observed in several mammal species and may be due to different biological mechanisms occurring at diverse time points ranging from gamete formation to lethality at post-natal stages. In this review, we describe examples of TRD and their possible mechanisms in mammals based on current knowledge. We first focus on the differences between TRD in male and female gametogenesis in the house mouse, in which some of the most well studied TRD systems have been characterized. We then describe known TRD in other mammals, with a special focus on the farmed species and in the peculiar common shrew species. Finally, we discuss TRD in human diseases. Thus far, to our knowledge, this is the first time that such description is proposed. This review will help better comprehend the processes involved in TRD. A better understanding of these molecular mechanisms will imply a better comprehension of their impact on fertility and on genome evolution. In turn, this should allow for better genetic counseling and lead to better care for human families.
How Selfish Genes Succeed: Critical Insights Uncovered About Dangerous DNA
24318STOWERS INSTITUTE FOR MEDICAL RESEARCH, SciTechDaily, 2022-12-22 08:48:15.
New findings from the Stowers Institute for Medical Research uncover critical insights about how a dangerous selfish gene—considered to be a parasitic portion of DNA—functions and survives. Understanding this dynamic is a valuable resource for the broader community studying meiotic drive systems. A new study, published in PLoS Genetics on December 7, 2022, reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are designing synthetic drive systems for pathogenic pest control. Collective and collaborative advancement in understanding drive may one day lead to the eradication of pest populations that harm crops or even humans in the case of vector-borne diseases.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
How selfish genes succeed
24155Stowers Institute for Medical Research, ScienceDaily, 2022-12-08 07:17:01.
A new study reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are designing synthetic drive systems for pathogenic pest control. Collective and collaborative advancement on understanding drive may one day lead to the eradication of pest populations that harm crops or even humans in the case of vector borne diseases.
S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive
24158N. L. Nuckolls, A. Nidamangala Srinivasa, A. C. Mok, R. M. Helston, M. A. Bravo Núñez, J. J. Lange, T. J. Gallagher, C. W. Seidel and S. E. Zanders, PLOS Genetics, 18:e1009847. 2022-12-07 07:23:14.
Author summary Genomes are often considered a collection of ‘good’ genes that provide beneficial functions for the organism. From this perspective, disease is thought to arise due to disfunction of ‘good’ genes. For example, infertility can be caused by the failure of a gene that normally helps fertility. This view is incomplete as ‘parasitic’ genes that provide no benefit to the organism also exist. These genes can also contribute to disease, often as a result of the mechanisms they use to ensure their transmission to the next generation. For example, killer meiotic drivers are found throughout eukaryotes and contribute to infertility by actively destroying the gametes (e.g., egg and sperm) that do not inherit them. In this work we study the transcriptional regulation of wtf4, a model killer meiotic driver found in fission yeast to understand mechanisms of drive. The wtf4 gene encodes both a poison and an antidote protein on largely overlapping coding sequences. We found that different promoters and differential localization properties of the poison and antidote proteins both facilitate killer meiotic drive. We also found that the expression of the poison protein relies on a key transcription factor essential for gametogenesis. The use of this transcription factor likely complicates suppressing wtf4 without compromising gametogenesis. This feature likely contributes to the evolutionary success of the wtf drivers, which are found in many copies in fission yeast genomes.
A natural gene drive could steer invasive rodents on islands to extinction
24129B. Brookshire, ScienceNews, 2022-12-05 09:12:58.
In the battle against the invasive house mouse on islands, scientists are using the rodent’s own genes against it. With the right tweaks, introducing a few hundred genetically altered mice could drive an island’s invasive mouse population to extinction in about 25 years, researchers report in the Nov. 15 Proceedings of the National Academy of Sciences. The trick is adding the changes to a section of mouse DNA that gets inherited far more often than it should. Scientists have been creating similar extra-inheritable genes — called gene drives — in the lab. The chunks are designed to get passed on to most or all of an animal’s offspring instead of the usual half, and make those offspring infertile in the bargain. Scientists have used gene drives to reduce populations of mosquitoes and fruit flies (SN: 12/17/18). But mammals are a different story. Scientists have previously synthesized a gene drive that gets passed on in mice about 80 percent of the time (SN: 1/23/19). But the drive isn’t strong enough to stop a population quickly. Luckily, nature has it handled. A haplotype is a naturally occurring group of genes that gets passed on as a unit during replication. The genome of the house mouse (Mus musculus) has a particular haplotype, called the t haplotype, that gets passed on to offspring more than 95 percent of the time, instead of the typical 50 percent.
Deregulation of Y-linked protamine-like genes in sex chromosome-biased spermatid demise
24124J. I. Park, G. W. Bell and Y. M. Yamashita, bioRxiv, 2022-12-05 08:57:46.
Meiotic drive is a phenomenon wherein a genetic element achieves a higher rate of transmission than dictated by Mendelian segregation (1-3). One proposed mechanism for meiotic drivers to achieve biased transmission is by sabotaging essential processes of gametogenesis (e.g. spermatogenesis), leading to demise of gametes that contain their opponents (1). Studies in D. simulans have recently found that a set of meiotic driver genes contain a sequence homologous to protamines (4, 5), critical proteins that package sperm chromatin (6-8). However, the underlying mechanisms of drive and the relevance of protamine-like sequences in meiotic drive remain unknown. While studying the function of Modulo, the homolog of Nucleolin in Drosophila melanogaster (9, 10), we unexpectedly discovered Y-linked protamine genes function as a meiotic driver: we found that modulo mutant's known sterility is caused by deregulation of the autosomal protamine-like gene (Mst77F) and its Y chromosome-linked homolog (Mst77Y). Modulo regulates these genes at the step of polyadenylation of the transcripts. We show that Mst77Y likely acts as a dominant-negative form of Mst77F, interfering with the process of histone-to-protamine transition, leading to nuclear decompaction. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear decompaction and results in the biased demise of X chromosome-bearing sperm. We propose that dominant-negative protamine variants may be a common strategy found in male meiotic drive and may explain known rapid divergence of protamine genes.Competing Interest StatementThe authors have declared no competing interest.
Meiotic transmission patterns of additional genomic elements in Brachionus asplanchnoidis, a rotifer with intraspecific genome size variation
24116J. Blommaert and C.-P. Stelzer, Scientific Reports, 12:20900. 2022-12-03 09:37:14.
Intraspecific genome size (GS) variation in Eukaryotes is often mediated by additional, nonessential genomic elements. Physically, such additional elements may be represented by supernumerary (B-)chromosomes or by large heterozygous insertions into the regular chromosome set. Here we analyze meiotic transmission patterns of Megabase-sized, independently segregating genomic elements (ISEs) in Brachionus asplanchnoidis, a planktonic rotifer that displays an up to two-fold intraspecific GS variation due to variation in size and number of these elements. To gain insights into the meiotic transmission patterns of ISEs, we measured GS distributions of haploid males produced by individual mother clones using flow cytometry and compared these distributions to theoretical distributions expected under a range of scenarios. These scenarios considered transmission biases resembling (meiotic) drive, or cosegregation biases, e.g., if pairs of ISEs preferentially migrated towards the same pole during meiosis. We found that the inferred transmission patterns were diverse and ranged from positive biases (suggesting drive) to negative biases (suggesting drag), depending on rotifer clone and its ISE composition. Additionally, we obtained evidence for a negative cosegregation bias in some of the rotifer clones, i.e., pairs of ISEs exhibited an increased probability of migrating towards opposite poles during meiosis. Strikingly, these transmission and segregation patterns were more similar among members of a genetically homogeneous inbred line than among outbred members of the population. Comparisons between early and late stages of haploid male embryonic development (e.g., young synchronized male eggs vs. hatched males) showed very similar GS distributions, suggesting that transmission biases occur very early in male development, or even during meiosis. Very large genome size was associated with reduced male embryonic survival, suggesting that excessive amounts of ISEs might be detrimental to male fitness. Altogether, our results indicate considerable functional diversity of ISEs in B. asplanchnoidis, with consequences on meiotic transmission and embryonic survival.
Meiotic drive adaptive testes enlargement during early development in the stalk-eyed fly
24087S. L. Bradshaw, L. Meade, J. Tarlton-Weatherall and A. Pomiankowski, Biology Letters, 18:20220352. 2022-11-30 09:02:09.
The sex ratio (SR) X-linked meiotic drive system in stalk-eyed flies destroys Y-bearing sperm. Unlike other SR systems, drive males do not suffer fertility loss. They have greatly enlarged testes which compensate for gamete killing. We predicted that enlarged testes arise from extended development with resources re-allocated from the accessory glands, as these tend to be smaller in drive males. To test this, we tracked the growth of the testes and accessory glands of wild-type and drive males over 5-6 weeks post-eclosion before males attained sexual maturity. Neither of the original predictions is supported by these data. Instead, we found that the drive male testes were enlarged at eclosion, reflecting a greater allocation of resources to the testes during pupation. Testes grow at a higher rate during early adult development in drive males, but there was no evidence that this retards the growth of the accessory glands. Further experiments are proposed to investigate whether smaller accessory glands only arise in drive males post-copulation or when flies are subjected to nutritional stress. Our experimental findings support the idea that enlarged testes in drive males arise as an adaptive allocation of resources to traits that enhance male reproductive success.
Discovery of 119-Million-Year-Old “Selfish” Genes Casts Doubt on Established Evolution Beliefs
24042Stowers Institute for Medical Research, SciTechDaily, 2022-11-23 10:50:53.
Meiotic drivers, a kind of selfish gene, are indeed selfish. They are found in virtually all species’ genomes, including humans, and unjustly transfer their genetic material to more than half of their offspring, resulting in infertility and impaired organism health. Their longevity over evolutionary time was thought to be brief due to their parasitic potential, until recently. The Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has discovered a selfish gene family that has survived for over 100 million years—ten times longer than any other meiotic driver ever identified—calling into question established beliefs about how natural selection and evolution deal with these threatening sequences.
Discovery of 119-Million year old Selfish Genes Casts Doubt on Established Evolution Beliefs
24039Stowers Institute for Medical Research, 2022-11-23 10:39:51.
Meiotic drivers, a kind of selfish gene, are indeed selfish. They are found in virtually all species’ genomes, including humans, and unjustly transfer their genetic material to more than half of their offspring, resulting in infertility and impaired organism health. Their longevity over evolutionary time was thought to be brief due to their parasitic potential, until recently. The Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has discovered a selfish gene family that has survived for over 100 million years—ten times longer than any other meiotic driver ever identified—calling into question established beliefs about how natural selection and evolution deal with these threatening sequences.
Driving lessons: a brief (personal) history of centromere drive
24030H. S. Malik, Genetics, 2022-11-15 09:41:41.
Meiosis is an important specialized cell division in many eukaryotic species, including fungi, plants, and animals. Meiosis results in the production of haploid gametes starting from a diploid cell via 1 round of replication and 2 rounds of cell division. In an influential article published in 1957, Sandler and Novitski first pointed out that meiosis is also an intense battleground, in which gametes vie for evolutionary supremacy with each other, often poisoning their competition to gain a fratricidal advantage (Sandler and Novitski 1957). This competition, which they termed “meiotic drive,” operates as an evolutionary force that can cause an increase in frequency of the allele that is favored during meiotic transmission. Unlike alleles that rise in frequency because they confer a fitness advantage to their carriers, meiotic drivers can rise in frequency even while conferring significant fitness disadvantages on their carriers. Thus, meiotic drivers can be viewed as the quintessential selfish genes; it is the best interest of the rest of the genome to counteract their action to restore organismal fitness.
Centromere drive: chromatin conflict in meiosis
23856P. Talbert and S. Henikoff, Current Opinion in Genetics and Development, 77:102005. 2022-11-11 10:41:54.
Centromeres are essential loci in eukaryotes that are necessary for the faithful segregation of chromosomes in mitosis and meiosis. Centromeres organize the kinetochore, the protein machine that attaches sister chromatids or homologous chromosomes to spindle microtubules and regulates their disjunction. Centromeres have both genetic and epigenetic determinants, which can come into conflict in asymmetric female meiosis in seed plants and animals. The centromere drive model was proposed to describe this conflict and explain how it leads to the rapid evolution of both centromeres and kinetochores. Recent studies confirm key aspects of the centromere drive model, clarify its mechanisms, and implicate rapid centromere/kinetochore evolution in hybrid inviability between species.
Gene drive could be used to wipe out invasive mice on islands
23862M. Le Page, NewScientist, 2022-11-11 10:11:35.
For the first time, researchers have created a gene drive – a kind of genetic parasite – that could be used to eradicate mammalian pests such as mice by making them infertile. The technology could provide a humane alternative to the poison baits currently used to tackle invasive mice on islands, which have severe impacts on native birds, reptiles and plants. “It’s the first example of a mammalian gene drive technology that has had proof of concept in a laboratory setting,” says Paul Thomas at the University of Adelaide in Australia. Most animals have two copies of each chromosome, but their offspring gets only one copy from each parent. This means that if a piece of DNA is added to one chromosome of an individual, only half its offspring will inherit it. Gene drives are bits of DNA that encode various mechanisms for cheating the system and ensuring they get inherited by more than half of offspring. This means they can spread in a population even if they are harmful. Various kinds of natural gene drives have been discovered. In 2013, Kevin Esvelt at Massachusetts Institute of Technology created the first synthetic gene drive using the gene-editing technology CRISPR. Such CRISPR-based gene drives work extremely well in insects and several teams hope to use them to prevent the spread of malaria, either by wiping out mosquitoes or by making them less likely to infect people.
World first trial to eradicate mice through gene modification
23838I. Mannix, COSMOS, 2022-11-10 09:51:29.
Mouse populations could be eradicated in some areas through new gene modification technology to render female mice infertile. The technology – called t-CRISPR – was previously developed to target malaria-transmitting mosquitoes. This is the first proof of concept for its use as a mammalian genetic biocontrol tool targeting house mice, which is an invasive pest in Australia. In time, it could be used to control rodents on islands and landmasses where they cause widespread destruction. The research, published in Proceedings of the National Academy of Sciences, is the first time t-CRISPR has been successfully tested on mammals in a laboratory setting, according to senior author Professor Paul Thomas. Computer modelling conducted by the team suggests about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. “We have had mouse plagues in Australia for 150 years and existing controls, like baits, cause inhumane death and are expensive and labour intensive to deploy,” says Thomas, who works across the University of Adelaide and the South Australian Health and Medical Research Institute.
Leveraging a natural murine meiotic drive to suppress invasive populations
23835L. Gierus, A. Birand, M. D. Bunting, G. I. Godahewa, S. G. Piltz, K. P. Oh, A. J. Piaggio, D. W. Threadgill, J. Godwin, O. Edwards, P. Cassey, J. V. Ross, T. A. A. Prowse and P. Q. Thomas, Proceedings of the National Academy of Sciences, 119:e2213308119. 2022-11-08 09:36:13.
Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (t(CRISPR)) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that t(CRISPR) can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic t(CRISPR) mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.
119-Million-Year-Old “Selfish” Genes Uncovered in Yeast
23785Stowers Institute for Medical Research, Technology Networks, 2022-10-19 07:15:07.
Meiotic drivers, a type of selfish gene, are indeed selfish. Present in the genomes of nearly all species, including humans, they unfairly transfer their genetic material to more than half of their offspring, sometimes leading to infertility, and decreased organism health. Because of their parasitic potential, their longevity over evolutionary time is believed to be short-lived, until now. New research from the Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has uncovered a selfish gene family that has survived for over 100 million years—10 times longer than any meiotic driver ever identified—casting new doubt on established beliefs on how natural selection and evolution tackle these threatening sequences.
The wtf meiotic driver gene family has unexpectedly persisted for over 100 million years
23712M. De Carvalho, G. S. Jia, A. Nidamangala Srinivasa, R. B. Billmyre, Y. H. Xu, J. J. Lange, I. M. Sabbarini, L. L. Du and S. E. Zanders, eLife, 11. 2022-10-13 06:23:07.
Meiotic drivers are selfish elements that bias their own transmission into more than half of the viable progeny produced by a driver+/driver- heterozygote. Meiotic drivers are thought to exist for relatively short evolutionary timespans because a driver gene or gene family is often found in a single species or in a group of very closely related species. Additionally, drivers are generally considered doomed to extinction when they spread to fixation or when suppressors arise. In this study, we examine the evolutionary history of the wtf meiotic drivers first discovered in the fission yeast Schizosaccharomyces pombe. We identify homologous genes in three other fission yeast species, S. octosporus, S. osmophilus, and S. cryophilus, which are estimated to have diverged over 100 million years ago from the S. pombe lineage. Synteny evidence supports that wtf genes were present in the common ancestor of these four species. Moreover, the ancestral genes were likely drivers as wtf genes in S. octosporus cause meiotic drive. Our findings indicate that meiotic drive systems can be maintained for long evolutionary timespans.
Meiotic defects in human oocytes: Potential causes and clinical implications
23677T. Wu, H. Gu, Y. Luo, L. Wang and Q. Sang, BioEssays, 2022-10-07 08:30:48.
Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error-prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), and clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models.
Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura
23719S. Koury, G3 Genes|Genomes|Genetics, 2022-10-04 06:48:20.
Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with three non-overlapping inversions. In the male germline, Sex Ratio chromosomes distort segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but non-overlapping inversions strongly suppress recombination establishing a 26 Megabase haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between non-overlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals these recombination events were at least 4-fold more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26 Megabase Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally-occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
Meiotic drive is associated with sexual incompatibility in Neurospora
23613A. Vogan, J. Svedberg, M. Grudzinska-Sterno and H. Johannesson, Evolution, 2022-09-23 09:26:32.
Evolution of Bateson-Dobzhansky-Muller (BDM) incompatibilities is thought to represent a key step in the formation of separate species. They are incompatible alleles that have evolved in separate populations and are exposed in hybrid offspring as hybrid sterility or lethality. In this study we reveal a previously unconsidered mechanism promoting the formation of BDM incompatibilities, meiotic drive. Theoretical studies have evaluated the role that meiotic drive, the phenomenon whereby selfish elements bias their transmission to progeny at ratios above 50:50, plays in speciation, and have mostly concluded that drive could not result in speciation on its own. Using the model fungus Neurospora, we demonstrate that the large meiotic drive haplotypes, Sk-2 and Sk-3, contain putative sexual incompatibilities. Our experiments revealed that while crosses between N. intermedia and N. metzenbergii produce viable progeny at appreciable rates, when strains of N. intermedia carry Sk-2 or Sk-3 the proportion of viable progeny drops substantially. Additionally, it appears that Sk-2 and Sk-3 have accumulated different incompatibility phenotypes, consistent with their independent evolutionary history. This research illustrates how meiotic drive can contribute to reproductive isolation between populations, and thereby speciation. This article is protected by copyright. All rights reserved.
Meiotic drive does not impede success in sperm competition in the stalk-eyed fly, Teleopsis dalmanni
23566S. Bates, L. Meade and A. Pomiankowski, bioRxiv, 2022-09-13 15:00:24.
Meiotic drive genes are selfish genetic elements that distort Mendelian patterns of inheritance to bias transmission in their favour. We use the stalk-eyed fly, Teleopsis dalmanni, to investigate the fitness effects associated with a meiotic drive gene called Sex Ratio (SR), which is linked to the X chromosome. In males, SR destroys Y-bearing sperm, meaning only X-bearing sperm are viable, and females who mate with drive males sire all-female broods. This confers a two-fold transmission advantage to the SR gene, as it is transmitted to all offspring.We recently discovered that drive males have evolved compensatory mechanisms to cope with the sperm destruction caused by meiotic drive. They have greatly enlarged testes, allowing them to produce more sperm. When drive males mate with females, they deliver as many sperm and sire as many offspring as wildtype males. Building on this finding, we measured how drive male sperm performs against sperm from a non-carrier male in sperm competition – where the sperm from different males compete to fertilise an egg. Double mating trials were performed, where a single female was mated once to a drive and once to a non-carrier male. By genotyping offspring, we show that the number of offspring sired by the drive male was not different from the number sired by the non-carrier competitor.These findings contrast with those in other species. Typically, drive males do poorly in sperm competition and their spread is severely restricted by sperm competition. In stalk-eyed flies, female multiple mating with many males is the norm, but this does not appear to inhibit the fertility of drive males. The success of drive under sperm competition helps to explain the high frequency of drive around 20% in natural populations of T. dalmanni.Competing Interest StatementThe authors have declared no competing interest.
Enforcement of Postzygotic Species Boundaries in the Fungal Kingdom
23560J. Y. Chou, P. C. Hsu and J. Y. Leu, Microbiology and Molecular Biology Reviews, 2022-09-13 14:48:04.
Understanding the molecular basis of speciation is a primary goal in evolutionary biology. The formation of the postzygotic reproductive isolation that causes hybrid dysfunction, thereby reducing gene flow between diverging populations, is crucial for speciation. Using various advanced approaches, including chromosome replacement, hybrid introgression and transcriptomics, population genomics, and experimental evolution, scientists have revealed multiple mechanisms involved in postzygotic barriers in the fungal kingdom. These results illuminate both unique and general features of fungal speciation. Our review summarizes experiments on fungi exploring how Dobzhansky-Muller incompatibility, killer meiotic drive, chromosome rearrangements, and antirecombination contribute to postzygotic reproductive isolation. We also discuss possible evolutionary forces underlying different reproductive isolation mechanisms and the potential roles of the evolutionary arms race under the Red Queen hypothesis and epigenetic divergence in speciation.
On the Mechanistic Basis of Killer Meiotic Drive in Fungi
23530S. J. Saupe and H. Johannesson, Annual Review of Microbiology, 76:305-323. 2022-09-08 05:38:51.
Spore killers are specific genetic elements in fungi that kill sexual spores that do not contain them. A range of studies in the last few years have provided the long-awaited first insights into the molecular mechanistic aspects of spore killing in different fungal models, including both yeast-forming and filamentous Ascomycota. Here we describe these recent advances, focusing on the wtf system in the fission yeast Schizosaccharomyces pombe; the Sk spore killers of Neurospora species; and two spore-killer systems in Podospora anserina, Spok and [Het-s]. The spore killers appear thus far mechanistically unrelated. They can involve large genomic rearrangements but most often rely on the action of just a single gene. Data gathered so far show that the protein domains involved in the killing and resistance processes differ among the systems and are not homologous. The emerging picture sketched by these studies is thus one of great mechanistic and evolutionary diversity of elements that cheat during meiosis and are thereby preferentially inherited over sexual generations.
Hoisted with his own petard: How sex-ratio meiotic drive in Drosophila affinis creates resistance alleles that limit its spread
23471W. J. Ma, E. M. Knoles, K. B. Patch, M. M. Shoaib and R. L. Unckless, J Evol Biol, 2022-08-23 07:13:52.
Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons-effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome, and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.
Non-Mendelian transmission of accessory chromosomes in fungi
23305J. Komluski, E. H. Stukenbrock and M. Habig, Chromosome Research, 2022-07-26 07:44:07.
Non-Mendelian transmission has been reported for various genetic elements, ranging from small transposons to entire chromosomes. One prime example of such a transmission pattern are B chromosomes in plants and animals. Accessory chromosomes in fungi are similar to B chromosomes in showing presence/absence polymorphism and being non-essential. How these chromosomes are transmitted during meiosis is however poorly understood-despite their often high impact on the fitness of the host. For several fungal organisms, a non-Mendelian transmission or a mechanistically unique meiotic drive of accessory chromosomes have been reported. In this review, we provide an overview of the possible mechanisms that can cause the non-Mendelian transmission or meiotic drives of fungal accessory chromosomes. We compare processes responsible for the non-Mendelian transmission of accessory chromosomes for different fungal eukaryotes and discuss the structural traits of fungal accessory chromosomes affecting their meiotic transmission. We conclude that research on fungal accessory chromosomes, due to their small size, ease of sequencing, and epigenetic profiling, can complement the study of B chromosomes in deciphering factors that influence and regulate the non-Mendelian transmission of entire chromosomes.
“Selfish Genetic Elements” – Supergene Wreaks Havoc in a Genome
23302University of Rochester, SciTechDaily, 2022-07-25 07:37:40.
“Selfish genetic elements” litter the human genome. They do not seem to benefit their hosts but instead seek only to propagate themselves. These selfish genetic elements can wreak havoc. For example, they can distort sex ratios, impair fertility, cause harmful mutations, and even potentially cause population extinction. Biologists have for the first time used population genomics to shed light on the evolution and consequences of a selfish genetic element known as Segregation Distorter (SD). These researchers at the University of Rochester, include Amanda Larracuente, an associate professor of biology, and Daven Presgraves, a University Dean’s Professor of Biology. In a paper published recently in the journal eLife, the scientists report that SD has caused dramatic changes in chromosome organization and genetic diversity.
What can we learn from selfish loci that break Mendel’s law?
23349S. E. Zanders, PLOS Biology, 20:e3001700. 2022-07-19 07:31:24.
Mendel’s law of segregation provides a critical foundation for genetic inquiry It is not, however, without exceptions Historically, 2 such exceptions (sex chromosome linkage and chromosome missegregation in meiosis) were used by Drosophila geneticists to help demonstrate that genes are carried on chromosomes Looking forward, modern geneticists interested in understanding the mechanisms of heredity have much to learn from additional exceptions to Mendel’s law In particular, selfish genes that break Mendel’s law of segregation to gain a transmission advantage into the next generation are likely to be oversized contributors to shaping the process of sexual reproduction These selfish genes exploit reproduction such that a given selfish locus is transmitted to more than half of the offspring produced by an organism There are a variety of selfish DNAs, but here I will focus on transposable elements and drive loci as examples Transposable elements can generate novel copies of themselves using copy and paste or cut and paste mechanisms Importantly, transposable elements are selected to mobilize in the germline as that allows new copies to be passed on to subsequent generations Drive loci preferentially bias their own transmission such that a driver+ /driver− heterozygote will pass the driver+ allele to more than half of its viable progeny Drivers are diverse and can act during meiosis, gametogenesis, or post-fertilization Both transposable elements and drivers are found throughout eukaryotes, including humans
Adaptive meiotic drive in selfing populations with heterozygote advantage
23271E. Brud, Theoretical Population Biology, 146:61-70. 2022-07-13 07:46:37.
The egalitarian allotment of gametes to each allele at a locus (Mendel's law of segregation) is a near-universal phenomenon characterizing inheritance in sexual populations. As exceptions to Mendel's law are known to occur, one can investigate why non-Mendelian segregation is not more common using modifier theory. Earlier work assuming sex-independent modifier effects in a random mating population with heterozygote advantage concluded that equal segregation is stable over long-term evolution. Subsequent investigation, however, demonstrated that the stability of the Mendelian scheme disappears when sex-specific modifier effects are allowed. Here I derive invasion conditions favoring the repeal of Mendelian law in mixed and obligate selfing populations. Oppositely-directed segregation distortion in the production of male and female gametes is selected for in the presence of overdominant fitness. The conditions are less restrictive than under panmixia in that strong selection can occur even without differential viability of reciprocal heterozygotes (i.e. in the absence of parent-of-origin effects at the overdominant fitness locus). Generalized equilibria are derived for full selfing.
Meiotic drive in house mice: mechanisms, consequences, and insights for human biology
23233U. P. Arora and B. L. Dumont, Chromosome Research, 2022-07-13 06:38:49.
Meiotic drive occurs when one allele at a heterozygous site cheats its way into a disproportionate share of functional gametes, violating Mendel's law of equal segregation. This genetic conflict typically imposes a fitness cost to individuals, often by disrupting the process of gametogenesis. The evolutionary impact of meiotic drive is substantial, and the phenomenon has been associated with infertility and reproductive isolation in a wide range of organisms. However, cases of meiotic drive in humans remain elusive, a finding that likely reflects the inherent challenges of detecting drive in our species rather than unique features of human genome biology. Here, we make the case that house mice (Mus musculus) present a powerful model system to investigate the mechanisms and consequences of meiotic drive and facilitate translational inferences about the scope and potential mechanisms of drive in humans. We first detail how different house mouse resources have been harnessed to identify cases of meiotic drive and the underlying mechanisms utilized to override Mendel's rules of inheritance. We then summarize the current state of knowledge of meiotic drive in the mouse genome. We profile known mechanisms leading to transmission bias at several established drive elements. We discuss how a detailed understanding of meiotic drive in mice can steer the search for drive elements in our own species. Lastly, we conclude with a prospective look into how new technologies and molecular tools can help resolve lingering mysteries about the prevalence and mechanisms of selfish DNA transmission in mammals.
Mendel’s laws of heredity on his 200th birthday: What have we learned by considering exceptions?
23269J. B. Wolf, A. C. Ferguson-Smith and A. Lorenz, Heredity, 129:1-3. 2022-07-01 07:36:08.
Violations of Mendel’s laws can generically be referred to as ‘non-Mendelian inheritance’. However, from that broad perspective, nearly all inheritance systems would show non-Mendelian inheritance (at least to some degree). To hold exactly, Mendel’s laws impose strict requirements: a locus has to contain two allelic variants that have discrete effects on categorical (or at least discrete and countable) traits, and they must show complete dominance. These strict conditions are rarely met in real systems (Hou et al. 2016), both because allelic effects do not adhere to the strict law of dominance and because many traits of interest show continuous variation. Mendel recognised many of the exceptions related to effects of alleles, such as the presence of incomplete dominance, pleiotropy, and epistasis (see Fairbanks 2022, this volume), and Fisher (1918) reconciled the assumption of Mendelian inheritance with continuous variation. Hence, from this perspective, a large array of scenarios that show nonMendelian inheritance are actually consistent with the conceptual foundation of Mendel’s perspective based on elemental inheritance
Centromere drive: model systems and experimental progress
23148D. Dudka and M. A. Lampson, Chromosome Research, 2022-06-22 09:28:53.
Centromeres connect chromosomes and spindle microtubules to ensure faithful chromosome segregation. Paradoxically, despite this conserved function, centromeric DNA evolves rapidly and centromeric proteins show signatures of positive selection. The centromere drive hypothesis proposes that centromeric DNA can act like a selfish genetic element and drive non-Mendelian segregation during asymmetric female meiosis. Resulting fitness costs lead to genetic conflict with the rest of the genome and impose a selective pressure for centromeric proteins to adapt by suppressing the costs. Here, we describe experimental model systems for centromere drive in yellow monkeyflowers and mice, summarize key findings demonstrating centromere drive, and explain molecular mechanisms. We further discuss efforts to test if centromeric proteins are involved in suppressing drive-associated fitness costs, highlight a model for centromere drive and suppression in mice, and put forth outstanding questions for future research.
Hoisted with his own petard: how sex-ratio meiotic drive in <em>Drosophila affinis</em> creates resistance alleles that limit its spread
23231W.-J. Ma, E. M. Knoles, K. B. Patch, M. M. Shoaib and R. L. Unckless, bioRxiv, 2022.02.14.480432. 2022-06-19 06:28:31.
Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.Competing Interest StatementThe authors have declared no competing interest.
Natural and Engineered Sex Ratio Distortion in Insects
23010A. Compton and Z. Tu, Frontiers in Ecology and Evolution, 10. 2022-06-15 08:25:52.
Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.
Meiotic behavior, transmission and active genes of B chromosomes in the cichlid Astatotilapia latifasciata: new clues about nature, evolution and maintenance of accessory elements
22951A. L. Cardoso, N. B. Venturelli, I. da Cruz, F. M. de Sá Patroni, D. de Moraes, R. A. de Oliveira, R. Benavente and C. Martins, Molecular Genetics and Genomics, 2022-06-15 06:37:12.
Supernumerary B chromosomes (Bs) are dispensable genetic elements widespread in eukaryotes and are poorly understood mainly in relation to mechanisms of maintenance and transmission. The cichlid Astatotilapia latifasciata can harbor Bs in a range of 0 (named B -) and 1-2 (named B +). The B in A. latifasciata is rich in several classes of repetitive DNA sequences, contains protein coding genes, and affects hosts in diverse ways, including sex-biased effects. To advance in the knowledge about the mechanisms of maintenance and transmission of B chromosomes in A. latifasciata, here, we studied the meiotic behavior in males and transmission rates of A. latifasciata B chromosome. We also analyzed structurally and functionally the predicted B chromosome copies of the cell cycle genes separin-like, tubb1-like and kif11-like. We identified in the meiotic structure relative to the B chromosome the presence of proteins associated with Synaptonemal Complex organization (SMC3, SYCP1 and SYCP3) and found that the B performs self-pairing. These data suggest that isochromosome formation was a step during B chromosome evolution and this element is in a stage of diversification of the two arms keeping the self-pairing behavior to protect the A chromosome complement of negative effects of recombination. Moreover, we observed no occurrence of B-drive and confirmed the presence of cell cycle genes copies in the B chromosome and their transcription in encephalon, muscle and gonads, which can indicates beneficial effects to hosts and contribute to B maintenance.
Generation of Gene Drive Mice for Invasive Pest Population Suppression
22890M. D. Bunting, C. Pfitzner, L. Gierus, M. White, S. Piltz and P. Q. Thomas, Applications of Genome Modulation and Editing, 2022-06-14 06:00:54.
Gene drives are genetic elements that are transmitted to greater than 50% of offspring and have potential for population modification or suppression. While gene drives are known to occur naturally, the recent emergence of CRISPR-Cas9 genome-editing technology has enabled generation of synthetic gene drives in a range of organisms including mosquitos, flies, and yeast. For example, studies in Anopheles mosquitos have demonstrated >95% transmission of CRISPR-engineered gene drive constructs, providing a possible strategy for malaria control. Recently published studies have also indicated that it may be possible to develop gene drive technology in invasive rodents such as mice. Here, we discuss the prospects for gene drive development in mice, including synthetic “homing drive” and X-shredder strategies as well as modifications of the naturally occurring t haplotype. We also provide detailed protocols for generation of gene drive mice through incorporation of plasmid-based transgenes in a targeted and non-targeted manner. Importantly, these protocols can be used for generating transgenic mice for any project that requires insertion of kilobase-scale transgenes such as knock-in of fluorescent reporters, gene swaps, overexpression/ectopic expression studies, and conditional “floxed” alleles.
Selective targeting of biting females to control mosquito-borne infectious diseases
22953B. B. Kojin, A. Compton, Z. N. Adelman and Z. Tu, Trends in Parasitology, 2022-06-13 06:48:00.
Mosquitoes are vectors for a number of infectious diseases. Only females feed on blood to provision for their embryos and, in doing so, transmit pathogens to the associated vertebrate hosts. Therefore, sex is an important phenotype in the context of genetic control programs, both for sex separation in the rearing facilities to avoid releasing biting females and for ways to distort the sex ratio towards nonbiting males. We review recent progress in the fundamental knowledge of sex determination and sex chromosomes in mosquitoes and discuss new methods to achieve sex separation and sex ratio distortion to help control mosquito-borne infectious diseases. We conclude by suggesting a few critical areas for future research.
Iterative evolution of supergene-based social polymorphism in ants
22899T. Kay, Q. Helleu and L. Keller, Philos Trans R Soc Lond B Biol Sci, 377:20210196. 2022-06-13 06:17:44.
Species commonly exhibit alternative morphs, with individual fate being determined during development by either genetic factors, environmental cues or a combination thereof. Ants offer an interesting case study because many species are polymorphic in their social structure. Some colonies contain one queen while others contain many queens. This variation in queen number is generally associated with a suite of phenotypic and life-history traits, including mode of colony founding, queen lifespan, queen-worker dimorphism and colony size. The basis of this social polymorphism has been studied in five ant lineages, and remarkably social morph seems to be determined by a supergene in all cases. These 'social supergenes' tend to be large, having formed through serial inversions, and to comprise hundreds of linked genes. They have persisted over long evolutionary timescales, in multiple lineages following speciation events, and have spread between closely related species via introgression. Their evolutionary dynamics are unusually complex, combining recessive lethality, spatially variable selection, selfish genetic elements and non-random mating. Here, we synthesize the five cases of supergene-based social polymorphism in ants, highlighting interesting commonalities, idiosyncrasies and implications for the evolution of polymorphisms in general. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Unbalanced selection: the challenge of maintaining a social polymorphism when a supergene is selfish
22895A. G. Tafreshi, S. P. Otto and M. Chapuisat, Philos Trans R Soc Lond B Biol Sci, 377:20210197. 2022-06-13 06:11:36.
Supergenes often have multiple phenotypic effects, including unexpected detrimental ones, because recombination suppression maintains associations among co-adapted alleles but also allows the accumulation of recessive deleterious mutations and selfish genetic elements. Yet, supergenes often persist over long evolutionary periods. How are such polymorphisms maintained in the face of selection, drive and drift? We present a population genetic model that investigates the conditions necessary for a stable polymorphic equilibrium when one of the supergene haplotypes is a selfish genetic element. The model fits the characteristics of the Alpine silver ant, Formica selysi, in which a large supergene underlies colony social organization, and one haplotype distorts Mendelian transmission by killing progeny that did not inherit it. The model shows that such maternal-effect killing strongly limits the maintenance of social polymorphism. Under random mating, transmission ratio distortion prevents rare single-queen colonies from invading populations of multiple-queen colonies, regardless of the fitness of each genotype. A stable polymorphic equilibrium can, however, be reached when high rates of assortative mating are combined with large fitness differences among supergene genotypes. The model reveals that the persistence of the social polymorphism is non-trivial and expected to occur only under restrictive conditions that deserve further empirical investigation. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Supergene potential of a selfish centromere
22893F. Finseth, K. Brown, A. Demaree and L. Fishman, Philos Trans R Soc Lond B Biol Sci, 377:20210208. 2022-06-13 06:07:46.
Selfishly evolving centromeres bias their transmission by exploiting the asymmetry of female meiosis and preferentially segregating to the egg. Such female meiotic drive systems have the potential to be supergenes, with multiple linked loci contributing to drive costs or enhancement. Here, we explore the supergene potential of a selfish centromere (D) in Mimulus guttatus, which was discovered in the Iron Mountain (IM) Oregon population. In the nearby Cone Peak population, D is still a large, non-recombining and costly haplotype that recently swept, but shorter haplotypes and mutational variation suggest a distinct population history. We detected D in five additional populations spanning more than 200 km; together, these findings suggest that selfish centromere dynamics are widespread in M. guttatus. Transcriptome comparisons reveal elevated differences in expression between driving and non-driving haplotypes within, but not outside, the drive region, suggesting large-scale cis effects of D's spread on gene expression. We use the expression data to refine linked candidates that may interact with drive, including Nuclear Autoantigenic Sperm Protein (NASP(SIM3)), which chaperones the centromere-defining histone CenH3 known to modify Mimulus drive. Together, our results show that selfishly evolving centromeres may exhibit supergene behaviour and lay the foundation for future genetic dissection of drive and its costs. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Mendel’s First Law: partisan interests and the parliament of genes
23006C. Veller, Heredity, 2022-06-11 07:51:41.
Mendel’s First Law requires explanation because of the possibility of ‘meiotic drivers’, genes that distort fair segregation for selfish gain. The suppression of drive, and the restoration of fair segregation, is often attributed to genes at loci unlinked to the drive locus—such genes cannot benefit from drive but do suffer its associated fitness costs. However, selection can also favour suppressors at loci linked to the drive locus, raising the question of whether suppression of drive usually comes from linked or unlinked loci. Here, I study linked and unlinked suppression in a two-locus model with initial stable polymorphism at the drive locus. I find that the invasion rate of suppressors is a decreasing function of the recombination fraction between the drive and suppressor loci. Surprisingly, the relative likelihood of unlinked vs. linked suppression increases with the strength of drive and is insensitive to the fitness costs of the driver allele. I find that the chromosomal position of the driver influences how rapidly it is suppressed, with a driver in the middle of a chromosome suppressed more rapidly than a driver near the tip. When drive is strong, only a small number of chromosomes are required for suppression usually to derive from unlinked loci. In contrast, when drive is weak, and especially when suppressor alleles are associated with fitness costs, suppression will usually come from linked loci unless the genome comprises many chromosomes.
Non-Mendelian segregation and transmission drive of B chromosomes
22725J. P. M. Camacho, Chromosome Research, 2022-06-03 07:58:27.
Selfish genetic elements (SGE) get a transmission advantage (drive) thanks to their non-Mendelian inheritance. Here I identify eight steps during the reproductive cycle that can be subverted by SGEs to thrive in natural populations. Even though only three steps occur during meiosis, most cases of segregation distortion are considered “meiotic drive sensu lato.” As this is a source of unnecessary contradictions, I suggest always using the term “transmission ratio distortion” (TRD). Chromosomal SGEs (e.g., B chromosomes) exhibit almost all types of TRD. In plants, the best-studied type of TRD for B chromosomes occurs post-meiotically during male gametophyte maturation. However, in animals, the two main types are pre-meiotic and meiotic TRDs, in all cases associated with gonotaxis (i.e., a preference of B chromosomes for germ cells). Frequently, TRD drivers in genic SGEs (e.g., t-alleles and segregation distorters in Drosophila) are paralogous copies of genes from the standard genome, whereas their targets can be other genes or satellite DNA (satDNA). As B chromosomes are often rich in satDNA and contain paralogous copies of A chromosome genes, perhaps their drive mechanisms are similar to those of genic SGEs. So far, the only association between a B chromosome gene and TRD is the gene haplodizer in Nasonia vitripennis. The discovery of B-genes controlling B-drive in other species does not appear to be far off, but experimental crosses will be needed to simultaneously test the TRD of a given B chromosome and the expression of its genes.
A meiotic driver alters sperm form and function in house mice: a possible example of spite
22697L. Winkler and A. K. Lindholm, Chromosome Research, 2022-06-01 14:48:38.
The ability to subvert independent assortment of chromosomes is found in many meiotic drivers, such as the t haplotype in house mice Mus musculus, in which the t-bearing chromosomal homolog is preferentially transmitted to offspring. This is explained by a poison-antidote system, in which developing + and t sperm in testes of + /t males are exposed to 'poison' coded by t loci, from which t sperm are protected, allowing t sperm an overwhelming fertilisation advantage in monogamous matings. This system is thought to result in poorly and normally motile sperm subpopulations within + /t sperm, leaving t sperm unharmed. Conversely, we found that the fastest quartile of sperm from + /t males swam more slowly, both forwards and along their travel path, and had reduced straightness and linearity, compared to the fastest quartile of + / + sperm. Moreover, sperm from + /t males had shorter tails and narrower heads than + / + sperm, and these morphological differences covaried with motility differences. Finally, + /t traits did not show evidence of bimodal distributions. We conclude that the t haplotype drive results in lasting damage to the motility of both + and t developing sperm, although previous studies indicate that + must be more harmed than t sperm. This damage to all sperm may explain the low success of + /t males in sperm competition with + / + males, seen in earlier studies. We propose that the harm the t causes to itself could be termed 'spiteful', which may also be common to other gamete-harming meiotic drive systems.
The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility
22570R. Kaur, B. A. Leigh, I. T. Ritchie and S. R. Bordenstein, PLOS Biology, 20:e3001584. 2022-05-24 08:55:13.
In Drosophila melanogaster, germline expression of the Wolbachia proteins CifA and CifB causes cytoplasmic incompatibility, but how this impairs male reproduction remains unclear. This study shows how Cif proteins encoded by the endosymbiont prophage invade the fly’s gametic nuclei and modify the histone-protamine transition of spermatogenesis.
The fate of a suppressed X-linked meiotic driver: experimental evolution in Drosophila simulans
22676H. Bastide, D. Ogereau, C. Montchamp-Moreau and P. R. Gérard, Chromosome Research, 2022-04-30 07:53:46.
Sex-ratio (SR) meiotic drivers are X-linked selfish genetic elements that promote their own transmission by preventing the production of Y-bearing sperm, which usually lowers male fertility. The spread of SR drivers in populations is expected to trigger the evolution of unlinked drive suppressors, a theoretically predicted co-evolution that has been observed in nature. Once completely suppressed, the drivers are expected either to decline if they still affect the fitness of their carriers, or to evolve randomly and possibly get fixed if the suppressors eliminate their deleterious effects. To explore this issue, we used the Paris sex-ratio system of Drosophila simulans in which drive results from the joint effect of two elements on the X chromosome: a segmental duplication and a deficient allele of the HP1D2 gene. We set up six experimental populations starting with 2/3 of X chromosomes carrying both elements (X(SR)) in a fully suppressing background. We let them evolve independently during almost a hundred generations under strong sexual competition, a condition known to cause the rapid disappearance of unsuppressed Paris X(SR) in previous experimental populations. In our study, the fate of X(SR) chromosomes varied among populations, from extinction to their maintenance at a frequency close to the starting one. While the reasons for these variable outcomes are still to be explored, our results show that complete suppression can prevent the demise of an otherwise deleterious X(SR) chromosome, turning a genetic conflict into cooperation between unlinked loci. Observations in natural populations suggest a contrasting fate of the two elements: disappearance of the duplication and maintenance of deficient HP1D2 alleles.
Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load
22103B. Navarro-Dominguez, C.-H. Chang, C. L. Brand, C. A. Muirhead, D. C. Presgraves and A. M. Larracuente, eLife, 11:e78981. 2022-04-29 09:52:33.
In this work, we investigate the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world, and have implications for supergene evolution broadly.
The evolutionary significance of meiotic drive
21913J. B. Searle and F. P.-M. de Villena, Heredity, 2022-04-25 08:34:39.
In this essay, we will focus on‘true meiotic drive’ where the distorted transmission does arise within meiosis itself (Zanders and Unckless2019),specifically in females. Here, the non-transmission of one of the products of meiotic division is inherent in the gametogenic process—with the formation of a polar body as the functionless by-product of division, with the egg continuing on as the viable entity. The meiotic drive is therefore the biased segregation in favour of one type of allele such that it is most commonly retained in the egg at the cost of the other type of allele, which most commonly ends up in the polar body. The biased segregation can occur at either the first or second division ofmeiosis—both of which generate a functionless polar body, suchthat there is ultimately only one viable product of the two divisions—the final version of the egg, which then becomes a zygote on fertilisation.
Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders
22219V. Jonsson, H. Awan, N. D. Jones, T. B. Johannesen, K. Thogersen, B. A. Steig, G. Andorsdottir and G. E. Tjonnfjord, Scientific Reports, 12:6138. 2022-04-12 15:37:58.
The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, <
Explainer: The Gene Drive Technology
21701P. Shah, CRISPR Medicine News, 2022-04-11 08:45:54.
Gene drives are genetic elements that can quickly spread through populations and have nearly a 100% chance of passing the genes they carry to the next generation. Synthetic gene drive is a technology of genetic engineering through which certain desired traits can be introduced to almost all individuals in a population. Researchers can either eliminate a species or alter the genetic makeup of living organisms through gene drive technology.
Evolution of eukaryotic centromeres by drive and suppression of selfish genetic elements
21559T. Kumon and M. A. Lampson, Seminars in Cell and Developmental Biology, 2022-03-25 12:12:40.
Despite the universal requirement for faithful chromosome segregation, eukaryotic centromeres are rapidly evolving. It is hypothesized that rapid centromere evolution represents an evolutionary arms race between selfish genetic elements that drive, or propagate at the expense of organismal fitness, and mechanisms that suppress fitness costs. Selfish centromere DNA achieves preferential inheritance in female meiosis by recruiting more effector proteins that alter spindle microtubule interaction dynamics. Parallel pathways for effector recruitment are adaptively evolved to suppress functional differences between centromeres. Opportunities to drive are not limited to female meiosis, and selfish transposons, plasmids and B chromosomes also benefit by maximizing their inheritance. Rapid evolution of selfish genetic elements can diversify suppressor mechanisms in different species that may cause hybrid incompatibility.
GeneConvene Global Collaborative Webinar Series | Genetic Drive Systems in Nature
20552David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2022-03-09 14:02:21.
Intra genomic genetic conflicts are ubiquitous in nature and have shaped and continue to shape the evolution of plants, animals, and microbes. These conflicts can result in preferential transmission - drive - of genes, various genetic elements, and even whole chromosomes. Interest in drive systems extends beyond the basic sciences to technologists who are exploring natural and synthetic drives as agents to suppress or modify species in nature. This webinar series will explore the variety of drive systems found in nature, mechanisms responsible for drive and impacts of drive on behavior and evolution..
Selfish migrants: How a meiotic driver is selected to increase dispersal
20575J. N. Runge, H. Kokko and A. K. Lindholm, J Evol Biol, 2022-03-07 10:54:44.
Meiotic drivers are selfish genetic elements that manipulate meiosis to increase their transmission to the next generation to the detriment of the rest of the genome. One example is the t haplotype in house mice, which is a naturally occurring meiotic driver with deleterious traits-poor fitness in polyandrous matings and homozygote inviability or infertility-that prevent its fixation. Recently, we discovered and validated a novel effect of t in a long-term field study on free-living wild house mice and with experiments: t-carriers are more likely to disperse. Here, we ask what known traits of the t haplotype can select for a difference in dispersal between t-carriers and wildtype mice. To that end, we built individual-based models with dispersal loci on the t and the homologous wildtype chromosomes. We also allow for density-dependent expression of these loci. The t haplotype consistently evolves to increase the dispersal propensity of its carriers, particularly at high densities. By examining variants of the model that modify different costs caused by t, we show that the increase in dispersal is driven by the deleterious traits of t, disadvantage in polyandrous matings and lethal homozygosity or male sterility. Finally, we show that an increase in driver-carrier dispersal can evolve across a range of values in driver strength and disadvantages.
A-to-I mRNA editing controls spore death induced by a fungal meiotic drive gene in homologous and heterologous expression systems
20415J. M. Lohmar, N. A. Rhoades, T. N. Patel, R. H. Proctor, T. M. Hammond and D. W. Brown, Genetics, 2022-02-16 16:59:28.
Spore killers are meiotic drive elements that can block development of sexual spores in fungi. In the maize ear rot and mycotoxin-producing fungus Fusarium verticillioides, a spore killer called SkK has been mapped to a 102-kb interval of chromosome V. Here, we show that a gene within this interval, SKC1, is required for SkK-mediated spore killing and meiotic drive. We also demonstrate that SKC1 is associated with at least four transcripts, two sense (sense-SKC1a and sense-SKC1b) and two antisense (antisense-SKC1a and antisense-SKC1b). Both antisense SKC1 transcripts lack obvious protein-coding sequences and thus appear to be non-coding RNAs. In contrast, sense-SKC1a is a protein-coding transcript that undergoes A-to-I editing to sense-SKC1b in sexual tissue. Translation of sense-SKC1a produces a 70 amino acid protein (Skc1a), whereas translation of sense-SKC1b produces an 84 amino acid protein (Skc1b). Heterologous expression analysis of SKC1 transcripts shows that sense-SKC1a also undergoes A-to-I editing to sense-SKC1b during the Neurospora crassa sexual cycle. Site directed mutagenesis studies indicate that Skc1b is responsible for spore killing in F. verticillioides and that it induces most meiotic cells to die in N. crassa. Finally, we report that SKC1 homologs are present in over 20 Fusarium species. Overall, our results demonstrate that fungal meiotic drive elements like SKC1 can influence the outcome of meiosis by hijacking a cell's A-to-I editing machinery and that the involvement of A-to-I editing in a fungal meiotic drive system does not preclude its horizontal transfer to a distantly related species.
Hoisted with his own petard: how sex-ratio meiotic drive in Drosophila affnis creates resistance alleles that limit its spread
20440W.-J. Ma, K. B. Patch, E. M. Knoles, M. M. Shoaib and R. L. Unckless, bioRxiv, 2022.02.14.480432. 2022-02-16 09:24:56.
Meiotic drivers are selfish genetic elements that tinker with gameto-genesis to bias their own transmission into the next generation of off-spring. Such tinkering can have significant consequences on gameto-genesis and end up hampering the spread of the driver. In Drosophila affrnis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are more than 95% female. Interestingly, D. affrnis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 50X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.Competing Interest StatementThe authors have declared no competing interest.
The spore killers, fungal meiotic driver elements
20390A. A. Vogan, I. Martinossi-Allibert, S. L. Ament-Velásquez, J. Svedberg and H. Johannesson, Mycologia, 2022-02-09 09:22:39.
During meiosis, both alleles of any given gene should have equal chances of being inherited by the progeny. There are a number of reasons why, however, this is not the case, with one of the most intriguing instances presenting itself as the phenomenon of meiotic drive. Genes that are capable of driving can manipulate the ratio of alleles among viable meiotic products so that they are inherited in more than half of them. In many cases, this effect is achieved by direct antagonistic interactions, where the driving allele inhibits or otherwise eliminates the alternative allele. In ascomycete fungi, meiotic products are packaged directly into ascospores; thus, the effect of meiotic drive has been given the nefarious moniker, "spore killing." In recent years, many of the known spore killers have been elevated from mysterious phenotypes to well-described systems at genetic, genomic, and molecular levels. In this review, we describe the known diversity of spore killers and synthesize the varied pieces of data from each system into broader trends regarding genome architecture, mechanisms of resistance, the role of transposable elements, their effect on population dynamics, speciation and gene flow, and finally how they may be developed as synthetic drivers. We propose that spore killing is common, but that it is under-observed because of a lack of studies on natural populations. We encourage researchers to seek new spore killers to build on the knowledge that these remarkable genetic elements can teach us about meiotic drive, genomic conflict, and evolution more broadly.
chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche
19728C. Y. Tseng, M. Burel, M. Cammer, S. Harsh, M. S. Flaherty, S. Baumgartner and E. A. Bach, Developmental Cell, 2021-12-22 12:51:45.
Niches maintain a finite pool of stem cells via restricted space and short-range signals. Stem cells compete for limited niche resources, but the mechanisms regulating competition are poorly understood. Using the Drosophila testis model, we show that germline stem cells (GSCs) lacking the transcription factor Chinmo gain a competitive advantage for niche access. Surprisingly, chinmo(-/-) GSCs rely on a new mechanism of competition in which they secrete the extracellular matrix protein Perlecan to selectively evict non-mutant GSCs and then upregulate Perlecan-binding proteins to remain in the altered niche. Over time, the GSC pool can be entirely replaced with chinmo(-/-) cells. As a consequence, the mutant chinmo allele acts as a gene drive element; the majority of offspring inherit the allele despite the heterozygous genotype of the parent. Our results suggest that the influence of GSC competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.
Diverse mating phenotypes impact the spread of wtf meiotic drivers in Schizosaccharomyces pombe
20396J. F. L. Hernandez, R. M. Helston, J. J. Lange, R. B. Billmyre, S. H. Schaffner, M. T. Eickbush, S. McCroskey and S. E. Zanders, Elife, 10:30. 2021-12-13 09:37:02.
Meiotic drivers are genetic elements that break Mendel's law of segregation to be transmitted into more than half of the offspring produced by a heterozygote. The success of a driver relies on outcrossing (mating between individuals from distinct lineages) because drivers gain their advantage in heterozygotes. It is, therefore, curious that Schizosaccharomyces pombe, a species reported to rarely outcross, harbors many meiotic drivers. To address this paradox, we measured mating phenotypes in S. pombe natural isolates. We found that the propensity for cells from distinct clonal lineages to mate varies between natural isolates and can be affected both by cell density and by the available sexual partners. Additionally, we found that the observed levels of preferential mating between cells from the same clonal lineage can slow, but not prevent, the spread of a wtf meiotic driver in the absence of additional fitness costs linked to the driver. These analyses reveal parameters critical to understanding the evolution of S. pombe and help explain the success of meiotic drivers in this species. eLife digest The fission yeast, Schizosaccharomyces pombe, is a haploid organism, meaning it has a single copy of each of its genes. S. pombe cells generally carry one copy of each chromosome and can reproduce clonally by duplicating these chromosomes and then dividing into two cells. However, when the yeast are starving, they can reproduce sexually. This involves two cells mating by fusing together to create a 'diploid zygote', which contains two copies of each gene. The zygote then undergoes 'meiosis', a special type of cell division in which the zygote first duplicates its genome and then divides twice. This results in four haploid spores which are analogous to sperm and eggs in humans that each contain one copy of the genome. The spores will grow and divide normally when conditions improve. The genes carried by each of the haploid spores depend on the cells that formed the zygote. If the two 'parent' yeast had the same version or 'allele' of a gene, all four spores will have it in their genome. However, if the two parents have different alleles, only 50% of the offspring will carry each version. Although this is usually the case, there are certain alleles, called meiotic drivers, that are transmitted to all offspring even in situations where it is only carried by one parent. Meiotic drivers can be found in many organisms, including mammals, but their behavior is easiest to study in yeast. Meiotic drivers known as killers achieve this by disposing of any 'sister' spores that do not inherit the same allele of this gene. This 'killing' can only happen when only one of the 'parents' carries the driver. This scenario is thought to rarely occur in species that inbreed, as inbreeding leads to both gene copies being the same. However, this does not appear to be the case for S. pombe, which contain a whole family of killer meiotic drivers, the wtf genes, despite also being reported to mainly inbreed. To investigate this contradiction, Lopez Hernandez et al. isolated several genetically distinct populations of S.pombe. These isolates were grown together to determine how often the each one would outcross (mate with an individual from a different population) or inbreed. The results found that levels of inbreeding varied between isolates. Next, Lopez Hernandez et al. used mathematical modelling and experimental evolution analyses to study how wtf drivers spread amongst these populations. This revealed that wtf genes spread faster in populations with more outcrossing. In some instances, the wtf driver was linked to a gene that could harm the population. In these cases, Lopez Hernandez et al. found than inbreeding could purge these drivers and stop them from spreading the dangerous alleles through the population. Lopez Hernandez et al. establish a simple experimental system to model driver evolution and experimentally demonstrate how key parameters, such as outcrossing rates, affect the spread of these genes. Understanding how meiotic drivers spread is important, as these systems could potentially be used to modify populations important to humans, such as crops or disease vectors.
Nuclear transport genes recurrently duplicate by means of RNA intermediates in Drosophila but not in other insects
19591A. Mirsalehi, D. N. Markova, M. Eslamieh and E. Betrán, BMC Genomics, 22:876. 2021-12-06 17:52:07.
We find that most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. We also retrieve many pseudogenes for the Ran gene. Some of the duplicates are relatively young and likely contributing to the turnover expected for genes under strong but changing selective pressures. These duplications are potentially revealing what features of nuclear transport are under selection. Unlike in flies, we find only a few duplications when we study the Drosophila duplicated nuclear transport genes in dipteran species outside of Drosophila, and none in other insects.
A flurry of sex-ratio distorters
19527A. A. Vogan, Nature Ecology and Evolution, 2021-12-03 19:49:56.
Two analyses of long-read sequencing show that the Winters sex-ratio distorter of Drosophila has been a part of a recent gene family expansion, coupled to the appearance of suppressors, in a genomic arms race driven by satellite DNA.
Rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors
19515J. Vedanayagam, C. J. Lin and E. C. Lai, Nature Ecology and Evolution, 2021-12-03 17:20:42.
Meiotic drivers are a class of selfish genetic elements whose existence is frequently hidden due to concomitant suppressor systems. Accordingly, we know little of their evolutionary breadth and molecular mechanisms. Here, we trace the evolution of the Dox meiotic drive system in Drosophila simulans, which affects male-female balance (sex ratio). Dox emerged via stepwise mobilization and acquisition of multiple D. melanogaster gene segments including from protamine, which mediates compaction of sperm chromatin. Moreover, we reveal novel Dox homologs and massive amplification of Dox superfamily genes on X chromosomes of its closest sisters D. mauritiana and D. sechellia. Emergence of Dox loci is tightly associated with 359-class satellite repeats that flank de novo genomic copies. In concert, we find coordinated diversification of autosomal hairpin RNA-class siRNA loci that target subsets of Dox superfamily genes. Overall, we reveal fierce genetic arms races between meiotic drive factors and siRNA suppressors associated with recent speciation.
Synthetic sex ratio distorters based on CRISPR for the control of harmful insect populations
19369Fasulo, B., Meccariello, A., Papathanos, P. A., and Windbichler, N., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 16:55:38.
Since the overall reproductive output of a population is typically determined by the fertility of its females, which are rate-limiting in gamete production, a successful way to genetically control a population should involve artificially biasing the sex ratio towards males. In male heterogametic species, this could be achieved by the expression of a transgene-encoded endonuclease during spermatogenesis that would target and "shred" the X chromosome at several loci. This would prevent the transmission of X chromosome bearing gametes to the progeny, generating only males. Recent developments in molecular and synthetic biology have provided genome editing tools with great potential to engineer the genome of different species. Given the targeting flexibility of CRISPR-based endonucleases, it may now be possible to test whether X chromosome shredding has the potential to become a universal strategy to genetically control a wide variety of insect pests, of both agricultural and public health relevance.
Tubulin post-translational modifications in meiosis
19433T. Akera, Seminars in Cell & Developmental Biology, 2021-11-23 20:29:32.
Haploid gametes are produced from diploid parents through meiosis, a process inherent to all sexually reproducing eukaryotes. Faithful chromosome segregation in meiosis is essential for reproductive success, although it is less clear how the meiotic spindle achieves this compared to the mitotic spindle. It is becoming increasingly clear that tubulin post-translational modifications (PTMs) play critical roles in regulating microtubule functions in many biological processes, and meiosis is no exception. Here, I review recent advances in the understanding of tubulin PTMs in meiotic spindles, especially focusing on their roles in spindle integrity, oocyte aging, and non-Mendelian transmission.
Transmission distortion and genetic incompatibilities between alleles in a multigenerational mouse advanced intercross line
19320D. Arends, S. Kärst, S. Heise, P. Korkuc, D. Hesse and G. A. Brockmann, Genetics, 2021-11-15 14:07:56.
While direct additive and dominance effects on complex traits have been mapped repeatedly, additional genetic factors contributing to the heterogeneity of complex traits have been scarcely investigated. To assess genetic background effects, we investigated transmission ratio distortions (TRDs) of alleles from parent to offspring using an advanced intercross line (AIL) of an initial cross between the mouse inbred strains C57BL/6NCrl (B6N) and BFMI860-12 (BFMI). 341 males of generation 28 and their respective 61 parents and 66 grandparents were genotyped using Mega Mouse Universal Genotyping Arrays (MegaMUGA). TRDs were investigated using allele transmission asymmetry tests, and pathway overrepresentation analysis was performed. Sequencing data was used to test for overrepresentation of non-synonymous SNPs in TRD regions. Genetic incompatibilities were tested using the Bateson-Dobzhansky-Muller two-locus model. 62 TRD regions were detected, many in close proximity to the telocentric centromere. TRD regions contained 44.5% more non-synonymous SNPs than randomly selected regions (182 vs. 125.9 ± 17.0, P < 1x10-4). Testing for genetic incompatibilities between TRD regions identified 29 genome-wide significant incompatibilities between TRD regions (P(BF) < 0.05). Pathway overrepresentation analysis of genes in TRD regions showed that DNA methylation, epigenetic regulation of RNA, and meiotic/meiosis regulation pathways were affected independent of the parental origin of the TRD. Paternal BFMI TRD regions showed overrepresentation in the small interfering RNA (siRNA) biogenesis and in the metabolism of lipids and lipoproteins. Maternal B6N TRD regions harbored genes involved in meiotic recombination, cell death, and apoptosis pathways. The analysis of genes in TRD regions suggests the potential distortion of protein-protein interactions influencing obesity and diabetic retinopathy as a result of disadvantageous combinations of allelic variants in Aass, Pgx6 and Nme8. Using an AIL significantly improves the resolution at which we can investigate TRD. Our analysis implicates distortion of protein-protein interactions as well as meiotic drive as the underlying mechanisms leading to the observed TRD in our AIL. Furthermore, genes with large amounts of non-synonymous SNPs located in TRD regions are more likely to be involved in pathways that are related to the phenotypic differences between the parental strains. Genes in these TRD regions provide new targets for investigating genetic adaptation, protein-protein interactions, and determinants of complex traits such as obesity.
Centromere function in asymmetric cell division in Drosophila female and male germline stem cells
19322A. M. Kochendoerfer, F. Modafferi and E. M. Dunleavy, Open Biology, 11:210107. 2021-11-03 14:14:53.
The centromere is the constricted chromosomal region required for the correct separation of the genetic material at cell division. The kinetochore protein complex assembles at the centromere and captures microtubules emanating from the centrosome to orchestrate chromosome segregation in mitosis and meiosis. Asymmetric cell division (ACD) is a special type of mitosis that generates two daughter cells with different fates. Epigenetic mechanisms operating at the centromere have been proposed to contribute to ACD. Recent studies have shown that an asymmetric distribution of CENP-A—the centromere-specific histone H3 variant—between sister chromatids can bias chromosome segregation in ACD. In stem cells, this leads to non-random sister chromatid segregation, which can affect cell fate. These findings support the ‘silent sister' hypothesis, according to which the mechanisms of ACD are epigenetically regulated through centromeres. Here, we review the recent data implicating centromeres in ACDs and cell fate in Drosophila melanogaster female and male germline stem cells.
A Maternal-Effect Toxin Affects Epithelial Differentiation and Tissue Mechanics in Caenorhabditis elegans
19128C. Lehmann and C. Pohl, Frontiers in Cell and Developmental Biology, 9. 2021-10-14 14:25:20.
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These elements seem to act as modification-rescue systems, also called toxin/antidote pairs. Here we show that the maternal-effect toxin/zygotic antidote pair sup-35/pha-1 is required for proper expression of apical junction (AJ) components in epithelia and that sup-35 toxicity increases when pathways that establish and maintain basal epithelial characteristics, die-1, elt-1, lin-26, and vab-10, are compromised. We demonstrate that pha-1(e2123) embryos, which lack the antidote, are defective in epidermal morphogenesis and frequently fail to elongate. Moreover, seam cells are frequently misshaped and mispositioned and cell bond tension is reduced in pha-1(e2123) embryos, suggesting altered tissue material properties in the epidermis. Several aspects of this phenotype can also be induced in wild-type embryos by exerting mechanical stress through uniaxial loading. Seam cell shape, tissue mechanics, and elongation can be restored in pha-1(e2123) embryos if expression of the AJ molecule DLG-1/Discs large is reduced. Thus, our experiments suggest that maternal-effect toxicity disrupts proper development of the epidermis which involves distinct transcriptional regulators and AJ components.
Sexual selection can partly explain low frequencies of Segregation Distorter alleles
18815T. A. Keaney, T. M. Jones and L. Holman, Proceedings of the Royal Society B: Biological Sciences, 288:20211190. 2021-09-29 15:21:33.
The Segregation Distorter (SD) allele found in Drosophila melanogaster distorts Mendelian inheritance in heterozygous males by causing developmental failure of non-SD spermatids, such that greater than 90% of the surviving sperm carry SD. This within-individual advantage should cause SD to fix, and yet SD is typically rare in wild populations. Here, we explore whether this paradox can be resolved by sexual selection, by testing if males carrying three different variants of SD suffer reduced pre- or post-copulatory reproductive success. We find that males carrying the SD allele are just as successful at securing matings as control males, but that one SD variant (SD-5) reduces sperm competitive ability and increases the likelihood of female remating. We then used these results to inform a theoretical model; we found that sexual selection could limit SD to natural frequencies when sperm competitive ability and female remating rate equalled the values observed for SD-5. However, sexual selection was unable to explain natural frequencies of the SD allele when the model was parameterized with the values found for two other SD variants, indicating that sexual selection alone is unlikely to explain the rarity of SD.
Evolutionary robustness of killer meiotic drives
18676P. G. Madgwick and J. B. Wolf, Evolution Letters, 2021-09-12 12:53:08.
A meiotic driver is a selfish genetic element that interferes with the process of meiosis to promote its own transmission. The most common mechanism of interference is gamete killing, where the meiotic driver kills gametes that do not contain it. A killer meiotic driver is predicted to spread rapidly through a population at the expense of other genes in the rest of the genome. The rapid spread of a killer meiotic driver is expected to be chased by the rapid spread of a suppressor that returns fair meiosis. Paradoxically, while this might imply that meiotic drivers should be evolutionarily transient, numerous ancient killer meiotic drivers have been discovered that have persisted for millions of years. To understand the rationale that could potentially explain such evolutionary robustness, we explore different possible mechanisms of killer meiotic drive and the different possible associated mechanisms of suppression. We use a framework that considers how the different stages of meiosis result in different structured interactions among cells with different genotypes in various combinations. Across possible interactions, we show that there are three genotypically distinct drive mechanisms that create alternative selective conditions for the spread of different types of suppressors. We show that killer meiotic drivers are more evolutionarily robust if they operate among sister cells (after meiosis I and before meiosis II) than at any other point during meiosis. The different drive mechanisms we identify make testable predictions that could explain why some killer meiotic drivers are transient while others are ancient.
Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila
18354C. A. Muirhead and D. C. Presgraves, Nature Ecology & Evolution, 2021-09-06 14:01:24.
Sex chromosomes are susceptible to the evolution of selfish meiotic drive elements that bias transmission and distort progeny sex ratios. Conflict between such sex-ratio drivers and the rest of the genome can trigger evolutionary arms races resulting in genetically suppressed ‘cryptic’ drive systems. The Winters cryptic sex-ratio drive system of Drosophila simulans comprises a driver, Distorter on the X (Dox) and an autosomal suppressor, Not much yang, a retroduplicate of Dox that suppresses via production of endogenous small interfering RNAs (esiRNAs). Here we report that over 22 Dox-like (Dxl) sequences originated, amplified and diversified over the ~250,000-year history of the three closely related species, D. simulans, D. mauritiana and D. sechellia. The Dxl sequences encode a rapidly evolving family of protamines. Dxl copy numbers amplified by ectopic exchange among euchromatic islands of satellite DNAs on the X chromosome and separately spawned four esiRNA-producing suppressors on the autosomes. Our results reveal the genomic consequences of evolutionary arms races and highlight complex interactions among different classes of selfish DNAs.
Unravelling the mystery of female meiotic drive: where we are
18263F. E. Clark and T. Akera, Open Biol, 11:210074. 2021-09-02 13:30:18.
Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.
Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes
18819F. Pajpach, T. Wu, L. Shearwin-Whyatt, K. Jones and F. Grützner, Genes, 12. 2021-08-28 15:33:36.
Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.
Parallel pathways for recruiting effector proteins determine centromere drive and suppression
18266T. Kumon, J. Ma, R. B. Akins, D. Stefanik, C. E. Nordgren, J. Kim, M. T. Levine and M. A. Lampson, Cell, 2021-08-26 13:45:10.
Selfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this "centromere drive." In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting the kinetochore pathway with a divergent allele of CENP-C reduces functional differences between centromeres, whereas disrupting heterochromatin by CENP-B deletion amplifies the differences. Molecular evolution analyses using Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions.
Analysis of the Segregation Distortion of FcRAN1 Genotypes Based on Whole-Genome Resequencing of Fig (Ficus carica L.) Breeding Parents
18171H. Ikegami, K. Shirasawa, H. Yakushiji, S. Yabe, M. Sato, T. Hayashi, K. Tashiro and H. Nogata, Frontiers in Plant Science, 12:8. 2021-08-10 14:56:28.
The common fig (Ficus carica L.) has a gynodioecious breeding system, and its sex phenotype is an important trait for breeding because only female plant fruits are edible. During breeding to select for female plants, we analyzed the FcRAN1 genotype, which is strongly associated with the sex phenotype. In 12 F-1 populations derived from 13 cross combinations, the FcRAN1 genotype segregation ratio was 1:1, whereas the M119226 x H238-107 hybridization resulted in an extremely male-biased segregation ratio (178:7 = male:female). This finding suggests that the segregation distortion was caused by some genetic factor(s). A whole-genome resequencing of breeding parents (paternal and maternal lines) identified 9,061 high-impact SNPs in the parents. A genome-wide linkage analysis exploring the gene(s) responsible for the distortion revealed 194 high-impact SNPs specific to Caprifig6085 (i.e., seed parent ancestor) and 215 high-impact SNPs specific to H238-107 (i.e., pollen parent) in 201 annotated genes. A comparison between the annotated genes and the genes required for normal embryo or gametophyte development and function identified several candidate genes possibly responsible for the segregation distortion. This is the first report describing segregation distortion in F. carica.
Red queen’s race: rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors
17957J. Vedanayagam, C.-J. Lin and E. C. Lai, bioRxiv, 2021.08.05.454923. 2021-08-06 16:51:10.
Meiotic drivers are a class of selfish genetic elements that are widespread across eukaryotes. Their activities are often detrimental to organismal fitness and thus trigger drive suppression to ensure fair segregation during meiosis. Accordingly, their existence is frequently hidden in genomes, and their molecular functions are little known. Here, we trace evolutionary steps that generated the Dox meiotic drive system in Drosophila simulans (Dsim), which distorts male:female balance (sex-ratio) by depleting male progeny. We show that Dox emerged via stepwise mobilization and acquisition of portions of multiple D. melanogaster genes, including the sperm chromatin packaging gene protamine. Moreover, we reveal novel Dox homologs in Dsim and massive, recent, amplification of Dox superfamily genes specifically on X chromosomes of its closest sister species D. mauritiana (Dmau) and D. sechellia (Dsech). The emergence of Dox superfamily genes is tightly associated with 1.688 family satellite repeats that flank de novo genomic copies. In concert, we find coordinated emergence and diversification of autosomal hairpin RNA/siRNAs loci that target subsets of Dox superfamily genes across simulans clade species. Finally, an independent set of protamine amplifications the Y chromosome of D. melanogaster indicates that protamine genes are frequent and recurrent players in sex chromosome dynamics. Overall, we reveal fierce genetic arms races between meiotic drive factors and siRNA suppressors associated with recent speciation.Competing Interest StatementThe authors have declared no competing interest.
Distinct spermiogenic phenotypes underlie sperm elimination in the Segregation Distorter meiotic drive system
17832M. Herbette, X. L. Wei, C. H. Chang, A. M. Larracuente, B. Loppin and R. Dubruille, PLOS Genetics, 17:26. 2021-07-06 13:14:02.
Here we show that SD/SD+ males of different genotypes but with similarly strong degrees of distortion have distinct spermiogenic phenotypes. In some genotypes, SD+ spermatids fail to fully incorporate protamines after the removal of histones, and degenerate during the individualization stage of spermiogenesis. In contrast, in other SD/SD+ genotypes, protamine incorporation appears less disturbed, yet spermatid nuclei are abnormally compacted, and mature sperm nuclei are eventually released in the seminal vesicle. Our analyses of different SD+ chromosomes suggest that the severity of the spermiogenic defects associates with the copy number of the Rsp satellite. We propose that when Rsp copy number is very high (> 2000), spermatid nuclear compaction defects reach a threshold that triggers a checkpoint controlling sperm chromatin quality to eliminate abnormal spermatids during individualization. Author summary In diploid organisms, both alleles of the same gene have an equal chance to be transmitted to the progeny. However, in many species including mammals, insects and plants, selfish genetic elements perturb gametogenesis in a way that favors their own transmission to the detriment of the homologous chromosome that does not carry them. In Drosophila melanogaster, Segregation Distorter (Sd) is a well-characterized selfish locus that induces, by still-unclear mechanisms, the elimination of sperm cells which contain the homologous second chromosome when this carries a large heterochromatic block of repetitive DNA called Rsp. Here, we show that in Sd males, the replacement of histones by sperm specific protamine-like proteins is perturbed in the differentiating Rsp sperm cells, which are then eliminated before their release in the seminal vesicle. However, in some genetic backgrounds, many spermatids Rsp tend to escape this elimination and defective sperm nuclei are found in the seminal vesicle. We show that these phenotypes are partly linked to the number of repeats in the Rsp block and can be modulated by suppressors present in the genetic background. Our work thus helps to understand how selfish loci exploit gametogenesis to favor their own transmission and highlights the essential role of heterochromatin in spermiogenesis progression.
Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population
17511B. A. Haines, F. Barradale and B. L. Dumont, bioRxiv, 2021-06-23 14:26:09.
In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.
First evidence of deviation from Mendelian proportions in a conservation programme
17556C. E. Grueber, K. A. Farquharson, B. R. Wright, G. P. Wallis, C. J. Hogg and K. Belov, Molecular Ecology, 13. 2021-05-29 14:38:25.
Classic Mendelian inheritance is the bedrock of population genetics and underpins pedigree-based management of animal populations. However, assumptions of Mendelian inheritance might not be upheld in conservation breeding programmes if early viability selection occurs, even when efforts are made to equalise genetic contributions of breeders. To test this possibility, we investigated deviations from Mendelian proportions in a captive metapopulation of the endangered Tasmanian devil. This marsupial population is ideal for addressing evolutionary questions in conservation due to its large size, range of enclosure types (varying in environmental conditions), good genomic resources (which aid interpretation), and the species' biology. Devil mothers give birth to more offspring than they can nurse in the pouch, providing the potential for intense viability selection amongst embryos. We used data from 140 known sire-dam-offspring triads to isolate within-family selection from population-level mechanisms (such as mate choice or inbreeding), and compared observed offspring genotypes at 123 targeted SNPs to neutral (i.e., Mendelian) expectations. We found lower offspring heterozygosity than expected, and subtle patterns that varied across a gradient of management intensity from zoo-like enclosures to semi-wild environments for some loci. Meiotic drive or maternal-foetal incompatibilities are consistent with our results, although we cannot statistically confirm these mechanisms. We found some evidence that maternal genotype affects annual litter size, suggesting that family-level patterns are driven by differential offspring mortality before birth or during early development. Our results show that deviations from Mendelian inheritance can occur in conservation programmes, despite best-practice management to prevent selection.
Experiments confirm a dispersive phenotype associated with a natural gene drive system
17036J.-N. Runge and A. K. Lindholm, Royal Society Open Science, 8:202050. 2021-05-12 11:24:14.
Meiotic drivers are genetic entities that increase their own probability of being transmitted to offspring, usually to the detriment of the rest of the organism, thus ‘selfishly’ increasing their fitness. In many meiotic drive systems, driver-carrying males are less successful in sperm competition, which occurs when females mate with multiple males in one oestrus cycle (polyandry). How do drivers respond to this selection? An observational study found that house mice carrying the t haplotype, a meiotic driver, are more likely to disperse from dense populations. This could help the t avoid detrimental sperm competition, because density is associated with the frequency of polyandry. However, no controlled experiments have been conducted to test these findings. Here, we confirm that carriers of the t haplotype are more dispersive, but we do not find this to depend on the local density. t-carriers with above-average body weight were particularly more likely to disperse than wild-type mice. t-carrying mice were also more explorative but not more active than wild-type mice. These results add experimental support to the previous observational finding that the t haplotype affects the dispersal phenotype in house mice, which supports the hypothesis that dispersal reduces the fitness costs of the t.
Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers
16833F. R. Finseth, T. C. Nelson and L. Fishman, PLOS Genetics, 17:e1009418. 2021-04-22 14:16:46.
Centromeres must mediate faithful chromosomal transmission during cell division and sexual reproduction, but both the DNA and protein components of centromeres diverge rapidly across species. The selfish centromere model argues that this paradoxical diversity results from a genetic conflict between centromeric DNA variants driving through female meiosis to gain over-transmission and kinetochore proteins co-evolving to re-establish Mendelian segregation. We use whole genome sequencing and genetic crossing experiments to demonstrate active evolutionary interactions between a selfish centromere and a key kinetochore protein (CenH3A) in the wildflower Mimulus guttatus. We show that both inter-specific and intra-population differences in CenH3A affect centromeric drive in hybrids, and that adaptive evolution of CenH3A has followed the recent and costly spread of the driver in a wild population. This work provides novel empirical support for the proposed antagonistic co-evolution of the DNA and protein components of centromeres, with important consequences for understanding cellular function, individual fitness, and species divergence.
Invasion and maintenance of meiotic drivers in populations of ascomycete fungi
17071I. Martinossi-Allibert, C. Veller, S. L. Ament-Velasquez, A. A. Vogan, C. Rueffler and H. Johannesson, Evolution, 20. 2021-03-25 14:37:42.
Meiotic drivers (MDs) are selfish genetic elements that are able to become overrepresented among the products of meiosis. This transmission advantage makes it possible for them to spread in a population even when they impose fitness costs on their host organisms. Whether an MD can invade a population, and subsequently reach fixation or coexist in a stable polymorphism, depends on the one hand on the biology of the host organism, including its life cycle, mating system, and population structure, and on the other hand on the specific fitness effects of the driving allele on the host. Here, we present a population genetic model for spore killing, a type of drive specific to fungi. We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with a nondriving allele. Our model can be adapted to different fungal life cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore-killing elements, Neurospora and Podospora. We discuss our results in the light of recent empirical findings for these two systems.
Meiotic drive does not cause condition-dependent reduction of the sexual ornament in stalk-eyed flies
17034S. R. Finnegan, M. Mondani, K. Fowler and A. Pomiankowski, Journal of Evolutionary Biology, 11. 2021-02-28 11:18:46.
Meiotic drive systems are associated with low-frequency chromosomal inversions. These are expected to accumulate deleterious mutations due to reduced recombination and low effective population size. We test this prediction using the 'sex-ratio' (SR) meiotic drive system of the Malaysian stalk-eyed fly Teleopsis dalmanni. SR is associated with a large inversion (or inversions) on the X chromosome. In particular, we study eyespan in males carrying the SR chromosome, as this trait is a highly exaggerated, sexually dimorphic trait, known to have heightened condition-dependent expression. Larvae were raised in low and high larval food stress environments. SR males showed reduced eyespan under the low and high stress treatments, but there was no evidence of a condition-dependent decrease in eyespan under high stress. Similar but more complex patterns were observed for female eyespan, with evidence of additivity under low stress and heterosis under high stress. These results do not support the hypothesis that reduced sexual ornament size in meiotic drive males is due to a condition-dependent response to the putative increase in mutation load. Instead, reduced eyespan likely reflects compensatory resource allocation to different traits in response to drive-mediated destruction of sperm.
Holocentric Chromosomes Probably Do Not Prevent Centromere Drive in Cyperaceae
16676M. Kratka, J. Smerda, K. Lojdova, P. Bures and F. Zedek, Frontiers in Plant Science, 12:9. 2021-02-19 14:30:42.
In response to these selfish centromeres, the histone protein CenH3, which recruits kinetochore components, adaptively evolves to restore chromosomal parity and counter the detrimental effects of centromere drive. Holocentric chromosomes, whose kinetochores are assembled along entire chromosomes, have been hypothesized to prevent expanded centromeres from acquiring a selective advantage and initiating centromere drive. In such a case, CenH3 would be subjected to less frequent or no adaptive evolution. Using codon substitution models, we analyzed 36 CenH3 sequences from 35 species of the holocentric family Cyperaceae. We found 10 positively selected codons in the CenH3 gene [six codons in the N-terminus and four in the histone fold domain (HFD)] and six branches of its phylogeny along which the positive selection occurred. One of the positively selected codons was found in the centromere targeting domain (CATD) that directly interacts with DNA and its mutations may be important in centromere drive suppression. The frequency of these positive selection events was comparable to the frequency of positive selection in monocentric clades with asymmetric female meiosis. Taken together, these results suggest that preventing centromere drive is not the primary adaptive role of holocentric chromosomes, and their ability to suppress it likely depends on their kinetochore structure in meiosis.
Widespread haploid-biased gene expression enables sperm-level natural selection
16009K. Bhutani, K. Stansifer, S. Ticau, L. Bojic, A.-C. Villani, J. Slisz, C. M. Cremers, C. Roy, J. Donovan, B. Fiske and R. C. Friedman, Science, eabb1723. 2021-01-14 14:15:08.
Here, we show that a large class of mammalian genes are not completely shared across these bridges. We term these genes “genoinformative markers” (GIMs) and show that a subset can act as selfish genetic elements that spread alleles unevenly through murine, bovine, and human populations. We identify evolutionary pressure to avoid conflict between sperm and somatic function as GIMs are enriched for testis-specific gene expression, paralogs, and isoforms.
Whole-genome resequencing reveals loci with allelic transmission ratio distortion in F1 chicken population
16106P. Ren, F. Deng, S. Chen, J. Ran, J. Li, L. Yin, Y. Wang, H. Yin, Q. Zhu and Y. Liu, Molecular Genetics and Genomics, 2021-01-02 15:31:28.
In this study, whole-genome resequencing technology was applied to reveal TRD loci in chicken by constructing a full-sib F1 hybrid population. Through the whole-genome resequencing data of two parents (30 ×) and 38 offspring (5 ×), we detected a total of 2850 TRD SNPs (p-adj < 0.05) located within 400 genes showing TRD, and all of them were unevenly distributed on macrochromosomes and microchromosomes. Our findings suggested that TRD in the chicken chromosome 16 might play an important role in chicken immunity and disease resistance and the MYH1F with significant TRD and allele-specific expression could play a key role in the fast muscle development. In addition, functional enrichment analyses revealed that many genes (e.g., TGFBR2, TGFBR3, NOTCH1, and NCOA1) with TRD were found in the significantly enriched biological process and InterPro terms in relation to embryonic lethality and germline selection. Our results suggested that TRD is considerably prevalent in the chicken genome and has functional implications.
RNA editing controls meiotic drive by a Neurospora Spore killer
24344N. A. Rhoades and T. M. Hammond, bioRxiv, 2020.12.30.424869. 2021-01-01 10:39:57.
Neurospora Sk-2 is a complex meiotic drive element that is transmitted to offspring through sexual reproduction in a biased manner. Sk-2’s biased transmission mechanism involves spore killing, and recent evidence has demonstrated that spore killing is triggered by a gene called rfk-1. However, a second gene, rsk, is also critically important for meiotic drive by spore killing because it allows offspring with an Sk-2 genotype to survive the toxic effects of rfk-1. Here, we present evidence demonstrating that rfk-1 encodes two protein variants: a 102 amino acid RFK-1A and a 130 amino acid RFK-1B, but only RFK-1B is toxic. We also show that expression of RFK-1B requires an early stop codon in rfk-1 mRNA to undergo adenosine-to-inosine (A-to-I) mRNA editing. Finally, we demonstrate that RFK-1B is toxic when expressed within vegetative tissue of Spore killer sensitive (SkS) strains, and that this vegetative toxicity can be overcome by co-expressing Sk-2’s version of RSK. Overall, our results demonstrate that Sk-2 uses RNA editing to control when its spore killer is produced, and that the primary killing and resistance functions of Sk-2 can be conferred upon an SkS strain by the transfer of only two genes.Competing Interest StatementThe authors have declared no competing interest.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages
15219J. F. Hughes, H. Skaletsky, T. Pyntikova, N. Koutseva, T. Raudsepp, L. G. Brown, D. W. Bellott, T.-J. Cho, S. Dugan-Rocha, Z. Khan, C. Kremitzki, C. Fronick, T. A. Graves-Lindsay, L. Fulton, W. C. Warren, R. K. Wilson, E. Owens, J. E. Womack, W. J. Murphy, Genome Research, 2020-11-18 16:58:55.
Here, we provide evidence that suppression of X–Y crossing-over unleashed a second dynamic: selfish X–Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X–Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X–Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
The bull Y chromosome has evolved to bully its way into gametes
15217Whitehead Institute for Biomedical Research, Phys Org, 2020-11-18 16:54:40.
In a new study, published Nov. 18 in the journal Genome Research, scientists in the lab of Whitehead Institute Member David Page present the first ever full, high-resolution sequence of the Y chromosome of a Hereford bull. The research, more than a decade in the making, suggests that bulls' Y chromosomes have evolved dozens of copies of the same genes in a selfish attempt to make more males—a move that is countered in the female-determining X chromosome. This insight into the forces that govern sex chromosome behavior and evolution will help scientists in Page's lab study genetic differences between males and females and how they play out in health and disease across every part of the body, Page added.
A test for meiotic drive in hybrids between Australian and Timor zebra finches
15133U. Knief, W. Forstmeier, Y. Pei, J. Wolf and B. Kempenaers, Ecology and Evolution, 2020-11-03 16:16:43.
We did not find evidence for meiotic driver loci on specific chromosomes. However, we observed a weak overall transmission bias toward Timor alleles at centromeres in females (transmission probability of Australian alleles of 47%, nominal p = 6 ? 10?5). While this is in line with the centromere drive theory, it goes against the expectation that the subspecies with the larger effective population size (i.e., the Australian zebra finch) should have evolved the more potent meiotic drivers. We thus caution against interpreting our finding as definite evidence for centromeric drive. Yet, weak centromeric meiotic drivers may be more common than generally anticipated and we encourage further studies that are designed to detect also small effect meiotic drivers.
Cellular mechanisms regulating synthetic sex ratio distortion in the Anopheles gambiae germline
14790R. E. Haghighat-Khah, A. Sharma, M. R. Wunderlich, G. Morselli, L. A. Marston, C. Bamikole, A. Hall, N. Kranjc, C. Taxiarchi, I. Sharakhov and R. Galizi, Pathogens and Global Health, 114:370-378. 2020-10-20 20:24:19.
Meiotic cleavage of rDNA repeats, located in the sex chromosomes of A. gambiae SD males, affects the competitiveness of mature sperm to fertilize the female oocyte.
Selfish genetic elements and male fertility
15183R. L. Verspoor, T. A. R. Price and N. Wedell, Philosophical Transactions of the Royal Society B-Biological Sciences, 375:7. 2020-10-20 14:40:03.
Selfish genetic elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here, we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex ratios and in particular reducing sperm-competitive success of SGE-carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely. This article is part of the theme issue 'Fifty years of sperm competition'.
Engineering the Composition and Fate of Wild Populations with Gene Drive
14731B. A. Hay, G. Oberhofer and M. Guo, Annual Review of Entomology, 2020-10-09 15:37:03.
We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
Maternal Transmission Ratio Distortion in Two Iberian Pig Varieties
14894M. Vazquez-Gomez, M. M. de Hijas-Villalba, L. Varona, N. Ibanez-Escriche, J. P. Rosas, S. Negro, J. L. Noguera and J. Casellas, Genes, 11:16. 2020-09-05 13:58:00.
Although TRD can be a confounding factor in genetic mapping studies, this phenomenon remains mostly unknown in pigs, particularly in traditional breeds (i.e., the Iberian pig). We aimed to describe the maternal TRD prevalence and its genomic distribution in two Iberian varieties. No strong evidence of biological effects was found in genes with TRDLs. However, some biological processes could be affected by TRDLs, such as embryogenesis at different levels and lipid metabolism. These findings could provide useful insight into the genetic mechanisms to improve the swine industry, particularly in traditional breeds.
Survival of the fit-ish
13897Stowers Institute for Medical Research, Science Daily, 2020-08-17 13:27:56.
In a paper published online August 13, 2020, in eLife, members of the Zanders lab explain how it could be possible that meiotic drivers persist in the population, even as they kill off many would-be hosts. It turns out that S. pombe can employ variants of other genes to help suppress the negative effect of meiotic drivers, albeit at a cost to fitness.
Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers
13899M. A. Bravo Núñez, I. M. Sabbarini, L. E. Eide, R. L. Unckless and S. E. Zanders, eLife, 9:e57936. 2020-08-13 13:30:44.
Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.
Maternal effect killing by a supergene controlling ant social organization
12741A. Avril, J. Purcell, S. Béniguel and M. Chapuisat, Proceedings of the National Academy of Sciences, 2020-07-07 13:29:50.
Supergenes are clusters of linked loci producing complex alternative phenotypes. In a series of experiments, we demonstrate that a supergene controlling ant social organization distorts Mendel’s laws to enhance its transmission to adult offspring. One supergene haplotype is specific to multiple-queen colonies. This haplotype kills half of the offspring from heterozygous mothers—all eggs that do not inherit the haplotype fail to hatch. Hence, the haplotype associated with multiple-queen colonies is a selfish genetic element favoring its transmission to the detriment of the alternate haplotype associated with single-queen colonies. Selfish gene drive by a large group of linked genes impacts the social organization of ant colonies, which illustrates the intricate multilevel effects of supergenes.Supergenes underlie striking polymorphisms in nature, yet the evolutionary mechanisms by which they arise and persist remain enigmatic. These clusters of linked loci can spread in populations because they captured coadapted alleles or by selfishly distorting the laws of Mendelian inheritance. Here, we show that the supergene haplotype associated with multiple-queen colonies in Alpine silver ants is a maternal effect killer. All eggs from heterozygous queens failed to hatch when they did not inherit this haplotype. Hence, the haplotype specific to multiple-queen colonies is a selfish genetic element that enhances its own transmission by causing developmental arrest of progeny that do not carry it. At the population level, such transmission ratio distortion favors the spread of multiple-queen colonies, to the detriment of the alternative haplotype associated with single-queen colonies. Hence, selfish gene drive by one haplotype will impact the evolutionary dynamics of alternative forms of colony social organization. This killer hidden in a social supergene shows that large nonrecombining genomic regions are prone to cause multifarious effects across levels of biological organization.
Invasion and maintenance of spore killers in populations of ascomycete fungi
15129I. Martinossi-Allibert, C. Veller, S. L. Ament-Velásquez, A. A. Vogan, C. Rueffler and H. Johannesson, bioRxiv, 2020.04.06.026989. 2020-06-30 16:08:48.
We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with the non-driving allele. Our model can be adapted to different fungal life-cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore killing elements, Podospora and Neurospora. We discuss our results in the light of recent empirical findings for these two systems.Competing Interest StatementThe authors have declared no competing interest.
Can natural gene drives be part of future fungal pathogen control strategies in plants?
12564D. M. Gardiner, A. Rusu, L. Barrett, G. C. Hunter and K. Kazan, New Phtologist, 2020-06-28 19:10:13.
Globally, fungal pathogens cause enormous crop losses and current control practices are not always effective, economical or environmentally sustainable. Tools enabling genetic management of wild pathogen populations could potentially solve many problems associated with plant diseases. A natural gene drive from a heterologous species can be used in the globally important cereal pathogen, Fusarium graminearum, to remove pathogenic traits from contained populations of the fungus. The gene drive element became fixed in a freely crossing populations in only three generations. Repeat induced point mutation (RIP), a natural genome defence mechanism in fungi that causes C to T mutations during meiosis in highly similar sequences, may be useful to recall the gene drive following release, should a failsafe mechanism be required. We propose that gene drive technology is a potential tool to control plant pathogens once its efficacy is demonstrated under natural settings.
Analysis of a Strong Suppressor of Segregation Distorter inDrosophila melanogaster
14264R. G. Temin, Genetics, 215:1085-1105. 2020-06-19 14:59:33.
These studies highlight the polygenic nature of distortion and its dependence on a constellation of positive and negative modifiers, provide insight into the stability of Mendelian transmission in natural populations even when a drive system arises, and pave the way for molecular characterization ofSu(SD)whose identity should reveal new information about the mechanism of distortion.
Meiotic drive
12538A. N. Srinivasa and S. E. Zanders, Current Biology, 30:R627-R629. 2020-06-08 15:35:32.
What is meiotic drive? Diploid organisms, like you, have two copies of each autosomal chromosome, one from each parent. Sometimes organisms are heterozygous at a given region, meaning they carry different copies (or alleles) of the DNA sequence on the two homologous chromosomes. Generally, the alternative alleles at a given site have an equal chance of being transmitted into the next generation by way of gametes (like sperm or eggs). A man with XY sex chromosomes, for example, will generate an equal number of X-bearing and Y-bearing sperm. This will lead him to father male and female offspring with equal probability. This Mendelian allele transmission constitutes one of the foundational laws of genetics. Meiotic drivers are alleles that break this law and force their transmission into more than half or sometimes even all of the progeny.
A Protamine Knockdown Mimics the Function of Sd in Drosophila melanogaster
12536L. F. Gingell and J. R. McLean, G3-Genes Genomes Genetics, 10:2111-2115. 2020-06-01 15:29:52.
Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster. This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD+ males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsp(s) locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD+ males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previously, we have shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. Herein, we show that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion
The Y Chromosome as a Battleground for Intragenomic Conflict
11962D. Bachtrog, Trends in Genetics, 2020-05-21 18:10:11.
Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.
Recessive Z-linked lethals and the retention of haplotype diversity in a captive butterfly population
11972I. J. Saccheri, S. Whiteford, C. J. Yung and A. E. van't Hof, Heredity, 2020-05-13 18:21:56.
Sex chromosomes are predicted to harbour elevated levels of sexually antagonistic variation due to asymmetries in the heritability of recessive traits in the homogametic versus heterogametic sex.
The Enterprise: A massive transposon carrying Spokt meiotic drive genes
15127A. A. Vogan, S. L. Ament-Velásquez, E. Bastiaans, O. Wallerman, S. J. Saupe, A. Suh and H. Johannesson, bioRxiv, 2020.03.25.007153. 2020-04-28 16:03:56.
Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite.
Selfish genes and sexual selection: the impact of genomic parasites on host reproduction
11970N. Wedell, Journal of Zoology, 311:1-12. 2020-04-08 18:18:42.
Selfish genetic elements (SGEs) such as replicating mobile elements, segregation distorters and maternally inherited endosymbionts, bias their transmission success relative to the rest of the genome to increase in representation in subsequent generations. As such, they generate conflict with the rest of the genome. Such intragenomic conflict is also a hallmark of sexually antagonistic (SA) alleles, which are shared genes between the sexes but that have opposing fitness effects when expressed in males and females. However, whilst both SGEs and SA alleles are recognized as common and potent sources of genomic conflict, the realization that SGEs can also generate sexually antagonistic selection and contribute to sexual conflict in addition to generate sexual selection is largely overlooked. Here, I show that SGEs frequently generate sex-specific selection and outline how SGEs that are associated with compromised male fertility can shape female mating patterns, play a key role in the dynamics of sex-determination systems and likely be an important source of sexually antagonistic genetic variation. Given the prevalence of SGEs, their contribution to sexual conflict is likely to be greatly overlooked.
Strategies for Achieving Gene Drive – Gonotaxis
11408GeneConvene Global Collaborative, 2020-03-27 13:46:56.
This video explains how there are three strategies for achieving gene drive and focuses on one, gonotaxis. Gonotaxis is explained and illustrated. While well-described in various plants and animals, gene drive researchers and technology developers have not recreated gonotaxis using transgenic approaches.
Gene Drive – The Concept Explained
11402GeneConvene Global Collaborative, 2020-03-20 12:59:44.
This short video is intended to serve as a short tutorial that explains the general idea of 'drive' or 'gene drive' in the context of genetics. It provides the viewer with a basic understanding of the key genetic processes underlying the patterns of inheritance with which most people of familiar and explains how these processes are involved in gene drive. This video focuses on genetics and not applications of gene drive technologies and associated issues.
Modeling the impacts of a simple meiotic gene drive on small, homeostatic populations
7956K. R. Pilkiewicz and M. L. Mayo, Physical Review E, 101:11. 2020-02-18 13:43:10.
Gene drives offer unprecedented control over the fate of natural ecosystems by leveraging non-Mendelian inheritance mechanisms to proliferate synthetic genes across wild populations. However, these benefits are offset by a need to avoid the potentially disastrous consequences of unintended ecological interactions. The efficacy of many gene-editing drives has been brought into question due to predictions that they will inevitably be thwarted by the emergence of drive-resistant mutations, but these predictions derive largely from models of large or infinite populations that cannot be driven to extinction faster than mutations can fixate. To address this issue, we characterize the impact of a simple, meiotic gene drive on a small, homeostatic population whose genotypic composition may vary due to the stochasticity inherent in natural mating events (e.g., partner choice, number of offspring) or the genetic inheritance process (e.g., mutation rate, gene drive fitness). To determine whether the ultimate genotypic fate of such a population is sensitive to such stochastic fluctuations, we compare the results of two dynamical models: a deterministic model that attempts to predict how the genetics of an average population evolve over successive generations, and an agent-based model that examines how stable these predictions are to fluctuations. We find that, even on average, our stochastic model makes qualitatively distinct predictions from those of the deterministic model, and we identify the source of these discrepancies as a dynamic instability that arises at short times, when genetic diversity is maximized as a consequence of the gene drive's rapid proliferation. While we ultimately conclude that extinction can only beat out the fixation of drive-resistant mutations over a limited region of parameter space, the reason for this is more complex than previously understood, which could open new avenues for engineered gene drives to circumvent this weakness.
Dramatically diverse Schizosaccharomyces pombe wtf meiotic drivers all display high gamete-killing efficiency
7943M. A. Bravo Núñez, I. M. Sabbarini, M. T. Eickbush, Y. Liang, J. J. Lange, A. M. Kent and S. E. Zanders, PLOS Genetics, 16:e1008350. 2020-02-07 20:35:38.
During gametogenesis, the two gene copies at a given locus, known as alleles, are each transmitted to 50% of the gametes (e.g. sperm). However, some alleles cheat so that they are found in more than the expected 50% of gametes, often at the expense of fertility. This selfish behavior is known as meiotic drive. Some members of the wtf gene family in the fission yeast Schizosaccharomyces pombe kill the gametes (spores) that do not inherit them, resulting in meiotic drive favoring the wtf allele. Other wtf genes act as suppressors of drive. However, the wtf gene family is diverse and only a small subset of the genes has been characterized. Here we analyze the functions of other members of this gene family and found eight new drivers as well as three new suppressors of drive. Surprisingly, we find that drive is relatively insensitive to changes in wtf gene sequence as highly diverged wtf genes execute gamete killing with similar efficiency. Finally, we also find that the expression and localization of some Wtf proteins are distinct from those of known drivers and suppressors, suggesting that these proteins may have non-meiotic drive functions.
Progress towards engineering gene drives for population control
7937R. R. Raban, J. M. Marshall and O. S. Akbari, The Journal of Experimental Biology, 223:jeb208181. 2020-02-07 20:21:50.
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the potential to revolutionize vector-borne disease control. This suite of technologies has advanced rapidly in recent years as a result of the availability of new, more efficient gene editing technologies. Gene drives can favorably bias the inheritance of a linked disease-refractory gene, which could possibly be exploited (i) to generate a vector population incapable of transmitting disease or (ii) to disrupt an essential gene for viability or fertility, which could eventually eliminate a population. Importantly, gene drives vary in characteristics such as their transmission efficiency, confinability and reversibility, and their potential to develop resistance to the drive mechanism. Here, we discuss recent advancements in the gene drive field, and contrast the benefits and limitations of a variety of technologies, as well as approaches to overcome these limitations. We also discuss the current state of each gene drive technology and the technical considerations that need to be addressed on the pathway to field implementation. While there are still many obstacles to overcome, recent progress has brought us closer than ever before to genetic-based vector modification as a tool to support vector-borne disease elimination efforts worldwide.
An introgressed gene causes meiotic drive in Neurospora sitophila
15125J. Svedberg, A. A. Vogan, N. A. Rhoades, D. Sarmarajeewa, D. J. Jacobson, M. Lascoux, T. M. Hammond and H. Johannesson, bioRxiv, 2020.01.29.923946. 2020-01-30 15:58:21.
In this study, we identify the gene responsible for spore killing in Sk-1 by generating both long and short-read genomic data and by using these data to perform a genome wide association test. By phylogenetic analysis, we demonstrate that the gene is likely to have been introgressed from the closely related species N. hispaniola, and we identify three subclades of N. sitophila, one where Sk-1 is fixed, another where Sk-1 is absent, and a third where both killer and sensitive strain are found. We show that spore killing can be suppressed through an RNA interference based genome defense pathway known as meiotic silencing by unpaired DNA.
Autosomal suppression and fitness costs of an old driving X chromosome in Drosophila testacea
7363G. Keais, S. Lu and S. Perlman, Journal of Evolutionary Biology, 2020-01-28 21:58:18.
Driving X chromosomes (XDs) are meiotic drivers that bias their own transmission through males by killing Y-bearing gametes. These chromosomes can in theory spread rapidly in populations and cause extinction, but many are found as balanced polymorphisms or as ?cryptic? XDs shut down by drive suppressors. The relative likelihood of these outcomes, as well as the evolutionary pathways through which they come about, are not well-understood. An XD was recently discovered in the mycophagous fly, Drosophila testacea, presenting the opportunity to compare this XD with the well-studied XD of its sister species, Drosophila neotestacea. Comparing features of independently evolved XDs in young sister species is a promising avenue towards understanding how XDs and their counteracting forces change over time. In contrast to the XD of D. neotestacea, we find that the XD of D. testacea is old, with its origin predating the radiation of three species: D. testacea, D. neotestacea, and their shared sister species, Drosophila orientacea. Motivated by the suggestion that older XDs should be more deleterious to carriers, we assessed the effect of the XD on both male and female fertility. Unlike what is known from D. neotestacea, we found a strong fitness cost in females homozygous for the XD in D. testacea: a large proportion of homozygous females failed to produce offspring after being housed with males for several days. Our male fertility experiments show that while XD male fertility is lower under sperm depleting conditions, XD males have comparable fertility to males carrying a standard X chromosome under a free mating regime, which may better approximate conditions in wild populations of D. testacea. Lastly, we demonstrate the presence of autosomal suppression of X chromosome drive. Our results provide support for a model of XD evolution where the dynamics of young XDs are governed by fitness consequences in males, whereas in older XD systems, both suppression and fitness consequences in females likely supersede male fitness costs.
A selfish genetic element linked to increased lifespan impacts metabolism in female house mice
5652Lopes, P. C. and A. K. Lindholm, The Journal of Experimental Biology, 2019:212704. 2019-12-17 18:01:15.
Gene drive systems can lead to the evolution of traits that further enhance the transmission of the driving element. In gene drive, one allele is transmitted to offspring at a higher frequency than the homologous allele. This has a range of consequences, which generally include a reduction in fitness of the carrier of the driving allele, making such systems “selfish”. The t haplotype is one such driver, found in house mice. It is linked to a reduction in litter size in matings among heterozygous animals, but also to increased lifespan in wild females that carry it. Here, we tested whether carrying the t haplotype was associated with altered resting metabolic rate (RMR). We show that females carrying the t haplotype decrease RMR as they increase in size, compared to wildtype females or males of either genotype. Our study elucidates a plausible mechanism by which a selfish genetic element increases lifespan.
Maintenance of fertility in the face of meiotic drive
5622Meade, L., S. Finnegan, R. Kad, K. Fowler and A. Pomiankowsk, The American Naturalist, 2019:2019. 2019-12-17 16:32:30.
Selfish genetic elements that gain a transmission advantage through the destruction of sperm have grave implications for drive male fertility. In the X-linked SR meiotic drive system of a stalk-eyed fly, we found that drive males have greatly enlarged testes and maintain high fertility despite the destruction of half their sperm, even when challenged with fertilizing large numbers of females. Conversely, we observed reduced allocation of resources to the accessory glands that probably explains the lower mating frequency of SR males. Body size and eyespan were also reduced, which are likely to impair viability and pre-copulatory success. We discuss the potential evolutionary causes of these differences between drive and standard males.
An assessment of the immune costs associated with meiotic drive elements in Drosophila
5614Lea, J. K. and R. L. Unckless, Proceedings of the Royal Society B: Biological Sciences, 286:20191534. 2019-12-17 16:21:00.
Most organisms are constantly adapting to pathogens and parasites that exploit their host for their own benefit. Less studied, but perhaps more ubiquitous, are intragenomic parasites or selfish genetic elements. These include transposable elements, selfish B chromosomes and meiotic drivers that promote their own replication without regard to fitness effects on hosts. Therefore, intragenomic parasites are also a constant evolutionary pressure on hosts. Gamete-killing meiotic drive elements are often associated with large chromosomal inversions that reduce recombination between the drive and wild-type chromosomes. This reduced recombination is thought to reduce the efficacy of selection on the drive chromosome and allow for the accumulation of deleterious mutations. We tested whether gamete-killing meiotic drive chromosomes were associated with reduced immune defence against two bacterial pathogens in three species of Drosophila. We found little evidence of reduced immune defence in lines with meiotic drive. One line carrying the Drosophila melanogaster autosomal Segregation Distorter did show reduced defence, but we were unable to attribute that reduced defence to either genotype or immune gene expression differences. Our results suggest that though gamete-killing meiotic drive chromosomes probably accumulate deleterious mutations, those mutations do not result in reduced capacity for immune defence.
Genetic Control of Mosquitoes
5588Alphey, L., Annual Review of Entomology, 59:205-224. 2019-12-16 19:01:55.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
An X-linked meiotic drive allele has strong, recessive fitness costs in female Drosophila pseudoobscura
6171W. Larner, T. Price, L. Holman and N. Wedell, Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-11-27 18:44:20.
Selfish 'meiotic drive' alleles are transmitted to more than 50% of offspring, allowing them to rapidly invade populations even if they reduce the fitness of individuals carrying them. Theory predicts that drivers should either fix or go extinct, yet some drivers defy these predictions by persisting at low, stable frequencies for decades. One possible explanation for this discrepancy is that drivers are especially costly when homozygous, although empirical tests of this idea are rare and equivocal. Here, we measure the fitness of female Drosophila pseudoobscura carrying zero, one or two copies of the X-linked driver sex ratio (SR). SR had strong negative effects on female offspring production and the probability of reproductive failure, and these effects were largely similar across four genetic backgrounds. SR was especially costly when homozygous. We used our fitness measurements to parametrize a population genetic model, and found that the female fitness costs observed here can explain the puzzlingly low allele frequency of SR in nature. We also use the model to show how spatial variation in female mating behaviour, fitness costs of SR and the reduced siring success of SR males can jointly explain the north-south cline in SR frequencies across North America.
Effects of a male meiotic driver on male and female transcriptomes in the house mouse
6639A. Lindholm, A. Sutter, S. Kunzel, D. Tautz and H. Rehrauer, Proceedings of the Royal Society B-Biological Sciences, 286:1-8. 2019-11-13 20:18:05.
Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.
Meiotic drive mechanisms: lessons from Drosophila
6021C. Courret, C.-H. Chang, K. H.-C. Wei, C. Montchamp-Moreau and A. M. Larracuente, Proceedings of the Royal Society B: Biological Sciences, 286:20191430. 2019-10-23 20:28:42.
Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in the Drosophila genus. Recent studies in Drosophila have provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers in Drosophila species. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work in Drosophila has made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.
Does meiotic drive alter male mate preference?
7960S. R. Finnegan, L. Nitsche, M. Mondani, M. F. Camus, K. Fowler and A. Pomiankowski, Behavioral Ecology, 13:194-201. 2019-10-20 14:14:20.
Male mate preferences have been demonstrated across a range of species, including the Malaysian stalk-eyed fly, Teleopsis dalmanni. This species is subject to sex-ratio (SR), an X-linked male meiotic driver, which causes the dysfunction of Y-sperm and the production of all-female broods. While there has been work considering female avoidance of meiotic drive males, the mating decisions of drive-bearing males have not been considered previously. Drive males may be less able to bear the cost of choice as SR is associated with a low-frequency inversion that causes reduced organismal fitness. Drive males may also experience weaker selection for preference maintenance if they are avoided by females. Using binary choice trials, across two experiments, we confirmed male preference for large (fecund) females but found no evidence that the strength of male preference differs between drive and standard males. We showed that large eyespan males displayed strong preference for large females, whereas small eyespan males showed no preference. Taken together, these results suggest that, even though meiotic drive is associated with lower genetic quality, it does not directly interfere with male mate preference among available females. However, as drive males tend to have smaller eyespan (albeit only similar to 5% on average), this will to a minor extent weaken their strength of preference.
Fitness consequences of the selfish supergene Segregation Distorter
6641H. W. S. Wong and L. Holman, Journal of Evolutionary Biology, 33:89-100. 2019-10-11 20:21:24.
Segregation distorters are selfish genetic elements that subvert Mendelian inheritance, often by destroying gametes that do not carry the distorter. Simple theoretical models predict that distorter alleles will either spread to fixation or stabilize at some high intermediate frequency. However, many distorters have substantially lower allele frequencies than predicted by simple models, suggesting that key sources of selection remain to be discovered. Here, we measured the fitness of Drosophila melanogaster adults and juveniles carrying zero, one or two copies of three different variants of the naturally occurring supergene Segregation Distorter (SD), in order to investigate why SD alleles remain relatively rare within populations despite being preferentially inherited. First, we show that the three SD variants differ in the severity and dominance of the fitness costs they impose on individuals carrying them. Second, SD-carrying parents produced less fit offspring in some crosses, independent of offspring genotype, indicating that SD alleles can have nongenetic, transgenerational costs in addition to their direct costs. Third, we found that SD carriers sometimes produce a biased offspring sex ratio, perhaps due to off-target effects of SD on the sex chromosomes. Finally, we used a theoretical model to investigate how sex ratio and transgenerational effects alter the population genetics of distorter alleles; accounting for these additional costs helps to explain why real-world segregation distorter alleles are rarer than predicted.
Standard deviations: The biological bases of transmission ratio distortion
6179L. Fishman and M. McIntosh, Annual Review of Genetics, 53:347-372. 2019-09-10 18:59:40.
The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms.
A natural gene drive system influences bovine tuberculosis susceptibility in African buffalo: Possible implications for disease management
6038P. van Hooft, W. M. Getz, B. J. Greyling and A. D. S. Bastos, PLoS One, 14:e0221168. 2019-09-04 20:57:09.
Bovine tuberculosis (BTB) is endemic to the African buffalo (Syncerus caffer) of Hluhluwe-iMfolozi Park (HiP) and Kruger National Park, South Africa. In HiP, the disease has been actively managed since 1999 through a test-and-cull procedure targeting BTB-positive buffalo. Prior studies in Kruger showed associations between microsatellite alleles, BTB and body condition. A sex chromosomal meiotic drive, a form of natural gene drive, was hypothesized to be ultimately responsible. These associations indicate high-frequency occurrence of two types of male-deleterious alleles (or multiple-allele haplotypes). One type negatively affects body condition and BTB resistance in both sexes. The other type has sexually antagonistic effects: negative in males but positive in females. Here, we investigate whether a similar gene drive system is present in HiP buffalo, using 17 autosomal microsatellites and microsatellite-derived Y-chromosomal haplotypes from 401 individuals, culled in 2002–2004. We show that the association between autosomal microsatellite alleles and BTB susceptibility detected in Kruger, is also present in HiP. Further, Y-haplotype frequency dynamics indicated that a sex chromosomal meiotic drive also occurred in HiP. BTB was associated with negative selection of male-deleterious alleles in HiP, unlike positive selection in Kruger. Birth sex ratios were female-biased. We attribute negative selection and female-biased sex ratios in HiP to the absence of a Y-chromosomal sex-ratio distorter. This distorter has been hypothesized to contribute to positive selection of male-deleterious alleles and male-biased birth sex ratios in Kruger. As previously shown in Kruger, microsatellite alleles were only associated with male-deleterious effects in individuals born after wet pre-birth years; a phenomenon attributed to epigenetic modification. We identified two additional allele types: male-specific deleterious and beneficial alleles, with no discernible effect on females. Finally, we discuss how our findings may be used for breeding disease-free buffalo and implementing BTB test-and-cull programs.
Combinations of Spok genes create multiple meiotic drivers in Podospora
7240A. A. Vogan, S. L. Ament-Velásquez, A. Granger-Farbos, J. Svedberg, E. Bastiaans, A. J. M. Debets, V. Coustou, H. Yvanne, C. Clavé, S. J. Saupe and H. Johannesson, eLife, 8:e46454. 2019-07-26 15:53:58.
Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74–167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.
A family of killers
7238M. De Carvalho and S. E. Zanders, eLife, 8:e49211. 2019-07-26 15:50:06.
Spok genes are meiotic drivers that increase their own chances of transmission by killing gametes that do not inherit them.
Sex-ratio meiotic drive shapes the evolution of the Y chromosome in Drosophila simulans
6174Q. Helleu, C. Courret, D. Ogereau, K. L. Burnham, N. Chaminade, M. Chakir, S. Aulard and C. Montchamp-Moreau, Molecular Biology and Evolution, 36:2668-2681. 2019-07-10 18:50:56.
The recent emergence and spread of X-linked segregation distorters-called "Paris" system-in the worldwide species Drosophila simulans has elicited the selection of drive-resistant Y chromosomes. Here, we investigate the evolutionary history of 386 Y chromosomes originating from 29 population samples collected over a period of 20 years, showing a wide continuum of phenotypes when tested against the Paris distorters, from high sensitivity to complete resistance (males sire similar to 95% to similar to 40% female progeny). Analyzing around 13 kb of Y-linked gene sequences in a representative subset of nine Y chromosomes, we identified only three polymorphic sites resulting in three haplotypes. Remarkably, one of the haplotypes is associated with resistance. This haplotype is fixed in all samples from Sub-Saharan Africa, the region of origin of the drivers. Exceptionally, with the spread of the drivers in Egypt and Morocco, we were able to record the replacement of the sensitive lineage by the resistant haplotype in real time, within only a few years. In addition, we performed in situ hybridization, using satellite DNA probes, on a subset of 21 Y chromosomes from six locations. In contrast to the low molecular polymorphism, this revealed extensive structural variation suggestive of rapid evolution, either neutral or adaptive. Moreover, our results show that intragenomic conflicts can drive astonishingly rapid replacement of Y chromosomes and suggest that the emergence of Paris segregation distorters in East Africa occurred less than half a century ago.
A century of bias in genetics and evolution
6691L. D. Hurst, Heredity, 123:33-44. 2019-06-12 17:55:20.
Mendel proposed that the heritable material is particulate and that transmission of alleles is unbiased. An assumption of unbiased transmission was necessary to show how variation can be preserved in the absence of selection, so overturning an early objection to Darwinism. In the second half of the twentieth century, it was widely recognised that even strongly deleterious alleles can invade if they have strongly biased transmission (i.e. strong segregation distortion). The spread of alleles with distorted segregation can explain many curiosities. More recently, the selectionist-neutralist duopoly was broken by the realisation that biased gene conversion can explain phenomena such as mammalian isochore structures. An initial focus on unbiased transmission in 1919, has thus given way to an interest in biased transmission in 2019. A focus on very weak bias is now possible owing to technological advances, although technical biases may put a limit on resolving power. To understand the relevance of weak bias we could profit from having the concept of the effectively Mendelian allele, a companion to the effectively neutral allele. Understanding the implications of unbiased and biased transmission may, I suggest, be a good way to teach evolution so as to avoid psychological biases.
Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report
11581M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne, North Carolina State University, 2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.
Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating
11202J. J. Bull, C. H. Remien and S. M. Krone, Evolution Medicine and Public Health, 2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).
Identification of fk-1;, a Meiotic Driver Undergoing RNA Editing in Neurospora
15131N. A. Rhoades, A. M. Harvey, D. A. Samarajeewa, J. Svedberg, A. Yusifov, A. Abusharekh, P. Manitchotpisit, D. W. Brown, K. J. Sharp, D. G. Rehard, J. Peters, X. Ostolaza-Maldonado, J. Stephenson, P. K. T. Shiu, H. Johannesson and T. M. Hammond, Genetics, 212:93. 2019-05-03 16:12:34.
These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1’s MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.
Genetic pest management technologies to control invasive rodents
11576D. Kanavy and D. Threadgill, Island invasives: scaling up to meet the challenge, 2019-03-05 15:20:05.
Many strategies exist to manage invasive pests on islands, ranging from poison to trapping, with varying degrees of success. Genetic technologies are increasingly being applied to insect pests, but so far, not to vertebrates. We are implementing a genetic strategy to eradicate invasive mouse populations as another tool for pest control. Mus musculus, the common house mouse, is one of the most widespread invasive species. Mice threaten human health, agriculture, and biodiversity on many islands, particularly seabirds. Seabirds are endangered indirectly through competition for resources or predators being attracted by the mice or directly with mice attacking chicks and eggs. Rodenticides are the most common method of eradicating mice, but their use leads to poisoning of non-target species and has limited efficacy against mice. An approach that could eliminate non-target species impact would be to engineer daughterless mice linked to a gene drive system for self-sustained propagation. For this project, we have investigated exploiting a naturally occurring gene drive, the t-complex. Using the t w2 haplotype of the t-complex, we observed the t w2 haplotype being transmitted to offspring with a transmission distortion ratio of 95.3%. The daughterless phenotype is being accomplished by inserting the Sry gene (male sex-determining gene) into an autosome containing the tw2 haplotype via CRISPR/Cas9 gene editing. The presence of Sry will induce testis formation, regardless of the sex chromosomes naturally inherited. When Sry is inserted into the t-complex, the desired gene will spread through the population, eliminating female offspring. This model system will support studies to evaluate the effectiveness of crashing an invasive population without adversely affecting other
Meiotic drive shapes rates of karyotype evolution in mammals
5921Blackmon, H., J. Justison, I. Mayrose and E. E. Goldberg, Evolution, 73:511-523. 2019-03-01 16:47:19.
Chromosome number is perhaps the most basic characteristic of a genome, yet generalizations that can explain the evolution of this trait across large clades have remained elusive. Using karyotype data from over 1000 mammals, we developed and applied a phylogenetic model of chromosome evolution that links chromosome number changes with karyotype morphology. Using our model, we infer that rates of chromosome number evolution are significantly lower in species with karyotypes that consist of either all bibrachial or all monobrachial chromosomes than in species with a mix of both types of morphologies. We suggest that species with homogeneous karyotypes may represent cases where meiotic drive acts to stabilize the karyotype, favoring the chromosome morphologies already present in the genome. In contrast, rapid bouts of chromosome number evolution in taxa with mixed karyotypes may indicate that a switch in the polarity of female meiotic drive favors changes in chromosome number. We do not find any evidence that karyotype morphology affects rates of speciation or extinction. Furthermore, we document that switches in meiotic drive polarity are likely common and have occurred in most major clades of mammals, and that rapid remodeling of karyotypes may be more common than once thought.
Genome-wide transcriptome profiling reveals genes associated with meiotic drive system of Aedes aegypti
3943Shin, DB, K. Susanta; Severson, W. David, Insects, 10:e25. 2019-01-21 00:00:00.
Aedes aegypti is an important mosquito vector of several arboviruses, including dengue, yellow fever, Zika, and Chikungunya, which cause significant human morbidity and mortality globally. In certain populations of this mosquito, a native meiotic drive system causes abnormal spermatogenesis that results in highly male-biased progenies from some matings. Although the basic genetics and cytogenetics of the drive mechanism were elucidated, very little is known on a transcriptome level about how the meiotic drive phenotype is expressed in individual males. To address this question, we conducted a whole-genome microarray expression study of testes from a meiotic-drive-carrying strain (T37) in comparison with testes from a non-drive-carrying strain (RED). Based on bioinformatics analyses of the microarray data, we identified 209 genes associated with the meiotic drive phenotype that were significantly differentially expressed between the two strains. K-means cluster analysis revealed nine clusters, in which genes upregulated in T37 testes were assigned to five clusters and genes downregulated in T37 testes were assigned to four clusters. Our data further revealed that genes related to protein translation, phosphorylation, and binding, as well as to G-protein-coupled receptor (GPCR) and peptidase activities, are differentially upregulated in testes from males with the meiotic drive genotype. Based on pathway analysis of these differentially expressed genes, it was observed that the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway may play a role in the meiotic drive system. Overall, this investigation enhances our understanding of whole-genome gene expression associated with the meiotic drive system in Ae. aegypti.
Transmission ratio distortion is frequent in Arabidopsis thaliana controlled crosses
3942Seymour, DKC, E.; Arioz, B. I.; Koenig, D.; Weigel, D., Heredity, 122:294-304. 2019-01-20 00:00:00.
The equal probability of transmission of alleles from either parent during sexual reproduction is a central tenet of genetics and evolutionary biology. Yet, there are many cases where this rule is violated. The preferential transmission of alleles or genotypes is termed transmission ratio distortion (TRD). Examples of TRD have been identified in many species, implying that they are universal, but the resolution of species-wide studies of TRD are limited. We have performed a species-wide screen for TRD in over 500 segregating F-2 populations of Arabidopsis thaliana using pooled reduced-representation genome sequencing. TRD was evident in up to a quarter of surveyed populations. Most populations exhibited distortion at only one genomic region, with some regions being repeatedly affected in multiple populations. Our results begin to elucidate the species-level architecture of biased transmission of genetic material in A. thaliana, and serve as a springboard for future studies into the biological basis of TRD in this species.
The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications
3889Beckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019-01-07 00:00:00.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin–antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Gene conversion generates evolutionary novelty that fuels genetic conflicts
3905Daugherty, MDZ, Sarah E., Current Opinion in Genetics & Development, 58-59:49-54. 2019-01-03 00:00:00.
Genetic conflicts arise when the evolutionary interests of two genetic elements are not aligned. Conflicts between genomes (e.g. pathogen versus host) or within the same genome (e.g. internal parasitic DNA sequences versus the rest of the host genome) can both foster ‘molecular arms races’, in which genes on both sides of the conflict rapidly evolve due to bouts of adaptation and counter-adaptation. Importantly, a source of genetic novelty is needed to fuel these arms races. In this review, we highlight gene conversion as a major force in generating the novel alleles on which selection can act. Using examples from both intergenomic and intragenomic conflicts, we feature the mechanisms by which gene conversion facilitates the rapid evolution of genes in conflict.
Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in Drosophila
3944Shropshire, JDB, S. R., PLOS Genetics, 15:e1008221. 2019-01-02 00:00:00.
Wolbachia are maternally inherited bacteria that infect arthropod species worldwide and are deployed in vector control to curb arboviral spread using cytoplasmic incompatibility (CI). CI kills embryos when an infected male mates with an uninfected female, but the lethality is rescued if the female and her embryos are likewise infected. Two phage WO genes, cifA(wMel) and cifB(wMel) from the wMel Wolbachia deployed in vector control, transgenically recapitulate variably penetrant CI, and one of the same genes, cifA(wMel), rescues wild type CI. The proposed Two-by-One genetic model predicts that CI and rescue can be recapitulated by transgenic expression alone and that dual cifA(wMel) and cifB(wMel) expression can recapitulate strong CI. Here, we use hatch rate and gene expression analyses in transgenic Drosophila melanogaster to demonstrate that CI and rescue can be synthetically recapitulated in full, and strong, transgenic CI comparable to wild type CI is achievable. These data explicitly validate the Two-by-One model in wMel-infected D. melanogaster, establish a robust system for transgenic studies of CI in a model system, and represent the first case of completely engineering male and female animal reproduction to depend upon bacteriophage gene products. Author summary Releases of Wolbachia-infected mosquitos are underway worldwide because Wolbachia block replication of Zika and Dengue viruses and spread themselves maternally through arthropod populations via cytoplasmic incompatibility (CI). The CI drive system depends on a Wolbachia-induced sperm modification that results in embryonic lethality when an infected male mates with an uninfected female, but this lethality is rescued when the female and her embryos are likewise infected. We recently reported that the phage WO genes, cifA and cifB, cause the sperm modification and cifA rescues the embryonic lethality caused by the wMel Wolbachia strain deployed in vector control. These reports motivated proposal of the Two-by-One model of CI whereby two genes cause lethality and one gene rescues it. Here we provide unequivocal support for the model in the Wolbachia strain used in vector control via synthetic methods that recapitulate CI and rescue in the absence of a Wolbachia infections. Our results reveal the set of phage WO genes responsible for this powerful genetic drive system, act as a proof-of-concept that these genes alone can induce gene drive like crossing patterns, and establish methodologies and hypotheses for future studies of CI in Drosophila. We discuss the implications of the Two-by-One model towards functional mechanisms of CI, the emergence of incompatibility between Wolbachia strains, vector control applications, and CI gene nomenclature.
Developing gene drive technologies to eradicate invasive rodents from islands
13798C. M. Leitschuh, D. Kanavy, G. A. Backus, R. X. Valdez, M. Serr, E. A. Pitts, D. Threadgill and J. Godwin, Journal of Responsible Innovation, 5:S121-S138. 2018-01-24 15:45:57.
Gene drive methods of rodent eradication offer an alternative to killing that has the potential to be more species-specific, more humane, and more biologically safe for use around humans. Implementing this technology would involve releasing laboratory-developed engineered mice into wild populations. Some areas for further research include assessing the ecological effects of releasing engineered mice, the potential risks for the accidental or deliberate release of genetically modified organisms into mainland mouse populations, and the social, ethical, and regulatory acceptability of the technology.
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
3980Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M., Journal of Responsible Innovation, 5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.
Genetic villains: Killer meiotic drivers
3959Bravo Núñez, MAN, Nicole L.; Zanders, Sarah E., Trends in Genetics, 34:424-433. 2018-01-17 00:00:00.
Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.
Rapid comeback of males: evolution of male-killer suppression in a green lacewing population
3979Hayashi, MN, M.; Kageyama, D., Proceedings of the Royal Society B-Biological Sciences, 285:6. 2018-01-17 00:00:00.
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi. An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
Selfish genetic elements
3955Agren, JAC, A. G., PLOS Genetics, 14:20. 2018-01-13 00:00:00.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12]
Gene flow mediates the role of sex chromosome meiotic drive during complex speciation
3994Meiklejohn, CDL, Emily L.; Gordon, Kathleen E.; Rzatkiewicz, Thomas; Kingan, Sarah B.; Geneva, Anthony J.; Vedanayagam, Jeffrey P.; Muirhead, Christina A.; Garrigan, Daniel; Stern, David L.; Presgraves, Daven C., eLife, 7:e35468. 2018-01-12 00:00:00.
During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.
Gene drive: Evolved and synthetic
3964Burt, AC, Andrea, ACS Chemical Biology, 13:343-346. 2018-01-02 00:00:00.
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to—or indeed even if they detract from—organismal survival and reproduction. Genetic elements that can spread by drive include gametic and zygotic killers, meiotic drivers, homing endonuclease genes, B chromosomes, and transposable elements. The fact that gene drive can lead to the spread of fitness-reducing traits (including lethality and sterility) makes it an attractive process to consider exploiting to control disease vectors and other pests. There are a number of efforts to develop synthetic gene drive systems, particularly focused on the mosquito-borne diseases that continue to plague us.
Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly
4024Verspoor Rudi, LSJ, M. L.; Mannion Natasha, L. M.; Hurst Gregory, D. D.; Price Tom, A. R., Evolution Letters, 2:169-179. 2018-01-02 00:00:00.
Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics remain poorly understood. Simple population genetic models predict meiotic drivers will rapidly reach fixation in populations and spread across landscapes. In contrast, natural populations commonly show spatial variation in the frequency of drivers, with drive present in clines or mosaics across species ranges. For example, Drosophila subobscura harbors a sex ratio distorting drive chromosome (SRs) at 15?25% frequency in North Africa, present at less than 2% frequency in adjacent southern Spain, and absent in other European populations. Here, we investigate the forces preventing the spread of the driver northward. We show that SRs has remained at a constant frequency in North Africa, and failed to spread in Spain. We find strong evidence that spread is impeded by genetic incompatibility between SRs and Spanish autosomal backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds we observe strong incompatibilities specific to hybrids bearing SRs. The incompatibilities increase in severity in F2 male hybrids, leading to almost complete infertility. We find no evidence supporting an alternative hypothesis, that there is resistance to drive in Spanish populations. We conclude that the source of the stepped frequency variation is genetic incompatibility between the SRs chromosome and the genetic backgrounds of the adjacent population, preventing SRs spreading northward. The low frequency of SRs in South Spain is consistent with recurrent gene flow across the Strait of Gibraltar combined with selection against the SRs element through genetic incompatibility. This demonstrates that incompatibilities between drive chromosomes and naïve populations can prevent the spread of drive between populations, at a continental scale.
How selfish DNA hijacks its way into egg cells
13516Science, 2017-11-06 13:52:33.
This video was produced by Science magazine and explains and illustrates how gonotaxis or the asymmetrical allocation of chromosomes to developing female gametes occurs in mice. This video reflects an understanding of this process based on the publication by Akera et al (2017).
Spindle asymmetry drives non-Mendelian chromosome segregation
13518T. Akera, L. Chmátal, E. Trimm, K. Yang, C. Aonbangkhen, D. M. Chenoweth, C. Janke, R. M. Schultz and M. A. Lampson, Science, 358:668. 2017-11-03 14:19:19.
Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through a process known as meiotic drive. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle. This implies some asymmetry between the two sides of the spindle, but the molecular mechanisms underlying spindle asymmetry are unknown. Here we found that CDC42 signaling from the cell cortex regulated microtubule tyrosination to induce spindle asymmetry and that non-Mendelian segregation depended on this asymmetry. Cortical CDC42 depends on polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.
A maternal-effect selfish genetic element in Caenorhabditis elegans
14450E. Ben-David, A. Burga and L. Kruglyak, Science, 356:1051. 2017-06-09 17:13:17.
We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans.
Poisons, antidotes, and selfish genes
14448N. Phadnis, Science, 356:1013. 2017-06-09 16:55:51.
On page1051 of this issue, BenDavid et al . (3) chase down a serendipitous observation of an anomaly in genetic crosses to unmask a toxin-antidote type of selfish system in worms.
wtf genes are prolific dual poison-antidote meiotic drivers
4060Nuckolls, NLN, M. A. B.; Eickbush, M. T.; Young, J. M.; Lange, J. J.; Yu, J. S.; Smith, G. R.; Jaspersen, S. L.; Malik, H. S.; Zanders, S. E., eLife, 6:e26033. 2017-01-18 00:00:00.
Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility.
Genetic conflicts: the usual suspects and beyond
4058McLaughlin, RNM, H. S., Journal of Experimental Biology, 220:6-17. 2017-01-16 00:00:00.
Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements.
Gene drives do not always increase in frequency: from genetic models to risk assessment
4036de Jong, TJ, Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety, 12:299-307. 2017-01-14 00:00:00.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an overrepresentation of the homing allele in the next generation. GD may propel CRISPR-Cas9 genes and new genes physically coupled to the GD through natural populations. I revisit the population genetic models of GD with the aim of making these models more understandable to non-specialists. What can we learn about risk evaluation from the models? A GD with no or a small effect on fitness (viability) always spreads in the population and goes to fixation. That is provided that no resistance mechanism evolves, for instance due to a mutation in the target site. However, when GDs have a large negative effect on fitness, their spread depends on a threshold or they may not spread at all. The chance of GDs increasing until fixation is much higher in systems with meiotic drive than in systems with embryo conversion. The presence or absence of a meiotic promoter is therefore relevant to take into account in the environmental risk assessment.
Sperm competition suppresses gene drive among experimentally evolving populations of house mice
4056Manser, AL, A. K.; Simmons, L. W.; Firman, R. C., Molecular Ecology, 26:5784-5792. 2017-01-14 00:00:00.
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive-carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.
The promise and peril of CRISPR gene drives
4076Zentner, GEW, Michael J. C., Bioessays, 39:1-9. 2017-01-14 00:00:00.
Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.
A pooled sequencing approach identifies a candidate meiotic driver in Drosophila
4072Wei, KHCR, H. M.; Rathnam, C.; Lee, J.; Lin, D. A. N.; Ji, S. Q.; Mason, J. M.; Clark, A. G.; Barbash, D. A., Genetics, 206:451-465. 2017-01-10 00:00:00.
Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here, we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide with single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an similar to 8% increase in transmission frequency, corresponding to a similar to 54: 46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of BC1 progeny.
Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
4044Gonen, SJ, J.; Gorjanc, G.; Mileham, A. J.; Whitelaw, C. B. A.; Hickey, J. M., Genetics Selection Evolution, 49:14. 2017-01-02 00:00:00.
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods: We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance (sigma(2)(A)), rate of change in inbreeding (Delta F), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Results: Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Conclusions: Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding.
No evidence for female discrimination against male house mice carrying a selfish genetic element
4103Sutter, AL, A. K., Current Zoology, 62:675-685. 2016-01-21 00:00:00.
Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/t) mice leads to high embryo mortality. Previous experiments showing that +/t females avoid this incompatibility cost by preferring +/+versus +/t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.
Random and non-random mating populations: Evolutionary dynamics in meiotic drive
4101Sarkar, B, Mathematical Biosciences, 271:29-41. 2016-01-19 00:00:00.
Game theoretic tools are utilized to analyze a one-locus continuous selection model of sex-specific meiotic drive by considering nonequivalence of the viabilities of reciprocal heterozygotes that might be noticed at an imprinted locus. The model draws attention to the role of viability selections of different types to examine the stable nature of polymorphic equilibrium. A bridge between population genetics and evolutionary game theory has been built up by applying the concept of the Fundamental Theorem of Natural Selection. In addition to pointing out the influences of male and female segregation ratios on selection, configuration structure reveals some noted results, e.g., Hardy-Weinberg frequencies hold in replicator dynamics, occurrence of faster evolution at the maximized variance fitness, existence of mixed Evolutionarily Stable Strategy (ESS) in asymmetric games, the tending evolution to follow not only a 1:1 sex ratio but also a 1:1 different alleles ratio at particular gene locus. Through construction of replicator dynamics in the group selection framework, our selection model introduces a redefining bases of game theory to incorporate non-random mating where a mating parameter associated with population structure is dependent on the social structure. Also, the model exposes the fact that the number of polymorphic equilibria will depend on the algebraic expression of population structure. (C) 2015 Elsevier Inc. All rights reserved.
Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome
4100Rydzewski, WTC, S. A.; Lievano, G.; Lynch, V. D.; Patten, M. M., Journal of Evolutionary Biology, 29:1247-1256. 2016-01-18 00:00:00.
Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, D-z('), which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome.
Intragenomic conflict produces sex ratio dynamics that favor maternal sex ratio distorters
4099Rood, ESF, S., Ecology and Evolution, 6:8085-8093. 2016-01-17 00:00:00.
Maternal sex ratio distorters (MSDs) are selfish elements that enhance their transmission by biasing their host's sex allocation in favor of females. While previous models have predicted that the female-biased populations resulting from sex ratio distortion can benefit from enhanced productivity, these models neglect Fisherian selection for nuclear suppressors, an unrealistic assumption in most systems. We used individual-based computer simulation modeling to explore the intragenomic conflict between sex ratio distorters and their suppressors and explored the impacts of these dynamics on population-level competition between species characterized by MSDs and those lacking them. The conflict between distorters and suppressors was capable of producing large cyclical fluctuations in the population sex ratio and reproductive rate. Despite fitness costs associated with the distorters and suppressors, MSD populations often exhibited enhanced productivity and outcompeted non-MSD populations in single and multiple-population competition simulations. Notably, the conflict itself is beneficial to the success of populations, as sex ratio oscillations limit the competitive deficits associated with prolonged periods of male rarity. Although intragenomic conflict has been historically viewed as deleterious to populations, our results suggest that distorter-suppressor conflict can provide population-level advantages, potentially helping to explain the persistence of sex ratio distorters in a range of taxa.
A meiotic drive element in the maize pathogen Fusarium verticillioides is located within a 102 kb region of chromosome V
4098Pyle, JP, T.; Merrill, B.; Nsokoshi, C.; McCall, M.; Proctor, R. H.; Brown, D. W.; Hammond, T. M., G3-Genes Genomes Genetics, 6:2543-2552. 2016-01-16 00:00:00.
Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) x Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) x Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1. The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.
Comparative analysis of regions with distorted segregation in three diploid populations of potato
4094Manrique-Carpintero, NCC, J. J.; Veilleux, R. E.; Buell, C. R.; Douches, D. S., G3-Genes Genomes Genetics, 6:2617-2628. 2016-01-12 00:00:00.
Genes associated with gametic and zygotic selection could underlie segregation distortion, observed as alterations of expected Mendelian genotypic frequencies in mapping populations. We studied highly dense genetic maps based on single nucleotide polymorphisms to elucidate the genetic nature of distorted segregation in potato. Three intra-and interspecific diploid segregating populations were used. DRH and D84 are crosses between the sequenced doubled monoploid DM 1-3 516 R44 Solanum tuberosum Group Phureja and either RH89-039-16 S. tuberosum or 84SD22, a S. tuberosum x S. chacoense hybrid. MSX902 is an interspecific cross between 84SD22 and Ber83 S. berthaultii x 2 x species mosaic. At the 0.05 significance level, 21%, 57%, and 51% of the total markers mapped in DRH, D84, and MSX902 exhibited distorted segregation, respectively. Segregation distortion regions for DRH were located on chromosomes 9 and 12; for D84 on chromosomes 2, 3, 4, 6, 7, and 8; and on chromosomes 1, 2, 7, 9, and 12 for MSX902. In general, each population had unique segregation distortion regions and directions of distortion. Interspecific crosses showed greater levels of distorted segregation and lower recombination rates as determined from the male parents. The different genomic regions where the segregation distortion regions occurred in the three populations likely reflect unique genetic combinations producing distorted segregation.
The Ecology and Evolutionary Dynamics of Meiotic Drive
4092Lindholm, AKD, K. A.; Firman, R. C.; Fishman, L.; Forstmeier, W.; Holman, L.; Johannesson, H.; Knief, U.; Kokko, H.; Larracuente, A. M.; Manser, A.; Montchamp-Moreau, C.; Petrosyan, V. G.; Pomiankowski, A.; Presgraves, D. C.; Safronova, L. D.; Sutter, A.; Unckless, R. L.; Verspoor, R. L.; Wedell, N.; Wilkinson, G. S.; Price, T. A. R., Trends in Ecology & Evolution, 31:315-326. 2016-01-10 00:00:00.
Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.
Rapid evolution of a Y-chromosome heterochromatin protein underlies sex chromosome meiotic drive
4088Helleu, QG, P. R.; Dubruille, R.; Ogereau, D.; Prud'homme, B.; Loppin, B.; Montchamp-Moreau, C., Proceedings of the National Academy of Sciences of the United States of America, 113:4110-4115. 2016-01-06 00:00:00.
Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans. Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.
The ability to gain matings, not sperm competition, reduces the success of males carrying a selfish genetic element in a fly
4105Verspoor, RLH, G. D. D.; Price, T. A. R., Animal Behaviour, 115:207-215. 2016-01-03 00:00:00.
Females are expected to avoid low-quality males fathering their offspring. X chromosome meiotic drive (XCMD) makes males very low-quality mates. XCMDs are X chromosomes that, in males, cause the failure of all Y chromosome sperm, so all functional sperm carry the driving X and produce daughters. This transmission advantage can allow the XCMD to spread through populations. However, XCMD males typically have low fertility, are very poor at sperm competition, only produce daughters, and bear low fitness alleles associated with XCMD. This imposes significant costs on females that mate with these males. Recently, several studies have shown that females can reduce the risk of their offspring inheriting XCMDs by mating with multiple males (polyandry), as XCMD males typically lose out to normal males in sperm competition. Hence it has been suggested that increased polyandry may be likely to evolve whenever a costly XCMD is common in a population, and that polyandry may be a key factor in preventing XCMDs spreading through populations. We tested this by examining the fruit fly Drosophila subobscura, in which females are known to mate only once in European populations where XCMDs are absent. However, in North African populations an XCMD, referred to as 'SRs', occurs. If the association between XCMDs and polyandry is true, then these North African populations should have evolved polyandry. However, we found no evidence of polyandry in North African D. subobscura populations. Instead, we found some evidence that males that carry SRs are slightly less successful at gaining matings in noncompetitive situations. These results show that polyandry does not necessarily evolve in response to the presence of harmful X chromosome drive. With both sperm competition and female choice both being unlikely to substantially reduce the success of XCMD in D. subobscura, the factors that prevent SRs spreading through these populations remain mysterious. (C) 2016 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.
The dawn of active genetics
4085Gantz, VMB, E., Bioessays, 38:50-63. 2016-01-03 00:00:00.
On December 18, 2014, a yellow female fly quietly emerged from her pupal case. What made her unique was that she had only one parent carrying a mutant allele of this classic recessive locus. Then, one generation later, after mating with a wild-type male, all her offspring displayed the same recessive yellow phenotype. Further analysis of other such yellow females revealed that the construct causing the mutation was converting the opposing chromosome with 95% efficiency. These simple results, seen also in mosquitoes and yeast, open the door to a new era of genetics wherein the laws of traditional Mendelian inheritance can be bypassed for a broad variety of purposes. Here, we consider the implications of this fundamentally new form of active genetics, its applications for gene drives, reversal and amplification strategies, its potential for contributing to cell and gene therapy strategies, and ethical/biosafety considerations associated with such active genetic elements.
Meiotic drive changes sperm precedence patterns in house mice: potential for male alternative mating tactics?
4104Sutter, AL, A. K., BMC Evolutionary Biology, 16:15. 2016-01-02 00:00:00.
Background: With female multiple mating (polyandry), male-male competition extends to after copulation (sperm competition). Males respond to this selective pressure through physiological, morphological and behavioural adaptations. Sperm competitiveness is commonly decreased in heterozygote carriers of male meiotic drivers, selfish genetic elements that manipulate the production of gametes in males. This might give carriers an evolutionary incentive to reduce the risk of sperm competition. Here, we explore this possibility in house mice. Natural populations frequently harbour a well-characterised male driver (t haplotype), which is transmitted to 90 % of heterozygous (+/t) males' offspring. Previous research demonstrated strong detrimental effects on sperm competitiveness, and suggested that +/t males are particularly disadvantaged against wild type males when first-to-mate. Low paternity success in the first-to-mate role is expected to favour male adaptations that decrease the risk of sperm competition by preventing female remating. Genotype-specific paternity patterns (sperm precedence) could lead to genetically determined alternative reproductive tactics that can spread through gene level selection. Here, we seek confirmation that +/t males are generally disadvantaged when first-to-mate and address whether males of different genotypes differ in reproductive tactics (copulatory and morphological) to maximise individual or driver fitness. Finally, we attempt to explain the mechanistic basis for alternative sperm precedence patterns in this species. Results: We confirmed that +/t males are weak sperm competitors when first to mate. When two +/t males competed, the second-to-mate was more successful, which contrasts with first male sperm precedence when wild type males competed. However, we found no differences between male genotypes in reproductive behaviour or morphology that were consistent with alternative reproductive tactics. Sperm of +/+ and +/t males differed with respect to in vitro sperm features. Premature hypermotility in +/t males' sperm can potentially explain why +/t males are very weak sperm competitors when first-to-mate. Conclusions: Our results demonstrate that meiotic drivers can have strong effects on sperm precedence patterns, and may provide a heritable basis for alternative reproductive tactics motivated by reduced sperm competitiveness. We discuss how experimental and evolutionary constraints may help explain why male genotypes did not show the predicted differences.
R2d2 drives selfish sweeps in the house mouse
4084Didion, JPM, A. P.; Yadgary, L.; Bell, T. A.; McMullan, R. C.; de Solorzano, L. O.; Britton-Davidian, J.; Bult, C. J.; Campbell, K. J.; Castiglia, R.; Ching, Y. H.; Chunco, A. J.; Crowley, J. J.; Chesler, E. J.; Forster, D. W.; French, J. E.; Gabriel, S. I.; Gatti, D. M.; Garland, T.; Giagia-Athanasopoulou, E. B.; Gimenez, M. D.; Grize, S. A.; Gunduz, I.; Holmes, A.; Hauffe, H. C.; Herman, J. S.; Holt, J. M.; Hua, K. J.; Jolley, W. J.; Lindholm, A. K.; Lopez-Fuster, M. J.; Mitsainas, G.; Mathias, M. D.; McMillan, L.; Ramalhinho, M. D. M.; Rehermann, B.; Rosshart, S. P.; Searle, J. B.; Shiao, M. S.; Solano, E.; Svenson, K. L.; Thomas-Laemont, P.; Threadgill, D. W.; Ventura, J.; Weinstock, G. M.; Pomp, D.; Churchill, G. A.; de Villena, F. P. M., Molecular Biology and Evolution, 33:1381-1395. 2016-01-02 00:00:00.
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
Double trouble: combined action of meiotic drive and Wolbachia feminization in Eurema butterflies
4119Kern, PC, J. M.; Kageyama, D.; Riegler, M., Biology Letters, 11:20150095. 2015-01-17 00:00:00.
Arthropod sex ratios can be manipulated by a diverse range of selfish genetic elements, including maternally inherited Wolbachia bacteria. Feminization by Wolbachia is rare but has been described for Eurema mandarina butterflies. In this species, some phenotypic and functional females, thought to be ZZ genetic males, are infected with a feminizing Wolbachia strain, wFem. Meanwhile, heterogametic WZ females are not infected with wFem. Here, we establish a quantitative PCR assay allowing reliable sexing in three Eurema species. Against expectation, all E. mandarina females, including wFem females, had only one Z chromosome that was paternally inherited. Observation of somatic interphase nuclei confirmed that W chromatin was absent in wFem females, but present in females without wFem. We conclude that the sex bias in wFem lines is due to meiotic drive (MD) that excludes the maternal Z and thus prevents formation of ZZ males. Furthermore, wFem lines may have lost the W chromosome or harbour a dysfunctional version, yet rely on wFem for female development; removal of wFem results in all-male offspring. This is the first study that demonstrates an interaction between MD and Wolbachia feminization, and it highlights endosymbionts as potentially confounding factors in MD of sex chromosomes.
Sex chromosome drive
4117Helleu, QG, P. R.; Montchamp-Moreau, C., Cold Spring Harbor Perspectives in Biology, 7:a017616. 2015-01-15 00:00:00.
Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are over represented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.
Mating type and spore killing characterization of Fusarium verticillioides strains
4116Guo, LB, A. Z.; Geiser, D. M.; Jimenez-Gasco, M. D.; Kuldau, G. A., Mycological Progress, 14:1045. 2015-01-14 00:00:00.
Fusarium verticillioides is a heterothallic ascomycete causing maize ear rot, and produces fumonisin mycotoxins harmful to livestock and human health. A meiotic drive phenomenon called spore killing has been reported in several filamentous fungi including F. verticillioides. F. verticillioides reference genome strain M-3125 (FGSC 7600) is spore killer sensitive (SKS), and genetic crosses of M-3125 with a strain carrying SKK (the killer element) result in only four viable ascospores per ascus instead of the normal eight ascospores. We sought to identify a strain of F. verticillioides that is SKS and MAT1-2 for use in genetic analysis with M-3125. To accomplish this, we screened 50 F. verticillioides strains from the Fusarium Research Center at The Pennsylvania State University, USA for spore killing. To characterize the mating types of these strains, portions of the MAT locus idiomorphs were amplified using polymerase chain reaction, and genetic crosses were performed. The PCR amplification results show that 18 of the 50 strains are MAT1-2 and 32 are MAT1-1. Genetic crosses between M-3125 and 11 of the 18 MAT1-2 strains produced normal perithecia. Crosses between two (M-8024 and M-7815) of the 11 strains and M-3125 produced perithecia with eight ascospores per ascus, and nine others had only four ascospores per ascus, suggesting that M-8024 and M-7815 are SKS and the other nine are SKK. This study expands our knowledge of mating type and spore killing in F. verticillioides and identifies two SKS, MAT1-2 strains for use in genetic crosses with genome reference strain M-3125.
Centromere-associated meiotic drive and female fitness variation in Mimulus
4113Fishman, LK, J. K., Evolution, 69:1208-1218. 2015-01-11 00:00:00.
Female meiotic drive, in which chromosomal variants preferentially segregate to the egg pole during asymmetric female meiosis, is a theoretically pervasive but still mysterious form of selfish evolution. Like other selfish genetic elements, driving chromosomes may be maintained as balanced polymorphisms by pleiotropic or linked fitness costs. A centromere-associated driver (D) with a approximate to 58:42 female-specific transmission advantage occurs at intermediate frequency (32-40%) in the Iron Mountain population of the yellow monkeyflower, Mimulus guttatus. Previously determined male fertility costs are sufficient to prevent the fixation of D, but predict a higher equilibrium frequency. To better understand the dynamics and effects of D, we developed a new population genetic model and measured genotype-specific lifetime female fitness in the wild. In three of four years, and across all years, D imposed significant recessive seedset costs, most likely due to hitchhiking by deleterious mutations. With both male and female costs as measured, and 58:42 drive, our model predicts an equilibrium frequency of D (38%) very close to the observed value. Thus, D represents a rare selfish genetic element whose local population genetic dynamics have been fully parameterized, and the observation of equilibrium sets the stage for investigations of coevolution with suppressors.
Duplication and adaptive evolution of a key centromeric protein in Mimulus, a genus with female meiotic drive
4112Finseth, FRD, Y. Z.; Saunders, A.; Fishman, L., Molecular Biology and Evolution, 32:2694-2706. 2015-01-10 00:00:00.
The fundamental asymmetry of female meiosis creates an arena for genetic elements to compete for inclusion in the egg, promoting the selfish evolution of centromere variants that maximize their transmission to the future egg. Such "female meiotic drive" has been hypothesized to explain the paradoxically complex and rapidly evolving nature of centromeric DNA and proteins. Although theoretically widespread, few cases of active drive have been observed, thereby limiting the opportunities to directly assess the impact of centromeric drive on molecular variation at centromeres and binding proteins. Here, we characterize the molecular evolutionary patterns of CENH3, the centromere-defining histone variant, in Mimulus monkeyflowers, a genus with one of the few known cases of active centromere-associated female meiotic drive. First, we identify a novel duplication of CENH3 in diploid Mimulus, including in lineages with actively driving centromeres. Second, we demonstrate long-term adaptive evolution at several sites in the N-terminus of CENH3, a region with some meiosis-specific functions that putatively interacts with centromeric DNA. Finally, we infer that the paralogs evolve under different selective regimes; some sites in the N-terminus evolve under positive selection in the pro-orthologs or only one paralog (CENH3_B) and the paralogs exhibit significantly different patterns of polymorphism within populations. Our finding of long-term, adaptive evolution at CENH3 in the context of centromere-associated meiotic drive supports an antagonistic, coevolutionary battle for evolutionary dominance between centromeric DNA and binding proteins.
R2d2 and hyperdrive mechanisms (in Mouse meiosis)
4132Zanders, SEM, H. S., PLOS Genetics, 11:1-4. 2015-01-10 00:00:00.
Mendelian transmission is established during meiosis, the cell division that generates haploidgametes (e.g., sperm and eggs) from diploid germ cells. Meiosis does not, however, have to befair. Selfish genetic elements, or meiotic drivers, have evolved to cheat this process in order tobe packaged into functional gametes more often than the expected 50% probability. By biasingallele transmission in their favor, meiotic drive alleles can short-circuit natural selection, caus-ing their spread even if they are harmful to organismal fitness. Indeed, meiotic drive alleles arethought to be directly or indirectly associated with infertility in diverse eukaryotes, from fungito flies to humans [2].
Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster
4108Brand, CLL, A. M.; Presgraves, D. C., Evolution, 69:1271-1283. 2015-01-06 00:00:00.
Meiotic drive elements are a special class of evolutionarily selfish genes that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
Sex-ratio meiotic drive and Y-linked resistance in Drosophila affinis
4128Unckless, RLL, A. M.; Clark, A. G., Genetics, 199:831-840. 2015-01-06 00:00:00.
Genetic elements that cheat Mendelian segregation by biasing transmission in their favor gain a significant fitness benefit. Several examples of sex-ratio meiotic drive, where one sex chromosome biases its own transmission at the cost of the opposite sex chromosome, exist in animals and plants. While the distorting sex chromosome gains a significant advantage by biasing sex ratio, the autosomes, and especially the opposite sex chromosome, experience strong selection to resist this transmission bias. In most wellstudied sex-ratio meiotic drive systems, autosomal and/or Y-linked resistance has been identified. We specifically surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis by scoring the sex ratio of offspring sired by males with a driving X and one of several Y chromosomes. Two distinct types of resistance were identified: a restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons. We confirmed that fathers siring all sons lacked a Y chromosome, consistent with previously published work. Considerable variation in Y-chromosome morphology exists in D. affinis, but we showed that morphology does not appear to be associated with resistance to sex-ratio meiotic drive. We then used two X chromosomes (driving and standard) and three Y chromosomes (susceptible, resistant, and lacking) to examine fertility effects of all possible combinations. We find that both the driving X and resistant and lacking Y have significant fertility defects manifested in microscopic examination of testes and a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic drive system, including both the X-linked distorter and the Y-resistant effects, appear to be mediated by a complex interaction between fertility fitness and transmission dynamics.
Detrimental effects of an autosomal selfish genetic element on sperm competitiveness in house mice
4126Sutter, AL, A. K., Proceedings of the Royal Society B-Biological Sciences, 282:1-8. 2015-01-04 00:00:00.
Female multiple mating (polyandry) is widespread across many animal taxa and indirect genetic benefits are a major evolutionary force favouring polyandry. An incentive for polyandry arises when multiple mating leads to sperm competition that disadvantages sperm from genetically inferior mates. A reduction in genetic quality is associated with costly selfish genetic elements (SGEs), and studies in invertebrates have shown that males bearing sex ratio distorting SGEs are worse sperm competitors than wild-type males. We used a vertebrate model species to test whether females can avoid an autosomal SGE, the t haplotype, through polyandry. The t haplotype in house mice exhibits strong drive in t heterozygous males by affecting spermatogenesis and is associated with homozygous in utero lethality. We used controlled matings to test the effect of the t haplotype on sperm competitiveness. Regardless of mating order, t heterozygous males sired only 11% of zygotes when competing against wild-type males, suggesting a very strong effect of the t haplotype on sperm quality. We provide, to our knowledge, the first substantial evidence that polyandry ameliorates the harmful effects of an autosomal SGE arising through genetic incompatibility. We discuss potential mechanisms in our study species and the broader implications for the benefits of polyandry.
Presence of segregation distortion in sheep
4125Raed, MA, Research Journal of Biotechnology, 10:87-98. 2015-01-03 00:00:00.
The main objective of this project was the investigation of presence of segregation distortion (SD) and description of other relevant parameters of multilocus genetics in Australian Merino sheep. The SD cases investigated three flocks of 98, 79 and 92 offspring and their DNA-based identified dams and sires. DNA samples were genotyped for 28 microsatellite (MS) markers located on different chromosomes. SD was estimated by studying the paternal segregation of alleles in offspring using a bootstrap procedure. The results showed a high proportion of studied loci which demonstrated significant SD. The results provided additional data which add to the common knowledge that sheep population structure and dynamics are affected by evolutionary forces such as gene flow, selection and many other random factors. These forces were noticed in the three populations. Finally, the results obtained from many loci in this project provided evidence of Mendelian violation. Moreover, they indicated that genes affecting male-related SD are spread over the genome.
Genetic Control of Mosquitoes.
5597Alphey, L., Annual Review of Entomology, 59:205-224. 2014-12-17 15:50:24.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
A critical component of meiotic drive in Neurospora is located near a chromosome rearrangement
4143Harvey, AMR, D. G.; Groskreutz, K. M.; Kuntz, D. R.; Sharp, K. J.; Shiu, P. K. T.; Hammond, T. M., Genetics, 197:1165-1179. 2014-01-21 00:00:00.
Neurospora fungi harbor a group of meiotic drive elements known as Spore killers (Sk). Spore killer-2 (Sk-2) and Spore killer-3 (Sk-3) are two Sk elements that map to a region of suppressed recombination. Although this recombination block is limited to crosses between Sk and Sk-sensitive (Sk(S)) strains, its existence has hindered Sk characterization. Here we report the circumvention of this obstacle by combining a classical genetic screen with next-generation sequencing technology and three-point crossing assays. This approach has allowed us to identify a novel locus called rfk-1, mutation of which disrupts spore killing by Sk-2. We have mapped rfk-1 to a 45-kb region near the right border of the Sk-2 element, a location that also harbors an 11-kb insertion (Sk-2(INS1)) and part of a >220-kb inversion (Sk-2(INV1)). These are the first two chromosome rearrangements to be formally identified in a Neurospora Sk element, providing evidence that they are at least partially responsible for Sk-based recombination suppression. Additionally, the proximity of these chromosome rearrangements to rfk-1 (a critical component of the spore-killing mechanism) suggests that they have played a key role in the evolution of meiotic drive in Neurospora.
Genes that bias Mendelian segregation
4142Grognet, PL, H.; Malagnac, F.; Silar, P., PLOS Genetics, 10:e1004387. 2014-01-20 00:00:00.
Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.
Genome rearrangements and pervasive meiotic drive cause hybrid infertility in fission yeast
4162Zanders, SEE, M. T.; Yu, J. S.; Kang, J. W.; Fowler, K. R.; Smith, G. R.; Malik, H. S., eLife, 3:e02630. 2014-01-20 00:00:00.
Hybrid sterility is one of the earliest postzygotic isolating mechanisms to evolve between two recently diverged species. Here we identify causes underlying hybrid infertility of two recently diverged fission yeast species Schizosaccharomyces pombe and S. kambucha, which mate to form viable hybrid diploids that efficiently complete meiosis, but generate few viable gametes. We find that chromosomal rearrangements and related recombination defects are major but not sole causes of hybrid infertility. At least three distinct meiotic drive alleles, one on each S. kambucha chromosome, independently contribute to hybrid infertility by causing nonrandom spore death. Two of these driving loci are linked by a chromosomal translocation and thus constitute a novel type of paired meiotic drive complex. Our study reveals how quickly multiple barriers to fertility can arise. In addition, it provides further support for models in which genetic conflicts, such as those caused by meiotic drive alleles, can drive speciation.
Segregation distortion affected by transgenes in early generations of rice crop-weed hybrid progeny: Implications for assessing potential evolutionary impacts from transgene flow into wild relatives
4161Yang, CW, Z.; Yang, X.; Lu, B. R., Journal of Systematics and Evolution, 52:466-476. 2014-01-19 00:00:00.
The significant role of segregation distortion as a driving force of evolution has increasingly gained recognition worldwide. Segregation distortion of parental alleles is commonly reported in hybrid progeny between crops and wild relative species, which possibly influences the evolution potential of the hybrid progeny. Whether transgene introgression into wild and weedy populations through repeated hybridization causes changes of segregation distortion of parental alleles in hybrid progeny is an important question to be addressed to understand the long-term evolution potential of the populations that have received transgenes. To study the influence of a transgene on allelic segregation, we examined gene and genotype frequencies in transgenic and non-transgenic populations of F-3 and F-4 lineages derived from hybrids between transgenic insect-resistant rice (Bt/CpTI) and weedy rice, involving randomly selected 25 simple sequence repeat markers with polymorphisms between the two parents. We found that the transgenes can significantly alter the segregation distortion pattern in hybrid progeny, particularly the direction of segregation deviated to different parents. In transgenic F-3 and F-4 populations, there are approximately 64% and 77% simple sequence repeat loci, respectively, with alleles deviated significantly to the insect-resistant cultivated rice parent; whereas, in non-transgenic F-3 and F-4 populations, approximately 68% and 58% loci, respectively, deviated significantly to the weedy rice parent. Transgenes with strong selection advantages may have evolutionary impacts on hybrid progeny by changing their pattern of allelic segregation distortion after introgression from transgenic crops to wild relatives through hybridization.
Male eyespan size is associated with meiotic drive in wild stalk-eyed flies (Teleopsis dalmanni)
4138Cotton, AJF, M.; Cotton, S.; Pomiankowski, A., Heredity, 112:363-369. 2014-01-16 00:00:00.
This study provides the first direct evidence from wild populations of stalk-eyed flies to support the hypothesis that male eyespan is a signal of meiotic drive. Several stalk-eyed fly species are known to exhibit X-linked meiotic drive. A recent quantitative trait locus analysis in Teleopsis dalmanni found a potential link between variation in male eyespan, a sexually selected ornamental trait, and the presence of meiotic drive. This was based on laboratory populations subject to artificial selection for male eyespan. In this study, we examined the association between microsatellite markers and levels of sex ratio bias (meiotic drive) in 12 wild T. dalmanni populations. We collected two data sets: (a) brood sex ratios of wild-caught males mated to standard laboratory females and (b) variation in a range of phenotypic traits associated with reproductive success of wild-caught males and females. In each case, we typed individuals for eight X-linked microsatellite markers, including several that previously were shown to be associated with male eyespan and meiotic drive. We found that one microsatellite marker was very strongly associated with meiotic drive, whereas a second showed a weaker association. We also found that, using both independent data sets, meiotic drive was strongly associated with male eyespan, with smaller eyespan males being associated with more female-biased broods. These results suggest that mate preference for exaggerated male eyespan allows females to avoid mating with males carrying the meiotic drive gene and is thus a potential mechanism for the maintenance and evolution of female mate preference.
Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice
4137Chmatal, LG, S. I.; Mitsainas, G. P.; Martinez-Vargas, J.; Ventura, J.; Searle, J. B.; Schultz, R. M.; Lampson, M. A., Current Biology, 24:2295-2300. 2014-01-15 00:00:00.
Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames [1-3]. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 102-10 s years [4, 5]. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric [5]. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel's first law [3, 6, 7]. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution.
An X-linked sex ratio distorter in Drosophila simulans that kills or incapacitates both noncarrier sperm and sons
4156Rice, WR, G3-Genes Genomes Genetics, 4:1837-1848. 2014-01-14 00:00:00.
Genomic conflict occurs when a genomic component gains a reproductive advantage at the expense of the organism as a whole. X-linked segregation distorters kill or incapacitate Y-bearing sperm, thereby gaining a transmission advantage but also reducing male fertility and generating a female-biased sex ratio. When some damaged, Y-bearing sperm survive and fertilize eggs, then the segregation distortion phenotype could be expanded by harming or killing sons in the next generation. X-linked son-killers are predicted by theory to be favored by natural selection and evolve when brothers and sisters compete for shared limiting resources and/or when brothers reduce the inclusive fitness of their sisters via sib-mating-a phenomenon called SA-zygotic drive. Here I develop and use a process-of-elimination screen to show that an unclassified X-linked sex ratio distorter (skew) in Drosophila simulans kills or incapacitates noncarrier sperm and also kills a substantial proportion of sons, i.e., it has both a segregation distortion and a SA-zygotic drive phenotype. There are three unique X-linked segregation distorters known to occur in D. simulans named Winters, Durham, and Paris. Autosomal-dominant suppressors of Winters (Nmy) and Durham (Tmy) failed to suppress skew. A Y-linked suppressor of Paris, however, did suppress skew, and a recombination test failed to detect recombinants between these two sex ratio distorters, indicating that they are tightly linked and plausibly identical or allelic. Son-killing may be an important yet unrecognized component of other X-linked segregation distorters.
Meiotic drive impacts expression and evolution of X-linked genes in stalk-eyed flies
4155Reinhardt, JAB, C. L.; Paczolt, K. A.; Johns, P. M.; Baker, R. H.; Wilkinson, G. S., PLOS Genetics, 10:e1004362. 2014-01-13 00:00:00.
Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (X-SR) or a standard X chromosome (X-ST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that X-SR and X-ST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on X-SR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.
Analysis of segregation distortion and its relationship to hybrid barriers in rice
4154Reflinur, K, B.; Jang, S. M.; Chu, S. H.; Bordiya, Y.; Akter, M. B.; Lee, J.; Chin, J. H.; Koh, H. J., Rice, 7:3. 2014-01-12 00:00:00.
Segregation distortion (SD) is a frequently observed occurrence in mapping populations generated from crosses involving divergent genotypes. In the present study, ten genetic linkage maps constructed from reciprocal F-2 and BC1F1 mapping populations derived from the parents Dasanbyeo (indica) and Ilpumbyeo (japonica) were used to identify the distribution, effect, and magnitude of the genetic factors underlying the mechanisms of SD between the two subspecies. ResultsSD loci detected in the present study were affected by male function, female function, and zygotic selection. The most pronounced SD loci were mapped to chromosome 3 (transmitted through male gametes), chromosome 5 (transmitted through male gametes), and chromosome 6 (transmitted through female gametes). The level of SD in BC1F1 populations which defined by chi-square value independence multiple tests was relatively low in comparison to F-2 populations. Dasanbyeo alleles were transmitted at a higher frequency in both F-2 and BC1F1 populations, suggesting that indica alleles are strongly favored in inter-subspecific crosses in rice. SD loci in the present study corresponded to previously reported loci for reproductive barriers. In addition, new SD loci were detected on chromosomes 2 and 12. ConclusionThe identification of the distribution of SD and the effect of genetic factors causing SD in genetic mapping populations provides an opportunity to survey the whole genome for new SD loci and their relationships to reproductive barriers. This provides a basis for future research on the elucidation of the genetic mechanisms underlying SD in rice, and will be useful in molecular breeding programs.
Multiple sex chromosomes in the light of female meiotic drive in amniote vertebrates
4153Pokorna, MA, M.; Kratochvil, L., Chromosome Research, 22:35-44. 2014-01-11 00:00:00.
It is notable that the occurrence of multiple sex chromosomes differs significantly between major lineages of amniote vertebrates. In this respect, birds are especially conspicuous, as multiple sex chromosomes have not been observed in this lineage so far. On the other hand, in mammals, multiple sex chromosomes have evolved many times independently. We hypothesize that this contrast can be related to the different involvement of sex-specific sex chromosomes in female meiosis subjected to the female meiotic drive under male versus female heterogamety. Essentially, the male-specific Y chromosome is not involved in female meiosis and is therefore sheltered against the effects of the female meiotic drive affecting the X chromosome and autosomes. Conversely, the Z and W sex chromosomes are both present in female meiosis. Nonrandom segregation of these sex chromosomes as a consequence of their rearrangements connected with the emergence of multiple sex chromosomes would result in a biased sex ratio, which should be penalized by selection. Therefore, the emergence of multiple sex chromosomes should be less constrained in the lineages with male rather than female heterogamety. Our broader phylogenetic comparison across amniotes supports this prediction. We suggest that our results are consistent with the widespread occurrence of female meiotic drive in amniotes.
Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus
4152Patten, MM, Journal of Evolutionary Biology, 27:2360-2370. 2014-01-10 00:00:00.
Most meiotic drivers, such as the t-haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex-specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture.
Transmission distortion affecting human noncrossover but not crossover recombination: A hidden source of meiotic drive
4149Odenthal-Hesse, LB, I. L.; Veselis, A.; Jeffreys, A. J.; May, C. A., PLOS Genetics, 10:e1004106. 2014-01-07 00:00:00.
Author Summary Meiosis is an essential feature of sexual reproduction that maintains chromosome number over generations. This specialised form of cell division creates gametes containing a single copy of each chromosome so that each parent contributes half their genetic information to an offspring. Accurate partitioning first requires intimate association of the two parental copies of each chromosome and concomitant exchange between them. These exchanges consist of both large-scale reciprocal crossovers, essential for correct chromosome segregation, and very localised gene conversion events, or noncrossovers, thought to be involved in correct chromosome pairing. Ordinarily, the reshuffling of genetic variants between generations by recombination will not alter their population frequency only their haplotypic context, with a parent passing on a given variant to 50% of its gametes according to Mendel's law of inheritance. However, by screening for both types of recombinant amongst the sperm DNA of healthy men, we have identified a novel form of biased transmission that is restricted to noncrossovers and favours eventual fixation of one variant over another in the population. This previously undetected source of meiotic drive will not alter recombination propensity but is likely to be a common and potent force acting on the human genome. Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes.
The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive
4145Larracuente, AM, BMC Evolutionary Biology, 14:233. 2014-01-03 00:00:00.
: Satellite DNA can make up a substantial fraction of eukaryotic genomes and has roles in genome structure and chromosome segregation. The rapid evolution of satellite DNA can contribute to genomic instability and genetic incompatibilities between species. Despite its ubiquity and its contribution to genome evolution, we currently know little about the dynamics of satellite DNA evolution. The Responder (Rsp) satellite DNA family is found in the pericentric heterochromatin of chromosome 2 of Drosophila melanogaster. Rsp is well-known for being the target of Segregation Distorter (SD) an autosomal meiotic drive system in D. melanogaster. I present an evolutionary genetic analysis of the Rsp family of repeats in D. melanogaster and its closely-related species in the melanogaster group (D. simulans, D. sechellia, D. mauritiana, D. erecta, and D. yakuba) using a combination of available BAC sequences, whole genome shotgun Sanger reads, Illumina short read deep sequencing, and fluorescence in situ hybridization. Results: I show that Rsp repeats have euchromatic locations throughout the D. melanogaster genome, that Rsp arrays show evidence for concerted evolution, and that Rsp repeats exist outside of D. melanogaster, in the melanogaster group. The repeats in these species are considerably diverged at the sequence level compared to D. melanogaster, and have a strikingly different genomic distribution, even between closely-related sister taxa. Conclusions: The genomic organization of the Rsp repeat in the D. melanogaster genome is complex it exists of large blocks of tandem repeats in the heterochromatin and small blocks of tandem repeats in the euchromatin. My discovery of heterochromatic Rsp-like sequences outside of D. melanogaster suggests that SD evolved after its target satellite and that the evolution of the Rsp satellite family is highly dynamic over a short evolutionary time scale (<240,000 years).
Meiotic drive in mice carrying t-complex in their genome
4180Safronova, LDC, V. L., Russian Journal of Genetics, 49:885-897. 2013-01-18 00:00:00.
The deviation of alleles and chromosomes from Mendelian inheritance is characteristic of the meiotic drive. This review describes the mechanism in question using the best-studied example of transmitted ratio distortion in the heterozygous male mice carrying t-haplotypes. The t-complex is best model for studying the meiotic drive under laboratory conditions. Putative mechanisms of meiotic drive that influence the frequency of t-haplotypes in natural populations are considered, of which prezygotic selection is the most important. The role of meiotic drive in male hybrid sterility is emphasized. The factors and models that determine the phenomenon of meiotic drive are discussed in detail.
Association of polyandry and sex-ratio drive prevalence in natural populations of Drosophila neotestacea
4179Pinzone, CAD, K. A., Proceedings of the Royal Society B-Biological Sciences, 280:20131397. 2013-01-17 00:00:00.
Selfish genetic elements bias their own transmission to the next generation, even at the expense of the fitness of their carrier. Sex-ratio (SR) meiotic drive occurs when an X-chromosome causes Y-bearing sperm to die during male spermatogenesis, so that it is passed on to all of the male's offspring, which are all daughters. How SR is maintained as a stable polymorphism in the absence of genetic suppressors of drive is unknown. Here, we investigate the potential for the female remating rate to affect SR dynamics in natural populations, using the fly Drosophila neotestacea. In controlled laboratory conditions, females from populations where SR is rare mate more often than females from populations where SR is common. Furthermore, only when males mate multiply does the average fertility of SR males relative to wild-type males decrease to a level that can prevent SR from spreading. Our results suggest that differences in the female mating rate among populations may contribute to SR dynamics in the wild, and thus also affect the outcome of this intragenomic conflict. In line with this, we also present evidence of a localized population crash due to SR that may have resulted from habitat fragmentation along with a reduced mating rate.
Diversity and abundance of the abnormal chromosome 10 meiotic drive complex in Zea mays
4174Kanizay, LBP, T.; Lowry, E. G.; Hufford, M. B.; Peterson, D. G.; Ross-Ibarra, J.; Dawe, R. K., Heredity, 110:570-577. 2013-01-12 00:00:00.
Maize Abnormal chromosome 10 (Ab10) contains a classic meiotic drive system that exploits the asymmetry of meiosis to preferentially transmit itself and other chromosomes containing specialized heterochromatic regions called knobs. The structure and diversity of the Ab10 meiotic drive haplotype is poorly understood. We developed a bacterial artificial chromosome (BAC) library from an Ab10 line and used the data to develop sequence-based markers, focusing on the proximal portion of the haplotype that shows partial homology to normal chromosome 10. These molecular and additional cytological data demonstrate that two previously identified Ab10 variants (Ab10-I and Ab10-II) share a common origin. Dominant PCR markers were used with fluorescence in situ hybridization to assay 160 diverse teosinte and maize landrace populations from across the Americas, resulting in the identification of a previously unknown but prevalent form of Ab10 (Ab10-III). We find that Ab10 occurs in at least 75% of teosinte populations at a mean frequency of 15%. Ab10 was also found in 13% of the maize landraces, but does not appear to be fixed in any wild or cultivated population. Quantitative analyses suggest that the abundance and distribution of Ab10 is governed by a complex combination of intrinsic fitness effects as well as extrinsic environmental variability.
Mutations to the piRNA Pathway Component Aubergine Enhance Meiotic Drive of Segregation Distorter in Drosophila melanogaster
4172Gell, SLR, R. A., Genetics, 193:771-784. 2013-01-10 00:00:00.
Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to "cheat" the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non-Sd-bearing (Sd(+)) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germ-line-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.
Mechanism of meiotic drive in mammals
4170Chmatal, LF, K.; Schultz, R. M.; Lampson, M. A., Molecular Biology of the Cell, 24:3775. 2013-01-08 00:00:00.
Meiotic drive is a phenomenon responsible for an unequal representation of alleles or whole chromosomes among gametes as a result of the mechanics of meiotic division (Sandler et Novitski 1957). When it drives segregation of Robertsonian translocations (Rb), a common chromosomal rearrangement in mammals, in oocytes these translocations are either preferentially maintained in the egg or preferentially expelled to the polar body during meiosis I (MI), thus being either transmitted or excluded from the next generation. Because Rb translocations are formed by fusion of two acrocentric chromosomes creating one metacentric chromosome, subsequent accumulation and fixation of these fusions over time leads to a change in karyotype (Castaglia 1982, Villena et Sapienza 2001). Despite the importance of this phenomenon for evolution and speciation, the underlying mechanisms of meiotic drive are unknown. We tested a model of meiotic drive based on three elements: (1) an asymmetric trivalent that forms in MI when a metacentric fusion pairs with the two homologous acrocentric chromosomes, (2) preferential orientation of the trivalent on an asymmetric spindle, and (3) orientation of the asymmetric spindle with one side preferentially facing the cortex. We find reduced levels of kinetochore proteins in fusion centromeres compared to the homologous acrocentric centromeres, suggesting that the trivalent asymmetry is based on differential centromere strength. We also find that stability of MI spindle microtubules is influenced by proximity to the cortex, leading to asymmetric spindles with more stable microtubules oriented towards the cortex. These MTs preferentially bind the fusion centromere, which orients the metacentric Rb fusion chromosome towards the cortex for eventual segregation to the polar body.Together, our data provide evidence for a model to explain the biased segregation of Rb translocations in mammalian oocytes.
The contribution of female meiotic drive to the evolution of neo-sex chromosomes
4197Yoshida, KK, J., Evolution, 66:3198-3208. 2012-01-15 00:00:00.
Sex chromosomes undergo rapid turnover in certain taxonomic groups. One of the mechanisms of sex chromosome turnover involves fusions between sex chromosomes and autosomes. Sexual antagonism, heterozygote advantage, and genetic drift have been proposed as the drivers for the fixation of this evolutionary event. However, all empirical patterns of the prevalence of multiple sex chromosome systems across different taxa cannot be simply explained by these three mechanisms. In this study, we propose that female meiotic drive may contribute to the evolution of neo-sex chromosomes. The results of this study showed that in mammals, the XY1Y2 sex chromosome system is more prevalent in species with karyotypes of more biarmed chromosomes, whereas the X1X2Y sex chromosome system is more prevalent in species with predominantly acrocentric chromosomes. In species where biarmed chromosomes are favored by female meiotic drive, X-autosome fusions (XY1Y2 sex chromosome system) will be also favored by female meiotic drive. In contrast, in species with more acrocentric chromosomes, Y-autosome fusions (X1X2Y sex chromosome system) will be favored just because of the biased mutation rate toward chromosomal fusions. Further consideration should be given to female meiotic drive as a mechanism in the fixation of neo-sex chromosomes.
From genes to games: Cooperation and cyclic dominance in meiotic drive
4196Traulsen, AR, F. A., Journal of Theoretical Biology, 299:120-125. 2012-01-14 00:00:00.
Evolutionary change can be described on a genotypic level or a phenotypic level. Evolutionary game theory is typically thought of as a phenotypic approach, although it is frequently argued that it can also be used to describe population genetic evolution. Interpreting the interaction between alleles in a diploid genome as a two player game leads to interesting alternative perspectives on genetic evolution. Here we focus on the case of meiotic drive and illustrate how meiotic drive can be directly and precisely interpreted as a social dilemma, such as the prisoners dilemma or the snowdrift game, in which the drive allele takes more than its fair share. Resistance to meiotic drive can lead to the well understood cyclic dominance found in the rock-paper-scissors game. This perspective is well established for the replicator dynamics, but there is still considerable ground for mutual inspiration between the two fields. For example, evolutionary game theorists can benefit from considering the stochastic evolutionary dynamics arising from finite population size. Population geneticists can benefit from game theoretic tools and perspectives on genetic evolution. (c) 2011 Elsevier Ltd. All rights reserved.
No evidence of mate discrimination against males carrying a sex ratio distorter in Drosophila pseudoobscura
4194Price, TARL, Z.; Smith, D. T.; Hurst, G. D. D.; Wedell, N., Behavioral Ecology and Sociobiology, 66:561-568. 2012-01-12 00:00:00.
Selfish genetic elements (SGEs) that spread by manipulating spermatogenesis often have highly deleterious effects on males that carry them. Females that mate with male carriers of SGEs can also suffer significant costs: they receive fewer and poorer-quality sperm, their offspring will inherit the deleterious allele, and the sex ratio of their offspring will be biased towards the more common sex. To counter these costs, females are therefore expected to prefer to mate with males that do not carry sex ratio distorters or other deleterious selfish genetic elements. However, despite the potential costs, there are few examples of female choice against males carrying SGEs. We searched for evidence of a female preference in fruit fly Drosophila pseudoobscura against males carrying a costly meiotic driving X-chromosome Sex Ratio (SR). In a series of five non-competitive mate preference experiments, we find no evidence that females prefer to mate with non-SR males. Our use of five separate experiments, involving more than 800 females, makes it unlikely that this lack of a difference was due to low power or simple chance. We suggest that the lack of female choice against SGE-carrying males may be due to strong selection on SGEs to be indistinguishable from alternative alleles. Furthermore, polyandry, either in direct response to receiving an ejaculate from an SGE-carrying male or carried out indiscriminately when at risk of mating with carriers, may be an alternative response by females to limit the exposure of their offspring to SGEs.
Evaluating the evidence for transmission distortion in human pedigrees
4193Meyer, WKA, B.; Ober, C.; Ebner, T.; Tiemann-Boege, I.; Hudson, R. R.; Przeworski, M., Genetics, 191:215-232. 2012-01-11 00:00:00.
Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term "transmission distortion" (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies.
The Selfish Segregation Distorter Gene Complex of Drosophila melanogaster
4190Larracuente, AMP, D. C., Genetics, 192:33-53. 2012-01-08 00:00:00.
Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD+ spermatids so that SD/SD+ males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci-the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)-and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.
Molecular dissection of Neurospora Spore killer meiotic drive elements
4187Hammond, TMR, D. G.; Xiao, H.; Shiu, P. K. T., Proceedings of the National Academy of Sciences of the United States of America, 109:12093-12098. 2012-01-05 00:00:00.
Meiotic drive is a non-Mendelian inheritance phenomenon in which certain selfish genetic elements skew sexual transmission in their own favor. In some cases, progeny or gametes carrying a meiotic drive element can survive preferentially because it causes the death or malfunctioning of those that do not carry it. In Neurospora, meiotic drive can be observed in fungal spore killing. In a cross of Spore killer (Sk) x WT (Sk-sensitive), the ascospores containing the Spore killer allele survive, whereas the ones with the sensitive allele degenerate. Sk-2 and Sk-3 are the most studied meiotic drive elements in Neurospora, and they each theoretically contain two essential components: a killer element and a resistance gene. Here we report the identification and characterization of the Sk resistance gene, rsk (resistant to Spore killer). rsk seems to be a fungal-specific gene, and its deletion in a killer strain leads to self-killing. Sk-2, Sk-3, and naturally resistant isolates all use rsk for resistance. In each killer system, rsk sequences from an Sk strain and a resistant isolate are highly similar, suggesting that they share the same origin. Sk-2, Sk-3, and sensitive rsk alleles differ from each other by their unique indel patterns. Contrary to long-held belief, the killer targets not only late but also early ascospore development. The WT RSK protein is dispensable for ascospore production and is not a target of the spore-killing mechanism. Rather, a resistant version of RSK likely neutralizes the killer element and prevents it from interfering with ascospore development.
A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegans
4208Seidel, HSA, M.; Li, J. L.; van Oudenaarden, A.; Rockman, M. V.; Kruglyak, L., PLOS Biology, 9:e1001115. 2011-01-06 00:00:00.
The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it.
Selective microspore abortion correlated with aneuploidy: an indication of meiotic drive
4204Furness, CAR, P. J., Sexual Plant Reproduction, 24:1-8. 2011-01-02 00:00:00.
Selective megaspore abortion (monomegaspory) probably arose once in seed plants and occurs routinely in more than 70% of angiosperm species, representing one of the key characters of a heterosporous life history. In contrast, selective microspore abortion leading to pollen dispersal as pseudomonads (here termed monomicrospory) apparently arose at least twice independently within angiosperms, though it occurs in a limited number of taxa. Remarkably, similar examples of monomicrospory occur in members of two distantly related angiosperm families: the sedge family (Cyperaceae) and the epacrid subfamily (Styphelioideae) of the eudicot family Ericaceae. In sedges, monomicrospory is derived directly from normal tetrads, whereas epacrid pseudomonads apparently evolved via an intermediate stage, in which variable sterility occurs in a single tetrad. Our comparison of these two examples of selective microspore abortion highlights a correlation with aneuploidy, indicating that non-random chromosome segregation caused by monomicrospory could drive chromosomal mutations to rapid fixation through meiotic drive.
Polar bodies–more a lack of understanding than a lack of respect
8196S. Schmerler and G. M. Wessel, Molecular Reproduction and Development, 78:3-8. 2010-12-30 20:20:23.
Polar bodies are as diverse as the organisms that produce them. Although in many animals these cells often die following meiotic maturation of the oocyte, in other organisms they are an essential and diverse part of embryonic development. Here we highlight some of this diversity and summarize the evolutionary basis for their
Changes in sperm tail development associated with Y chromosome meiotic drive leading to an excess of males in the medfly Ceratitis capitata (Diptera: Tephritidae)
4218Rendon, PAB, R. D.; Wood, R. J., Biological Journal of the Linnean Society, 101:351-359. 2010-01-16 00:00:00.
The Mediterranean fruit fly Ceratitis capitata (Wied.) normally produces the sexes in equal ratio but strains carrying the Y chromosome meiotic drive MP (male-producing) factor show an excess of males. This is associated with a loss of sperm, and abnormal sperm structure in terms of multiple axonemes, atypical numbers of mitochondrial derivatives, and sometimes an incorrect initial orientation of paracrystalline bodies to the axoneme. Sperms are bundled together within spermatocysts, and those with depleted content and abnormalities occur in the same MP testes as normal spermatocysts. The maximum number of sperms per cyst in control strains was 256, each with a single axoneme originating from a single centriole (kinetosome). The maximum per cyst in MP strains was also 256 but MP cysts contained up to 300 axonemes, providing evidence of multiplication of centrioles. The structural changes in MP sperm are discussed in relation to similar abnormalities reported in the mosquito Aedes aegypti inheriting the Y chromosome meiotic drive haplotype MD. The evolutionary significance of this phenomenon is considered. (C) 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 351-359.
The role of meiotic drive in hybrid male sterility
4217McDermott, SRN, M. A. F., Philosophical Transactions of the Royal Society B-Biological Sciences, 365:1265-1272. 2010-01-15 00:00:00.
Meiotic drive causes the distortion of allelic segregation away from Mendelian expected ratios, often also reducing fecundity and favouring the evolution of drive suppressors. If different species evolve distinct drive-suppressor systems, then hybrid progeny may be sterile as a result of negative interactions of these systems' components. Although the hypothesis that meiotic drive may contribute to hybrid sterility, and thus species formation, fell out of favour early in the 1990s, recent results showing an association between drive and sterility have resurrected this previously controversial idea. Here, we review the different forms of meiotic drive and their possible roles in speciation. We discuss the recent empirical evidence for a link between drive and hybrid male sterility, also suggesting a possible mechanistic explanation for this link in the context of chromatin remodelling. Finally, we revisit the population genetics of drive that allow it to contribute to speciation.
Segregation distortion and the evolution of sex-determining mechanisms
4216Kozielska, MW, F. J.; Beukeboom, L. W.; Pen, I., Heredity, 104:100-112. 2010-01-14 00:00:00.
Segregation distorters are alleles that distort normal segregation in their own favour. Sex chromosomal distorters lead to biased sex ratios, and the presence of such distorters, therefore, may induce selection for a change in the mechanism of sex determination. The evolutionary dynamics of distorter-induced changes in sex determination has only been studied in some specific systems. Here, we present a generic model for this process. We consider three scenarios: a driving X chromosome, a driving Y chromosome and a driving autosome with a male-determining factor. We investigate how the invasion prospects of a new sex-determining factor are affected by the strength of distortion and the fitness effect of the distorting allele. Our models show that in many cases, segregation distortion does create selection pressure, allowing novel sex-determining alleles to spread. When distortion leads to female-biased sex ratios, a new masculinizing gene can invade, leading to a new male heterogametic system. When distortion leads to male-biased sex ratios, a feminizing factor can invade and cause a switch to female heterogamety. In many cases, the distorter-induced change in the sex-determining system eventually leads to loss of the distorter from the population. Hence, the presence of sex chromosomal distorters will often only be transient, and the distorters may remain unnoticed. The role of segregation distortion in the evolution of sex determination may, therefore, be underestimated. Heredity (2010) 104, 100-112; doi:10.1038/hdy.2009.104; published online 12 August 2009
Testosterone has a long-term effect on primary sex ratio of first eggs in pigeons-in search of a mechanism
4223Goerlich, VCD, C.; Schaafsma, S. M.; Groothuis, T. G. G., General and Comparative Endocrinology, 163:184-192. 2009-01-21 00:00:00.
Despite accumulating evidence that birds, in which females are the heterogametic sex, are able to manipulate primary offspring sex ratio, the underlying mechanism remains elusive. Steroid hormones. which govern female reproduction and are also accumulated by the developing follicle could potentially affect primary sex ratio by differential follicle development in relation to future sex and meiotic drive, or by sex specific influence on oocyte abortion or fertilization. So far, experimental results on the involvement of maternal testosterone (T) in offspring sex manipulation are ambiguous. To investigate the effect of T on primary sex ratio and elucidate underlying mechanisms, we elevated circulating T levels in female homing pigeons (Columba livia). During the course of the experiment females produced three clutches-before and during T implantation, and one year after implant removal. Intriguingly, first eggs, but not second eggs of T females were significantly male biased relative to sham-implanted controls. One year after cessation of the treatment the male bias was still present, indicating long-term effects on female reproductive physiology. T treatment did not affect maternal body condition, nor was body condition correlated with offspring sex ratio. Our data on timing of oviposition, lack of infertile eggs, and yolk weight indicate a possible role for sex specific follicle abortion, perhaps in combination with meiotic drive. However, despite T treatment elevating maternal plasma levels, egg yolk T concentrations did not differ between treatment groups and did not vary with embryo sex, suggesting that yolk T is not involved in meiotic drive. (C) 2009 Elsevier Inc. All rights reserved.
Molecular signature of epistatic selection: interrogating genetic interactions in the sex-ratio meiotic drive of Drosophila simulans
4222Chevin, LMB, H.; Montchamp-Moreau, C.; Hospital, F., Genetics Research, 91:171-182. 2009-01-20 00:00:00.
Fine scale analyses Of signatures of selection allow assessing quantitative aspects of a Species' evolutionary genetic history, such as the strength of selection on genes. When several selected loci lie in the same genomic region, their epistatic interactions may also be investigated. Here. we Study how the neutral polymorphism pattern was shaped by two close recombining loci that cause 'sex-ratio' meiotic drive in Drosophila simulans, as an example of strong selection with potentially strong epistasis. We compare the polymorphism data observed in a natural population with the results of forward stochastic simulations under several contexts of epistasis between the candidate loci for the drive. We compute the likelihood of different possible scenarios. in order to determine which configuration is most consistent with the data. Our results highlight that fine scale analyses of well-chosen candidate genomic regions provide information-rich data that can be used to investigate the genotype-phenotype-fitness map. which can hardly be Studied in genome-wide analyses. We also emphasize that initial conditions and time of observation (here, time after the Interruption Of a partial selective sweep) are crucial parameters in the interpretation of real data, while these are often overlooked in theoretical studies.
Large-scale selective sweep among Segregation Distorter chromosomes in African populations Drosophila melanogaster
4229Presgraves, DCG, P. R.; Cherukuri, A.; Lyttle, T. W., PLOS Genetics, 5:e1000463. 2009-01-07 00:00:00.
Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD(+) males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1-5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (similar to 2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.
Drive and sperm: The evolution and genetics of male meiotic drive
4228Presgraves, D, Sperm Biology: an Evolutionary Perspective, 12:471-506. 2009-01-06 00:00:00.
Some selfish genetic elements in eukaryotic genomes have been harnessed to perform essential functions for their hosts, whereas others have gained transmission advantages at the expense of their hosts. Meiotic drive elements are particularly dramatic examples of the latter. Meiotic drive is the unequal—and thus non-Mendelian—transmission of alternative alleles or chromosomes from heterozygotes. Most drive elements achieve greater than Mendelian transmission from their carriers by excluding, impairing or killing competing alternative gametes. The best-characterized drive elements are the Segregation Distorter (SD) complex in the fruitfly Drosophila melanogaster and the t-haplotype in the Mus house mouse species. Despite being found in very distantly related species, both meiotic drive systems share genetic and chromosomal features that appear to characterize meiotic drive systems in general. For these, and all systems characterized to date, drive involves an interaction between at least two loci in which a trans-acting drive allele at one locus impairs transmission of sensitive alleles at a cis-acting target locus. In effect, the drive allele produces a toxin that incapacitates sperm bearing sensitive forms of the target. Drive chromosomes bear a driver and a drive-insensitive target, whereas non-drive chromosomes lack the driver and typically carry a drivesensitive target. This chapter reviews the genetics, molecular basis, and evolutionary history of several well-characterized drive systems, and considers the impact of drive on spermatogenesis and sperm competition, including potential evolutionary responses of organisms to drive.
Major evolutionary transitions in centromere complexity
4226Malik, HSH, S., Cell, 138:1067-1082. 2009-01-04 00:00:00.
Centromeres are chromosomal elements that are both necessary and sufficient for chromosome segregation. However, the puzzlingly broad range in centromere complexity, from simple "point" centromeres to multi-megabase arrays of DNA satellites, has defied explanation. We posit that ancestral centromeres were epigenetically defined and that point centromeres, such as those of budding yeast, have derived from the partitioning elements of selfish plasmids. We further propose that the larger centromere sizes in plants and animals and the rapid evolution of their centromeric proteins is the result of an intense battle for evolutionary dominance due to the asymmetric retention of only one product of female meiosis.
Defects in nuclear transport enhance segregation distortion
4242McElroy, JMM, R. A.; McLean, J. R., Fly, 2:280-290. 2008-01-20 00:00:00.
The equal segregation of chromosomes into gametes is a central tenet of Mendelian genetics. It is this process that is responsible for generating predictable outcomes of crosses, as well as subjecting all chromosomes to the natural selective pressures that exert themselves on a population. Meiotic drive systems violate the principle, and result in a distortion of normal Mendelian ratios. Examples of such meiotic drive systems exist in many organisms, including insects, mammals and plants (reviewed in Lyttle).1 The most clearly understood of these is the Segregation Distorter (SD) system in Drosophila melanogaster. SD was first observed because males carrying one SD chromosome and one normal (SD+) chromosome failed to transmit the normal chromosome to their offspring, causing transmission ratios of near 100% of the SD chromosome.2 T
Broadening the application of evolutionarily based genetic pest management
4237Gould, F, Evolution, 62:500-510. 2008-01-15 00:00:00.
Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental damage and economic losses in agriculture and forestry Rodents transmit diseases and cause major pre- and postharvest losses, especially in less affluent countries. Each of these problems might benefit from the developing field of Genetic Pest Management that is conceptually based on principles of evolutionary biology This article briefly describes the history of this field, new molecular tools in this field, and potential applications of those tools. There will be a need for evolutionary biologists to interact with researchers and practitioners in a variety of other fields to determine the most appropriate targets for genetic pest management, the most appropriate methods for specific targets, and the potential of natural selection to diminish the effectiveness of genetic pest management. In addition to producing environmentally sustainable pest management solutions, research efforts in this area could lead to new insights about the evolution of selfish genetic elements in natural systems and will provide students with the opportunity to develop a more sophisticated understanding of the role of evolutionary biology in solving societal problems.
Centromere-associated female meiotic drive entails male fitness costs in Monkeyflowers
4236Fishman, LS, A., Science, 322:1559-1562. 2008-01-14 00:00:00.
Female meiotic drive, in which paired chromosomes compete for access to the egg, is a potentially powerful but rarely documented evolutionary force. In interspecific monkeyflower ( Mimulus) hybrids, a driving M. guttatus allele ( D) exhibits a 98: 2 transmission advantage via female meiosis. We show that extreme interspecific drive is most likely caused by divergence in centromere- associated repeat domains and document cytogenetic and functional polymorphism for drive within a population of M. guttatus. In conspecific crosses, D had a 58: 42 transmission advantage over nondriving alternative alleles. However, individuals homozygous for the driving allele suffered reduced pollen viability. These fitness effects and molecular population genetic data suggest that balancing selection prevents the fixation or loss of D and that selfish chromosomal transmission may affect both individual fitness and population genetic load.
Selective sweeps in a 2-locus model for sex-ratio meiotic drive in Drosophila simulans
4235Derome, NB, E.; Ogereau, D.; Veuille, M.; Montchamp-Moreau, C., Molecular Biology and Evolution, 25:409-416. 2008-01-13 00:00:00.
A way to identify loci subject to positive selection is to detect the signature of selective sweeps in given chromosomal regions. It is revealed by the departure of DNA polymorphism patterns from the neutral equilibrium predicted by coalescent theory. We surveyed DNA sequence variation in a region formerly identified as causing "sex-ratio" meiotic drive in Drosophila simulans. We found evidence that this system evolved by positive selection at 2 neighboring loci, which thus appear to be required simultaneously for meiotic drive to occur. The 2 regions are approximately 150-kb distant, corresponding to a genetic distance of 0.1 cM. The presumably large transmission advantage of chromosomes carrying meiotic drive alleles at both loci has not erased the individual signature of selection at each locus. This chromosome fragment combines a high level of linkage disequilibrium between the 2 critical regions with a high recombination rate. As a result, 2 characteristic traits of selective sweeps-the reduction of variation and the departure from selective neutrality in haplotype tests-show a bimodal pattern. Linkage disequilibrium level indicates that, in the natural population from Madagascar used in this study, the selective sweep may be as recent as 100 years.
Rapid evolution of yeast centromeres in the absence of drive
4233Bensasson, DZ, M.; Burt, A.; Koufopanou, V., Genetics, 178:2161-2167. 2008-01-11 00:00:00.
To find the most rapidly evolving regions in the yeast genome we compared most of chromosome III from three closely related lineages of the wild yeast Saccharomyces paradoxits. Unexpectedly, the centromere appears to be the fastest-evolving part of the chromosome, evolving even faster than DNA sequences unlikely to be under selective constraint (i.e., synonymous sites after correcting for codon usage bias and remnant transposable elements). Centromeres on other chromosomes also show an elevated rate of nucleotide substitution. Rapid centromere evolution has also been reported for some plants and animals and has been attributed to selection for inclusion in the egg or the ovule at female meiosis. But Saccharomyces yeasts have symmetrical meioses with all four products surviving, thus providing no opportunity for meiotic drive. In addition, yeast centromeres show the high levels of polymorphism expected tinder a neutral model of molecular evolution. We suggest that yeast centromeres suffer an elevated rate of mutation relative to other chromosomal regions and they change through a process of "centromere drift," not drive.
Meiotic drive and sex determination: molecular and cytological mechanisms of sex ratio adjustment in birds
4246Rutkowska, JB, A. V., Philosophical Transactions of the Royal Society B-Biological Sciences, 363:1675-1686. 2008-01-04 00:00:00.
Differences in relative fitness of male and female offspring across ecological and social environments should favour the evolution of sex-determining mechanisms that enable adjustment of brood sex ratio to the context of breeding. Despite the expectation that genetic sex determination should not produce consistent bias in primary sex ratios, extensive and adaptive modifications of offspring sex ratio in relation to social and physiological conditions during reproduction are often documented. Such discordance emphasizes the need for empirical investigation of the proximate mechanisms for modifying primary sex ratios, and suggests epigenetic effects on sex-determining mechanisms as the most likely candidates. Birds, in particular, are thought to have an unusually direct opportunity to modify offspring sex ratio because avian females are heterogametic and because the sex-determining division in avian meiosis occurs prior to ovulation and fertilization. However, despite evidence of strong epigenetic effects on sex determination in pre-ovulatory avian oocytes, the mechanisms behind such effects remain elusive. Our review of molecular and cytological mechanisms of avian meiosis uncovers a multitude of potential targets for selection on biased segregation of sex chromosomes, which may reflect the diversity of mechanisms and levels on which such selection operates in birds. Our findings indicate that pronounced differences between sex chromosomes in size, shape, size of protein bodies, alignment at the meiotic plate, microtubule attachment and epigenetic markings should commonly produce biased segregation of sex chromosomes as the default state, with secondary evolution of compensatory mechanisms necessary to maintain unbiased meiosis. We suggest that it is the epigenetic effects that modify such compensatory mechanisms that enable context-dependent and precise adjustment of primary sex ratio in birds. Furthermore, we highlight the features of avian meiosis that can be influenced by maternal hormones in response to environmental stimuli and may account for the precise and adaptive patterns of offspring sex ratio adjustment observed in some species.
Sexually antagonistic “Zygotic Drive” of the sex Chromosomes
4245Rice, WRG, S.; Friberg, U., PLOS Genetics, 4:e1000313. 2008-01-03 00:00:00.
Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive'', because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race'' between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.
Selfish genetic elements promote polyandry in a fly
4244Price, TARH, D. J.; Lewis, Z.; Hurst, G. D. D.; Wedell, N., Science, 322:1241-1243. 2008-01-02 00:00:00.
It is unknown why females mate with multiple males when mating is frequently costly and a single copulation often provides enough sperm to fertilize all a female's eggs. One possibility is that remating increases the fitness of offspring, because fertilization success is biased toward the sperm of high- fitness males. We show that female Drosophila pseudoobscura evolved increased remating rates when exposed to the risk of mating with males carrying a deleterious sex ratio- distorting gene that also reduces sperm competitive ability. Because selfish genetic elements that reduce sperm competitive ability are generally associated with low genetic fitness, they may represent a common driver of the evolution of polyandry.
Viability effects and not meoitic drive cause dramatic departures from Mendelian inheritance for malic enzyme in hybrids of Tigriopus californicus populations
4258Willett, CSB, J. N., Journal of Evolutionary Biology, 20:1196-1205. 2007-01-16 00:00:00.
The genetic basis of post-zygotic reproductive isolation is beginning to be untangled in closely related species, but less is known about the genetics of reproductive isolation between divergent populations. Here, two genes encoding malic enzyme (ME) are isolated from the copepod Tigriopus californicus and their influence upon lowered viability in F-2 hybrids of genetically divergent populations is determined. Each ME gene has diverged extensively between T. californicus populations and one gene shows evidence for a recent selective sweep. Segregation patterns of genotypes for both ME genes in adult F-2 hybrids reveal dramatic departures from Mendelian inheritance, deviations that are not seen in F-2 nauplii implying that selection is acting during development based upon the genotype at these ME genes. These results imply that selection against deleterious gene combinations and not aberrant segregation (i.e. meiotic drive) is likely to lead to dramatic departures from Mendelian inheritance observed in these crosses.
A sex-ratio meiotic drive system in Drosophila simulans. I: An autosomal suppressor
4256Tao, YM, J. P.; Araripe, L.; Ke, Y.; Hartl, D. L., PLOS Biology, 5:2560-2575. 2007-01-14 00:00:00.
Sex ratio distortion (sex-ratio for short) has been reported in numerous species such as Drosophila, where distortion can readily be detected in experimental crosses, but the molecular mechanisms remain elusive. Here we characterize an autosomal sex-ratio suppressor from D. simulans that we designate as not much yang (nmy, polytene chromosome position 87F3). Nmy suppresses an X-linked sex-ratio distorter, contains a pair of near-perfect inverted repeats of 345 bp, and evidently originated through retrotransposition from the distorter itself. The suppression is likely mediated by sequence homology between the suppressor and distorter. The strength of sex-ratio is greatly enhanced by lower temperature. This temperature sensitivity was used to assign the sex-ratio etiology to the maturation process of the Y-bearing sperm, a hypothesis corroborated by both light microscope observations and ultrastructural studies. It has long been suggested that an X-linked sex-ratio distorter can evolve by exploiting loopholes in the meiotic machinery for its own transmission advantage, which may be offset by other changes in the genome that control the selfish distorter. Data obtained in this study help to understand this evolutionary mechanism in molecular detail and provide insight regarding its evolutionary impact on genomic architecture and speciation.
Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA
4254Raju, NBM, R. L.; Shiu, P. T., Genetics, 176:43-52. 2007-01-12 00:00:00.
In Neurosphora, crassa., pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA (MSUD). Two genes required for MSUD have been described previously: Sad-1 (Suppressor of ascus dominance), encoding an RNA-directed RNA polymerase, and sad-2, encoding a protein that controls the perinuclear localization of SAD-1. Inactivation of either sad-1 or sad-2 suppresses MSUD. We have now shown that MSUD is also suppressed by either of two Spore killer strains, Sk-2 and Sk-3. These were both known to contain a haplotype segment that behaves as a meiotic drive element in heterozygous crosses of killer X sensitive. Progeny ascospores not carrying the killer element fail to mature and are inviable. Crosses homozygous for either of the killer haplotypes suppress MSUD even though ascospores are not killed. The killer activity maps to the same 30-unit-long region within which recombination is suppressed in killer X sensitive crosses. We suggest that the region contains a suppressor of MSUD.
Meiotic drive by the Y-linked D gene in Aedes aegypti (L.) (Diptera : Culicidae) is associated with disruption of spermiogenesis, leading to premature senescence of spermatozoa
4253Owusu-Daaku, KOB, R. D.; Wood, R. J., Arthropod Structure & Development, 36:233-243. 2007-01-11 00:00:00.
Y chromosome meiotic drive in the mosquito Aedes aegypti, due to the gene D (Distorter) in coupling with M (male determination) [the MD haplotype], is associated with spermiogenic disruption, leading to senescence, at a rate Proportionate to male excess. Spermiogenesis was compared between 'Enhanced Mutant' males with a strongly female-depleted sex ratio (8.9% females), 'Mutant' males showing a lesser degree of distortion (38.3% females), and two controls with normal sex ratios (51.2% and 49.2% females). Sections of testes dissected front mature pupae and adults aged 0, 4, 8, 12 and 16 days were examined by transmission electron microscopy. A difference between Mutant and control spermiogenesis was apparent as early as the pupal stage when some Mutant spermatids showed extra tail elements (axonemes and/or mitochondrial derivatives). The same was true of Enhanced Mutant males but to a more extreme degree. Sperm senescence was evident in Enhanced Mutant testes from day 0 of adult life but in Mutant testes not until day 4. Progressive disorganisation was associated with many loose organelles, and disturbance of the anterior-posterior axis of gamete differentiation within the testis. Degenerative changes of a similar kind in the controls did not become apparent until day 8. These findings are discussed with respect to other characteristics of this meiotic drive system, in terms of a theory of inhibition of reduction division in spermatogenesis associated with fragmentation of the X chromosome, leading to the formation of a restitution nucleus as early as rnetaphase 1. (c) 2007 Elsevier Ltd. All rights reserved.
Identification and characterization of segregation distortion loci along chromosome 5B in tetraploid wheat
4252Kumar, SG, B. S.; Faris, J. D., Molecular Genetics and Genomics, 278:187-196. 2007-01-10 00:00:00.
Segregation distortion genes are widespread in plants and animals and function by their effect on competition among gametes for preferential fertilization. In this study, we evaluated the segregation distortion of molecular markers in multiple reciprocal backcross populations derived from unique cytogenetic stocks involving the durum cultivar Langdon (LDN) and wild emmer accessions that allowed us to study the effects of chromosome 5B in isolation. No segregation distortion of female gametes was observed, but three populations developed to analyze segregation of male gametes had genomic regions containing markers with skewed segregation ratios. One region of distortion was due to preferential transmission of LDN alleles over wild emmer alleles through male gametes. Another region required the presence of LDN 5B chromosomes in the female for preferential fertilization by male gametes harboring LDN alleles indicating that the corresponding genes in the female gametes can govern genes affecting segregation distortion of male gametes. A third region of distortion was the result of preferential transmission of wild emmer alleles over LDN alleles through male gametes. These results indicate the existence of different distorter/meiotic drive elements among different genotypes and show that distortion factors along wheat chromosome 5B differ in chromosomal location as well as underlying mechanisms.
Introducing desirable transgenes into insect populations using Y-linked meiotic drive – A theoretical assessment
4251Huang, YXM, K.; Lloyd, A. L.; Gould, F., Evolution, 61:717-726. 2007-01-09 00:00:00.
The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Winked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.
Genetic strategies for controlling mosquito-borne diseases
6191F. Gould, K. Magori and Y. Huang, American Scientist, 94:238. 2006-05-03 19:19:14.
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities
The hitchhiking effect of an autosomal meiotic drive gene
4263Chevin, LMH, F., Genetics, 173:1829-1832. 2006-01-21 00:00:00.
Transmission-ratio distortion is a departure from a 1:1 segregation of alleles in the gametes of a heterozygous individual. The so-called driving allele is strongly selected regardless of its effect on the fitness of the carrying individual. It may then have an important impact on neutral polymorphism due to the genetic hitchhiking effect. We study this hitchhiking effect in the case of true meiotic drive in autosomes and show that it is more dependent on the recombination rate than in the classical case of a gene positively selected at the organism level.
Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni
4271Wilkinson, GSJ, P. M.; Kelleher, E. S.; Muscedere, M. L.; Lorsong, A., Journal of Evolutionary Biology, 19:1851-1860. 2006-01-09 00:00:00.
Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of X-SR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that X-SR/X-ST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.
Segregation distortion in Arabidopsis C24/Col-0 and Col-0/C24 recombinant inbred line populations is due to reduced fertility caused by epistatic interaction of two loci
4270Torjek, OW-W, H.; Meyer, R. C.; von Korff, M.; Kusterer, B.; Rautengarten, C.; Altmann, T., Theoretical and Applied Genetics, 113:1551-1561. 2006-01-08 00:00:00.
A new large set of reciprocal recombinant inbred lines (RILs) was created between the Arabidopsis accessions Col-0 and C24 for quantitative trait mapping approaches, consisting of 209 Col-0 x C24 and 214 C24 x Col-0 F-7 RI lines. Genotyping was performed using 110 evenly distributed framework single nucleotide polymorphism markers, yielding a genetic map of 425.70 cM, with an average interval of 3.87 cM. Segregation distortion (SD) was observed in several genomic regions during the construction of the genetic map. Linkage disequilibrium analysis revealed an association between a distorted region at the bottom of chromosome V and a non-distorted region on chromosome IV. A detailed analysis of the RILs for these two regions showed that an SD occurred when homozygous Col-0 alleles on chromosome IV coincided with homozygous C24 alleles at the bottom of chromosome V. Using nearly isogenic lines segregating for the distorted region we confirmed that this genotypic composition leads to reduced fertility and fitness.
Male biased sex ratio in the Mediterranean fruit fly Ceratitis capitata, an example of Y-chromosome meiotic drive
4268Shahjahan, RMR, P. A.; Cook, L. M.; Wood, R. J., Heredity, 96:464-470. 2006-01-06 00:00:00.
A case of Y-chromosome meiotic drive is reported in the Mediterranean fruit fly Ceratitis capitata. It arose in an irradiated male and results in excess of males. Male excess is inherited strictly from father to son. A Y-linked factor MP (male producer) is proposed. Higher drive can be selected, but distortion declines rapidly in the absence of selection. Hybrid males from crosses between driving males and nondriving females also show drive but to a reduced extent, suggesting the action of suppressors. Sex ratio distortion is independent of postzygotic mortality, and is not associated with an obvious chromosome arrangement. Spermiogenesis in driving males is characterised by abnormalities in sperm tails and reduced numbers in some sperm cysts, whereas neighbouring cysts of the same MP testis are essentially wild type. The average number of missing sperms plus deformed sperms approximates to the average depression in female recovery among the progenies of siblings, suggesting that most of the missing or abnormal sperms would have given rise to females, that is, they would have been X-bearing. To explain the heterogeneity between neighbouring cysts, a theory is proposed that links it to variation in X-chromosome sensitivity to MP, arising by random suppression of the genetic basis of sensitivity during the six mitotic divisions in the origin of the cyst from its stem cell before meiosis.
The maize Ab 10 meiotic drive system maps to supernumerary sequences in a large complex haplotype
4267Mroczek, RJM, J. R.; Luce, A. C.; Hiatt, E. N.; Dawe, R. K., Genetics, 174:145-154. 2006-01-05 00:00:00.
The meiotic drive system on maize abnormal chromosome 10 (Ab10) is contained within a terminal domain of chromatin that extends the long arm of Ab10 to similar to 1.3 times the size of normal chromosome 10L. Ab10 type I (Ab10-I) does not recombine with normal chromosome 10 (N10) over an similar to 32-cM terminal region of the long arm. Comparative RFLP mapping demonstrates that multiple independent rearrangements are responsible for the current organization of Ab10-I, including a set of nested inversions and at least one long supernumerary segment at the end of the chromosome. Four major meiotic drive functions, i.e., the recombination effect, smd3, 180-bp neocentromere activity, and the distal tip function, all map to the distal supernumerary segment. TR-1-mediated neocentromere activity (the fifth known drive function) is nonessential in the type II variant of Ab10 and maps to a central region that may include a second supernumerary insertion. Both neocentromere activity and the recombination effect behave as dominant gain-of-function mutations, consistent with the view that meiotic drive involves new or alien gene products. These and other data suggest that the Ab10 meiotic drive system was initially acquired from a related species and that a complex haplotype evolved around it.
Transmission ratio distortion in the human body louse, Pediculus humanus (Insecta : Phthiraptera)
4264McMeniman, CJB, S. C., Heredity, 96:63-68. 2006-01-02 00:00:00.
We studied inheritance at three microsatellite loci in eight F-1 and two F-2 families of the body (clothes) louse of humans, Pediculus humanus. The alleles of heterozygous female-parents were always inherited in a Mendelian fashion in these families. Alleles from heterozygous male-parents, however, were inherited in two different ways: (i) in a Mendelian fashion and (ii) in a non-Mendelian fashion, where males passed to their offspring only one of their two alleles, that is, 100% nonrandom transmission. In male body lice, where there was non-Mendelian inheritance, the paternally inherited set of alleles was eliminated. We interpret this pattern of inheritance as evidence for extreme transmission ratio distortion of paternal alleles in this species.
Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division
4283Wu, GMH, L. P.; Han, Z. M.; Gao, S. R.; Latham, K. E.; de Villena, F. P. M.; Sapienza, C., Genetics, 170:327-334. 2005-01-21 00:00:00.
We have observed maternal transmission ratio distortion (TRD) in favor of DDK alleles at the Ovum mutant (Om) locus on mouse chromosome I I among the offspring of (C57BL/6 X DDK) F, females and C57BL/6 males. Although significant lethality occurs in this backcross (similar to 50%), differences in the level of TRD found in recombinant vs. nonrecombinant chromosomes among offspring argue that TRD is due to nonrandom segregation of chromatids at the second meiotic division, i.e., true meiotic drive. We tested this hypothesis directly, by determining the centromere and Om genotypes of individual chromatids in zygote stage embryos. We found similar levels of TRD in favor of DDK alleles at Om in the female pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In those embryos for which complete dyads have been reconstructed, TRD was present only in those inheriting heteromorphic dyads. These results demonstrate that meiotic drive occurs at MII and that preferential death of one genotypic class of embryo does not play a large role in the TRD.
Evidence of susceptibility and resistance to cryptic X-linked meiotic drive in natural populations of Drosophila melanogaster
4281Reed, FAR, R. G.; Aquadro, C. F., Evolution, 59:1280-1291. 2005-01-19 00:00:00.
There is mounting evidence consistent with a general role of positive selection acting on the Drosophila melanogaster X-chromosome. However, this positive selection need not necessarily arise from forces that are adaptive to the organism. Nonadaptive meiotic drive may exist on the X-chromosome and contribute to forces of selection. Females from a reference D. melanogaster line, containing the X-linked marker white, were crossed to males from 49 isofemale lines established from seven African and five non-African natural populations to detect naturally occurring meiotic drive. Several lines exhibited a departure from expected Mendelian transmission of X-chromosomes to the third generation (F-2) offspring, particularly those from hybrid African male parents. F2 viability was not correlated with skewed chromosomal inheritance. However, a significant difference in viability between cosmopolitan and tropical African crosses was observed. Recombination analysis supports the presence of a male-acting meiotic drive element near the centromeric region of the X-chromosome and putative recessive autosomal drive suppression. There is also evidence of another female-acting drive element linked to white. The possible role meiotic drive may contribute in shaping levels of genetic variation in D. melanogaster, and additional ways to test this hypothesis are discussed.
Segregation distortion in hybrids between the Bogota and USA subspecies of Drosophila pseudoobscura
4279Orr, HAI, S., Genetics, 169:671-682. 2005-01-17 00:00:00.
We show that, contrary to claims in the literature, "sterile" males resulting from the cross of the Bogota and USA subspecies of Drosophila pseudoobscura are weakly fertile. Surprisingly, these hybrid males produce almost all daughters when crossed to females of any genotype (pure Bogota, pure USA, hybrid F-1). Several lines of evidence suggest that this sex ratio distortion is caused by sex chromosome segregation distortion in hybrid males. We genetically analyze this normally cryptic segregation distortion and show that it involves several regions of the Bogota X chromosome that show strong epistatic interactions with each other. We further show that segregation distortion is normally masked within the Bogota subspecies by amosomal suppressors. Our analysis shows that the genetic basis of hybrid segregation distortion is similar to that of hybrid male sterility between the same subspecies. Indeed the severity of segregation distortion is correlated with the severity of sterility among hybrids. We discuss the possibility that hybrid sterility in this paradigmatic case of incipient speciation is caused by segregation distortion.
Meiotic drive at the Om locus in wild-derived inbred mouse strains
4277Kim, KT, S.; Howard, I. B.; Bell, T. A.; Doherty, H. E.; Ideraabdullah, F.; Detwiler, D. A.; De Villena, F. P. M., Biological Journal of the Linnean Society, 84:487-492. 2005-01-15 00:00:00.
Meiotic drive is an evolutionary force in which natural selection is uncoupled from organismal fitness. Recently, it has been proposed that meiotic drive and genetic drift represent major forces in the evolution of the mammalian karyotype. Meiotic drive involves two types of genetic elements, Responders and Distorters, the latter being required to induce transmission ratio distortion at the former. We have previously described the Om meiotic drive system in mouse chromosome 11. To investigate the natural history of this drive system we have characterized the alleles present at the distorter in wild-derived inbred strains. Our analysis of transmission of maternal alleles in both classical and wild-derived inbred strains indicated that driving alleles are found at high frequency in natural populations and that the existence of driving alleles predates the split between the Mus spicilegus and M. musculus lineages. (c) 2005 The Linnean Society of London.
A novel meiotic drive locus almost completely distorts segregation in Mimulus (monkeyflower) hybrids
4274Fishman, LW, J. H., Genetics, 169:347-353. 2005-01-12 00:00:00.
We report the discovery, mapping, and characterization of a meiotic drive locus (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus. Only 1% of F-2 hybrids were M. nasutus homozygotes at the marker most tightly linked to D. We used a set of reciprocal backcrosses to distinguish among male-specific, female-specific, and zygote-specific sources of transmission ratio distortion. Transmission was severely distorted only when the heterozygous F, acted as the female parent in crosses to either parental species, ruling out pollen competition and zygote mortality as potential sources of drive. After four generations of backcrossing to M. nasutus, nearly isogenic lines were still >90% heterozygous at markers linked to D, suggesting that heterozygosity at the drive locus alone is sufficient for nonrandom transmission. A lack of dramatic female fitness costs in these lines rules out alternatives involving ovule or seed mortality and points to a truly meiotic mechanism of drive. The strength and direction of drive in this system is consistent with population genetic theory of selfish element evolution under different mating systems. These results are the first empirical demonstration of the strong female-specific drive predicted by new models of selfish centromere turnover.
Evolution of autosomal suppression of the sex-ratio trait in Drosophila
4302Vaz, SCC, A. B., Genetics, 166:265-277. 2004-01-20 00:00:00.
The sex-ratio trait is the production of female-biased progenies due to X-linked meiotic drive in males of several Drosophila species. The driving X chromosome (called SR) is not fixed due to at least two stabilizing factors: natural selection (favoring ST, the nondriving standard X) and drive suppression by either Y-linked or autosomal genes. The evolution of autosomal suppression is explained by Fisher's principle, a mechanism of natural selectin that leads to equal proportion of males and females in a sexually reproducing population. In fact, sex-ratio expression is partially suppressed by autosomal genes in at least three Drosophila species. The population genetics of this system is not completely understood. In this article we develop a mathematical model for the evolution of autosomal suppressors of SR (sup alleles) and show that: (i) an autosomal suppressor cannot invade when SR is very deleterious in males (c < 1/3, where c is the fitness of SR/Y males); (ii) "SR/ST, sup/+" polymorphisms occur when SR is partially deleterious (similar to0.3 < c < 1); while (iii) SR neutrality (c = 1) results in sup fixation and thus in total abolishment of drive. So, surprisingly, as long as there is any selection against SR/Y males, neutral autosomal suppressors will not be fixed. In that case, when a polymorphic equilibrium exists, the average female proportion in SR/Y males' progeny is given approximately by (ac + 1 - a + roota(9) ( c + 1 )(2) + 1 - 4ac)/4ac, where a is the fitness of SR/ST females.
B chromosomes and genome size in flowering plants
4301Trivers, RB, A.; Palestis, B. G., Genome, 47:1-8. 2004-01-19 00:00:00.
B chromosomes are extra chromosomes found in some, but not all, individuals within a species, often maintained by giving themselves an advantage in transmission, i.e. they drive. Here we show that the presence of B chromosomes correlates to and varies strongly and positively with total genome size (excluding the Bs and corrected for ploidy) both at a global level and via a comparison of independent taxonomic contrasts. B chromosomes are largely absent from species with small genomes; however, species with large genomes are studied more frequently than species with small genomes and Bs are more likely to be reported in well-studied species. We controlled for intensity of study using logistic regression. This regression analysis also included effects of degree of outbreeding, which is positively associated with Bs and genome size, and chromosome number, which is negatively associated with Bs and genome size, as well as variable ploidy (more than one ploidy level in a species). Genome size, breeding system and chromosome number all contribute independently to the distribution of B chromosomes, while variable ploidy does not have a significant effect. The genome size correlates are consistent with reduced selection against extra DNA in species with large genomes and with increased generation of B sequences from large A genomes.
Rapid suppression of drive for a parasitic B chromosome
4298Perfectti, FC, J. M.; Mesa, J. A.; Cabrero, J.; Bakkali, M.; Lopez-Leon, M. D.; Camacho, J. P. M., Cytogenetic and Genome Research, 106:338-343. 2004-01-16 00:00:00.
The persistence of parasitic B chromosomes in natural populations depends on both B ability to drive and host response to counteracting it. In the grasshopper Eyprepocnemis plorans, the B-24 chromosome is the most widespread B chromosome variant in the Torrox area ( Malaga, Spain). Its evolutionary success, replacing its ancestral neutralized B variant, B-2, was based on meiotic drive in females, as we showed in a sample caught in 1992. In females collected six years later, mean B-24 transmission ratio (k(B)) was 0.523, implying a very rapid decrease from the 0.696 observed in 1992. This shows that B-24 neutralization is running very fast and suggests that it might most likely be based on a single gene of major effect. Copyright (C) 2004 S. Karger AG, Basel.
B chromosomes are more frequent in mammals with acrocentric karyotypes: support for the theory of centromeric drive
4296Palestis, BGB, A.; Jones, R. N.; Trivers, R., Proceedings of the Royal Society B-Biological Sciences, 271:S22-S24. 2004-01-14 00:00:00.
The chromosomes of mammals tend to be either mostly acrocentric (having one long arm) or mostly bi-armed, with few species having intermediate karyotypes. The theory of centromeric drive suggests that this observation reflects a bias during female meiosis, favouring either more centromeres or fewer, and that the direction of this bias changes frequently over evolutionary time. B chromosomes are selfish genetic elements found in some individuals within some species. B chromosomes are often harmful, but persist because they drive (i.e. they are transmitted more frequently than expected). We predicted that species with mainly acrocentric chromosomes would be more likely to harbour B chromosomes than those with mainly bi-armed chromosomes, because female meiosis would favour more centromeres over fewer in species with one-armed chromosomes. Our results show that B chromosomes are indeed more common in species with acrocentric chromosomes, across all mammals, among rodents, among non-rodents and in a test of independent taxonomic contrasts. These results provide independent evidence supporting the theory of centromeric drive and also help to explain the distribution of selfish DNA across species. In addition, we demonstrate an association between the shape of the B chromosomes and the shape of the typical ('A') chromosomes.
Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera : Culicidae)
4295Mori, AC, D. D.; Graham, D. H.; Severson, D. W., Journal of Medical Entomology, 41:1027-1033. 2004-01-13 00:00:00.
We have initiated efforts to determine the molecular basis for the M-D meiotic drive system in the mosquito, Aedes aegypti. The effect of the M-D gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M-D system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M-D gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible in m(s) females result in progeny with highly biased sex ratios, wherein only approximate to14.7% females are produced. We discuss the potential for identifying M-D candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M-D and insensitive m(i) alleles are likely segregating.
Meiotic drive and sex chromosome cycling
4291Hall, DW, Evolution, 58:925-931. 2004-01-09 00:00:00.
Sex-linked meiotic drive is found in a broad variety of taxa, including insects, birds, and mammals. In populations of some species, we see four types of sex chromosomes segregating: normal and driving X chromosomes and susceptible and resistant Y chromosomes. A theoretical analysis shows that a stable four-chromosome equilibria is a more common outcome in these systems than previously recognized. Cycling of sex chromosome frequencies and associated changes in the sex ratio are other predicted outcomes. The absence of cycling in nature may be due to migration among populations.
Identification of quantitative trait loci affecting sex determination in the eastern treehole mosquito (Ochlerotatus triseriatus)
4290Graham, DHH, J. L.; Black, W. C., Journal of Heredity, 95:35-45. 2004-01-08 00:00:00.
Laboratory colonies of the eastern treehole mosquito (Ochlerotatus triseriatus (Say)) exhibit a consistent female-biased sex ratio. This is unusual among mosquito species, in which heritable sex ratio distortion is usually male biased and mediated by meiotic drive. Quantitative trait loci (QTL) affecting sex were mapped in an F-1 intercross to better understand the genetics underlying this female bias. In P-1 and F-1 parents and in 146 F-2 individuals with a female-biased sex ratio (106 females:40 males), regions of seven cDNA loci were analyzed with single-strand conformation polymorphism (SSCP) analysis to identify and orient linkage groups. Genotypes were also scored at 73 random amplified polymorphic DNA (RAPD)-SSCP loci. In addition to the sex locus, at least four QTL affecting sex determination were detected with interval mapping on linkage groups I and II. Alleles at the sex locus cumulatively accounted for approximately 61-77% of the genetic variance in sex. Alleles at QTL adjacent to the sex locus and at a QTL on the opposite end of linkage group I increased the proportion of females, but alleles at a QTL on linkage group I and a second QTL on linkage group II increased the proportion of males. The female-biased sex ratio observed in laboratory colonies of O. triseriatus is most easily explained by the existence of multiple female biased distorter loci, as have been observed in other Diptera.
Sperm survival in female stalk-eyed flies depends on seminal fluid and meiotic drive
4289Fry, CLW, G. S., Evolution, 58:1622-1626. 2004-01-07 00:00:00.
Sperm competition is common in many insect species; however, the mechanisms underlying differences in sperm precedence are not well understood. In the stalk-eyed fly, Cyrtodiopsis whitei (Diptera, Diopsidae), sperm precedence is influenced by the presence of sex chromosome meiotic drive. When drive-carrying males compete with non-driving males for fertilizations within a female, the number of progeny sired by drive males is significantly fewer than predicted by sperm mixing alone. Thus, drive males apparently suffer not only a reduction in the number of viable sperm produced, but also a reduction in sperm competitive ability. In this study, we manipulated the amount and source of seminal fluid and sperm received by females by interrupting copulations before sperm, but after seminal fluid, was transferred. We find that seminal fluid from another male influences the number of progeny sired by a drive-carrying male when both males mate with the same female. Sperm viability staining reveals that sperm from drive males are incapacitated by seminal fluid from other males within the female reproductive tract. These results suggest that multiple mating by females enables seminal fluid products to interact differentially with sperm and may reduce the transmission advantage of the drive chromosome.
To what extent do different types of sex ratio distorters interfere?
4288Engelstadter, JM, H.; Hurst, G. D. D., Evolution, 58:2382-2386. 2004-01-06 00:00:00.
Within the Diptera, two different selfish genetic elements are known to cause the production of female-biased sex ratios: maternally inherited bacteria that kill male zygotes (male-killers), and X chromosomes causing the degeneration of Y-bearing sperm in males (meiotic drive). We here develop a mathematical model for the dynamics of these two sex-ratio distorters where they co-occur. We show that X chromosome meiotic drive elements can be expected to substantially lower the equilibrium frequency of male-killers and can even lead to their extinction. Conversely, male-killers can also decrease the equilibrium frequency of X drivers and cause their extinction. Thus, we predict that there will be some complementarity in the incidence of X chromosome meiotic drive and male-killing in natural populations, with a lower than expected number of species bearing both elements.
Analysis of two additional loci in Neurospora crassa related to Spore killer-2
4319Turner, BC, Fungal Genetics and Biology, 39:142-150. 2003-01-17 00:00:00.
Two new loci found in one strain of Neurospora crassa (P2604) collected in Malaya are related to the meiotic drive system Spore killer Sk-2. Sk-2 was found in Neurospora intermedia and introgressed into N. crassa. P2604 showed high resistance to killing when crossed to Sk-2. This resistance was found to be linked to, but not allelic to, resistance locus r(Sk-2) on LGIIIL. Analysis showed that the high resistance phenotype of P2604 requires resistance alleles at two different loci on LGIIIR. Strains carrying a resistance allele at only the proximal or the distal locus, respectively, were obtained and intercrossed. Highly resistant strains were obtained by rejoining the two genes. The proximal locus alone confers a low level of resistance. This locus was named pr(Sk-2) for partial resistance to Sk-2. The distal locus was named mod(pr) because its only known phenotype is to modify pr(Sk-2). (C) 2003 Elsevier Science (USA). All rights reserved.
Common features of segregation distortion in plants and animals
4318Taylor, DRI, P. K., Genetica, 117:27-35. 2003-01-16 00:00:00.
Segregation distortion is increasingly recognized as a potentially powerful evolutionary force. This runs counter to the perception that non-Mendelian genes are rare genetic curiosities, a view that seems to be supported by the near ubiquity of the Mendelian system of inheritance. There are several reasons why segregation distortion may be more important than is evidenced by known empirical examples. One possibility is that the types of segregation distorters we have found are only a subset of a broader range of non-Mendelian systems, many of which go undetected. In this paper, we review what is known about the sex-linked meiotic drive system in the plant, Silene latifolia, and present some data on the mechanism of segregation distortion. We outline the general features that segregation distorters in plants and animals have in common. In some cases, such as the paucity of systems that directly alter meiotic segregation, there are likely to be inherent constraints on the range of systems that can possibly occur. Other generalities, however, support the notion that many forms of meiotic drive are possible, and that the known examples of segregation distortion are likely to be only subset of those that can possibly occur. Non-Mendelian genes may therefore have greater evolutionary importance than their current abundance in nature would suggest.
Meiotic drive – Bickering genes shape evolution – Not all genes follow the rules of inheritance; now researchers are discovering how organisms adapt to the troublemakers
4316Pennisi, E, Science, 301:1837-1839. 2003-01-14 00:00:00.
Reproduction is supposed to be an equal opportunity event. Consider humans: In developing sperm, the sex chromosomes sort 50:50 such that half the sperm carry the male-defining Y chromosome and the rest sport an X. Only the randomness of fertilization leads to families of nine girls and no boys, for example. The same supposedly holds true for the rest of the genome. But in humans, flies, mice, and perhaps many other organisms, guerrilla warfare within the genome sometimes pits one element against another. This often takes on the appearance of a battle between the sexes, but it is really a fight between genes. In this struggle, typically one or more of the X chromosome’s genes strike out against the Y’s genes. Genes on other chromosomes also can get caught up in this struggle, causing an escalating arms race.
The aging effect in the segregation distorter system of Drosophila melanogaster
4315Oh, SCN, J. G., Korean Journal of Genetics, 25:237-242. 2003-01-13 00:00:00.
The SD/SD+ heterozygous male of Drosophila melanogaster transmits the SD second chromosome to its progeny in excess of the Mendelian frequency of 0.5. The k value is defined as the frequency of the SD chromosome recovered among progeny from such a male. This value has been shown to be affected by the age of the male parent: it tends to decrease with increasing age of the parental male, and this aging effect is heritable. The present study indicates that there is a genotypic condition in which the effect of male age is to increase the k value, and this increase is heritable. Thus, a heritable aging effect can occur in both increasing and decreasing the k values, depending upon the genotypes.
Closing the (Ran)GAP on segregation distortion in Drosophila
4313Kusano, AS, C.; Chan, H. Y. E.; Ganetzky, B., Bioessays, 25:108-115. 2003-01-11 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to induced dysfunction of SD+ spermatids. Since its discovery in 1956, SD and its mode of action have baffled biologists. Recently, substantial progress has been made in elucidating this puzzle. Sd, the primary gene responsible for distortion encodes a mutant RanGAP, a key protein in the Ran signaling pathway required for nuclear transport and other nuclear functions. The mutant protein is enzymatically active but mislocalized to nuclei, which apparently disrupts Ran signaling by reducing intranuclear Ran-GTP levels. Some evidence suggests that a defect in nuclear transport may be the main cause of sperm dysfunction. Although important questions remain, the basic mechanism of distortion is now understood sufficiently well that specific hypotheses can be formulated and tested. This previously mysterious genetic system may now offer unique insights into novel aspects of regulation by Ran. (C) 2003 Wiley Periodicals, Inc.
Responder (Rsp) alleles in the Segregation Distorter (SD) system of meiotic drive in Drosophila may represent a complex family of satellite repeat sequences
4311Houtchens, KL, T. W., Genetica, 117:291-302. 2003-01-09 00:00:00.
In D. melanogaster males carrying Segregation Distorter (SD) second chromosomes, sperm receiving sensitive alleles of the Responder (Rsp) locus are subject to high rates of dysfunction. The Rsp region is located in 2R immediately adjacent to the centromere in heterochromatic band 39, and covers roughly 600 kb of material, of which approximately 85 kb is comprised of several hundred copies of a 240-bp satellite DNA sequence. Cytological observations as well as molecular analysis of rearrangements which bisect h39 indicate that sensitivity of the Rsp target to SD action is also subdivisible, and sensitivities of the component pieces appear to be correlated with copy number of the 240 bp repeat. In an attempt to examine possible higher order sequence structure for these blocks, PCR using single primers derived from a canonical repeat was used to identify potential reversals of direction of tandem arrays; that is, head-to-head or tail-to-tail junctions. Surprisingly, for two different Rsp alleles, only a single such reversal product for each was identified, differing in size and sequence between alleles. Sequencing of PCR products identified diverged copies of the canonical repeats that would not have been found using the levels of DNA stringency employed in earlier studies. Examination of Southern digests and slot-blots for DNA quantification indicates that adding the estimated numbers of such diverged copies to the canonical repeat copies discovered earlier is potentially sufficient to account for the entire 600 kb Rsp region. This adds strength to the hypothesis that this extended family of repeats is in fact the target of SD-mediated sperm dysfunction. Implications of these results for understanding the evolution of repetitive DNA are also discussed.
Four loci on abnormal chromosome 10 contribute to meiotic drive in maize
4309Hiatt, END, R. K., Genetics, 164:699-709. 2003-01-07 00:00:00.
We provide a genetic analysis of the meiotic drive system on maize abnormal chromosome 10 (Ab10) that causes preferential segregation of specific chromosomal regions to the reproductive megaspore. The data indicate that at least four chromosomal regions contribute to meiotic drive, each providing distinct functions that can be differentiated from each other genetically and/or phenotypically. Previous reports established that meiotic drive requires neocentromere activity at specific tandem repeat arrays (knobs) and that two regions on Ab10 are involved in trans-activating neocentromeres. Here we confirm and extend data suggesting that only one of the neocentromere-activating regions is sufficient to move many knobs. We also confirm the localization of a locus/loci on Ab10, thought to be a prerequisite for meiotic drive, which promotes recombination in structural heterozygotes. In addition, we identified two new and independent functions required for meiotic drive. One was identified through the characterization of a deletion derivative of Ab10 [Df(L)] and another as a newly identified meiotic drive mutation (suppressor Of meiotic drive 3). In the absence of either function, meiotic drive is abolished but neocentromere activity and the recombination effect typical of Ab10 are unaffected. These results demonstrate that neocentromere activity and increased recombination are not the only events required for meiotic drive.
The meiotic drive system on maize abnormal chromosome 10 contains few essential genes
4308Hiatt, END, R. K., Genetica, 117:67-76. 2003-01-06 00:00:00.
In maize, a distal portion of abnormal chromosome 10 (Ab10) causes the meiotic drive of itself as well as many unlinked heterochromatic regions known as knobs. The Ab10 drive system, which encodes trans- as well as cis-acting components, occupies a large region of chromosome 10L equivalent to similar to3% of the genome. Here we describe five new structural mutations of Ab10 (five deletions and a duplication) that arose from a screen for meiotic drive mutants. The high frequency of breakage events, detected both genetically and cytologically, suggest that the chromosome may be especially unstable. Very large deletions within the drive system are female-transmissible and plants homozygous for deficiencies lacking much of this interval can be grown to maturity. The data suggest that few genes required for normal growth and development lie within the portion of Ab10 responsible for meiotic drive. These and other published data suggest that meiotic drive systems tend to evolve in gene-sparse or otherwise information-poor regions of the genome where they are less likely to negatively affect individual fitness.
Sexual transmission of the Het-s prion leads to meiotic drive in Poldospora anserina
4307Dalstra, HJPS, K.; Debets, A. J. M.; Saupe, S. J.; Hoekstra, R. F., Proceedings of the National Academy of Sciences of the United States of America, 100:6616-6621. 2003-01-05 00:00:00.
In the filamentous fungus Podospora anserina, two phenomena are associated with polymorphism at the het-s locus, vegetative incompatibility and ascospore abortion. Two het-s alleles occur naturally, het-s and het-S. The het-s encoded protein is a prion propagating as a self-perpetuating amyloid aggregate. When prion-infected [Het-s] hyphae fuse with [Het-S] hyphae, the resulting heterokaryotic cells necrotize. [Het-s] and [Het-S] strains are sexually compatible. When, however, a female [Het-s] crosses with [Het-S], a significant percentage of het-S spores abort, in a way similar to spore killing in Neurospora and Podospora. We report here that sexual transmission of the [Het-s] prion after nonisogamous mating in the reproductive cycle of Podospora is responsible for the killing of het-S spores. Progeny of crosses between isogenic strains with distinct wild-type or introduced, ectopic het-s/S alleles were cytologically and genetically analyzed. The effect of het-s/S overexpression, ectopic het-s/S expression, absence of het-s expression, loss of [Het-s] prion infection, and the distribution patterns of HET-s/S-GFP proteins were categorized during meiosis and ascospore formation. This study unveiled a het-S spore-killing system that is governed by dosage of and interaction between the [Het-s] prion and the HET-S protein. Due to this property of the [Het-s] prion, the het-s allele acts as a meiotic drive element favoring maintenance of the prion-forming allele in natural populations.
Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot
4322Jeffreys, AJN, R., Nature Genetics, 31:267-271. 2002-01-20 00:00:00.
Human DNA diversity arises ultimately from germline mutation that creates new haplotypes that can be reshuffled by meiotic recombination. Reciprocal crossover generates recombinant haplotypes but should not influence the frequencies of alleles in a population. We demonstrate crossover asymmetry at a recombination hot spot in the major histocompatibility complex(1), whereby reciprocal exchanges in sperm map to different locations in the hot spot. We identify a single-nucleotide polymorphism at the center of the hot spot and show that, when heterozygous, it seems sufficient to cause this asymmetry, apparently by influencing the efficiency of highly localized crossover initiation. As a consequence, crossovers in heterozygotes are accompanied by biased gene conversion, most likely occurring by gap repair(2), that can also affect nearby polymorphisms through repair of an extended gap. The result is substantial over-transmission of the recombination-suppressing allele and neighboring markers to crossover products. Computer simulations show that this meiotic drive, although weak at the population level, is sufficient to favor eventual fixation of the recombination-suppressing variant. These findings provide an explanation for the relatively uniform widths of human crossover hot spots and suggest that hot spots may be generally prone to extinction by meiotic drive(3).
X chromosome effect on maternal recombination and meiotic drive in the mouse
4321de la Casa-Esperon, EL-O, J. C.; de Villena, F. P. M.; Briscoe, T. L.; Malette, J. M.; Vaughan, J. E.; Morgan, K.; Sapienza, C., Genetics, 161:1651-1659. 2002-01-19 00:00:00.
We observed that maternal meiotic drive favoring the inheritance of DDK alleles at the Om locus on mouse chromosome 11 was correlated with the X chromosome inactivation phenotype of (C57BL/6Pgk1(a) X DDK)F-1 mothers. The basis for this unexpected observation appears to lie in the well-documented effect of recombination on meiotic drive that results from nonrandom segregation of chromosomes. Our analysis of genome-wide levels of meiotic recombination in females that vary in their X-inactivation phenotype indicates that an allelic difference at an X-linked locus is responsible for modulating levels of recombination in oocytes.
Sperm competition and the dynamics of X chromosome drive: Stability and extinction
4326Taylor, JEJ, J., Genetics, 160:1721-1731. 2002-01-04 00:00:00.
Several empirical studies of sperm competition in populations polymorphic for a driving X chromosome have revealed that Sex-ratio males (those carrying a driving X) are at a disadvantage relative to Standard males. Because the frequency of the driving X chromosome determines the population-level sex ratio and thus alters male and female mating rates, the evolutionary consequences of sperm competition for sex chromosome meiotic drive are subtle. As the SR allele increases in frequency, the ratio of females to males also increases, causing an increase in the male mating rate and a decrease in the female mating rate. While the former change may exacerbate the disadvantage of Sex-ratio males during sperm competition, the latter change decreases the incidence of sperm competition within the population. We analyze a model of the effects of sperm competition on a driving X chromosome and show that these opposing trends in male and female mating rates call result in two coexisting locally stable equlibria, one corresponding to a balanced polymorphism of the SR and ST alleles and the second to fixation of the ST allele. Stochastic fluctuations of either the Population sex ratio or the SR frequency call then drive the population away from the balanced polymorphism and into the basin of attraction for the second equilibrium, resulting in fixation of the SR allele and extinction of the population.
Segregation distortion induced by wild-type RanGAP in Drosophila
4324Kusano, AS, C.; Ganetzky, B., Proceedings of the National Academy of Sciences of the United States of America, 99:6866-6870. 2002-01-02 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to the induced dysfunction of SD+ spermatids. The key distorter locus, Sid, is a dominant neomorphic allele encoding a truncated, but enzymatically active, RanGAP (RanGTPase-activating protein) whose nuclear mislocalization underlies distortion by disrupting the Ran signaling pathway. Here, we show that even wild-type RanGAP can cause segregation distortion when it is overexpressed in the male germ line or when the gene dosage of a particular modifier locus is increased. Both manipulations result in substantial nuclear accumulation of RanGAP. Distortion can be suppressed by overexpression of Ran or Ran guanine nucleotide exchange factor (RanGEF) in the male germ line, indicating that the primary consequence of nuclear mislocalization of RanGAP is reduction of intranuclear RanGTP levels. These results prove that segregation distortion does not depend on any unique properties of the mutant RanGAP encoded by Sid and provide a unifying explanation for the occurrence of distortion in a variety of experimental situations.
Sperm development, age and sex chromosome meiotic drive in the stalk-eyed fly, Cyrtodiopsis whitei
4337Wilkinson, GSS, M. I., Heredity, 87:17-24. 2001-01-15 00:00:00.
The cytological basis of X chromosome meiotic drive or sex ratio (SR) has been reported for several species of Drosophila but not for other species. Here we describe how sperm development in the stalk-eyed fly, Cyrtodiopsis whitei, influences progeny sex proportion, in order to determine if a common developmental mechanism could cause meiotic drive in these distantly related taxa. Because age has been found to affect the degree of segregation distortion in some Drosophila, we tested flies from six to 26 weeks of age. We find that spermatocyst bundles in SR males frequently contain incompletely elongated spermatid nuclei independently of male age. Older males have, however, more spermatocyst bundles in their testes than younger males. Abnormal spermatid elongation affects male fertility since SR males produce 74% as many progeny per week as ST males. The proportion of spermatocyst bundles with improperly elongated spermatid nuclei explains 71% of the variation in progeny sex proportion. After reviewing the literature on sperm development and meiotic drive, we conclude that the cytological basis of meiotic drive in diopsids closely resembles Drosophila. Across species in both groups, the production of fertile males is associated with less than half of all spermatids not elongating normally in a spermatocyst bundle. We discuss the possibility that frequency-dependent selection on male fertility could stabilize the drive polymorphism in these unusual flies.
Meiotic drive alters sperm competitive ability in stalk-eyed flies
4336Wilkinson, GSF, C. L., Proceedings of the Royal Society B-Biological Sciences, 268:2559-2564. 2001-01-14 00:00:00.
Meiotic drive results when sperm carrying a driving chromosome preferentially survive development. Meiotic drive should therefore influence sperm competition because drive males produce fewer sperm than non-drive males. Whether meiotic drive also influences the competitive ability of sperm after ejaculation is unknown. Here we report the results from reciprocal crosses that are designed for estimating the sperm precedence of male stalk-eyed flies (Cyrtodiopsis whitei) with or without X-linked meiotic drive. We find that nearly half of all sex-ratio males, as compared with 14 % of non-sex-ratio males, fail to produce young in a reciprocal cross. Furthermore, the proportion of progeny sired by a sex-ratio male in a female jointly inseminated by a non-sex-ratio male was less than expected from the number of sperm transferred. These effects are not due to differential sperm storage by females because, after a single mating with a sex-ratio male, all females stored sperm and because two sex-ratio males share paternity after jointly mating with a female. In addition to demonstrating a new mechanism of sperm competition, these results provide insight into the maintenance of sex-ratio polymorphisms. Sex-ratio males have less than one-half the fertility of non-sex-ratio males, as is required in order for frequency-dependent selection on males to produce a stable sex-ratio polymorphism.
Selection and segregation distortion in a sex-differentiated population
4335Weissing, FJvB, M., Theoretical Population Biology, 60:327-341. 2001-01-13 00:00:00.
We extend the classical model for selection at an autosomal locus in a sex-differentiated population to include segregation distortion. The equations remain the same, but the fitness parameters are interpreted differently and refer to alleles instead of genotypes. We derive conditions for internal and external stability of the equilibria, i.e., stability with respect to perturbations of alleles that are already present at equilibrium and stability with respect to invasion attempts by newly arising alleles. We show that, in a sex-differentiated population, external stability of an equilibrium can be judged on the basis of Shaw-Mohler criteria. Throughout, we compare the situation in populations with and without sex differentiation. Interestingly, internal stability is more difficult to achieve in a population without sex differentiation than in a population in which selection and segregation distortion are restricted to one sex. In a companion paper we show how the general results of the present paper can lead to new insights into specific systems such as the t complex of the house mouse. (C) 2001 Elsevier Science.
Competition at the Mouse t Complex: Rare Alleles Are Inherently Favored
4334van Boven, MW, Franz J., Theoretical Population Biology, 60:343-358. 2001-01-12 00:00:00.
We investigate the competition between alleles at a segregation distorter locus. The focus is on the invasion prospects of rare mutant distorter alleles in a population in which a wildtype and a resident distorter allele are present. The parameters are chosen to reflect the situation at the t complex of the house mouse, one of the best-studied examples of segregation distortion. By analyzing the invasion chances of rare alleles, we provide an analytical justification of earlier simulation results. We show that a new distorter allele can successfully invade even if it is inferior both at the gamete and at the individual level. In fact, newly arising distorter alleles have an inherent rareness advantage if their negative fitness consequences are restricted to homozygous condition. Likewise, rare mutant wildtype alleles may often invade even if their viability or fertility is reduced. As a consequence, the competition between alleles at a segregation distorter locus should lead to a high degree of polymorphism. We discuss the implications of this conclusion for the t complex of the house mouse and for the evolutionary stability of “honest” Mendelian segregation.
Sex-ratio segregation distortion associated with reproductive isolation in Drosophila
4333Tao, YH, D. L.; Laurie, C. C., Proceedings of the National Academy of Sciences of the United States of America, 98:13183-13188. 2001-01-11 00:00:00.
Sex-ratio distortion is the most common form of non-Mendelian segregation observed in natural populations. It may occur even more frequently than direct observations suggest, because the dysgenic population consequences of a biased sex ratio are expected to result in the rapid evolution of suppressors, resulting in suppressed or "cryptic" segregation distortion. Here we report evidence for cryptic sex-ratio distortion that was discovered by introgressing segments of the genome of Drosophila mauritiana into the genome of Drosophila simulans. The autosomal suppressor of sex-ratio distortion, which is also associated with a reduction in hybrid male fertility, has been genetically localized to a region smaller than 80-kb pairs in chromosome 3.
An unusual sex-determination system in South American field mice (genus Akodon): The role of mutation, selection, and meiotic drive in maintaining XY females
4330Hoekstra, HEH, J. M., Evolution, 55:190-197. 2001-01-08 00:00:00.
The mechanism of sex determination in mammals appears highly conserved: the presence of a Y chromosome triggers the male developmental pathway, whereas the absence of a Y chromosome results in a default female phenotype. However, if the Y chromosome fails to initiate the male pathway (referred to as Y*), XY* females can result, as is the case in several species of South American field mice (genus Akodon). The breeding genetics in this system inherently select against the Y* chromosome such that the frequency of XY* females should decrease rapidly to very low frequencies. However, in natural populations of Akodon, XY* females persist at substantial frequencies; for example, 10% of females are XY* in A. azarae and 30% in A. boliviensis. We develop a mathematical model that considers the potential roles of three evolutionary forces in maintaining XY* females: Y-to-Y* chromosome transitions (mu ration), chromosome segregation distortion (meiotic drive), and differential fecundity (selection). We then test the predictions of our model using data from breeding colonies of A. azarae. We conclude that any single force is inadequate to maintain XY* females. However, a combination of segregation bias of the male and female Y chromosomes during spermatogenesis/oogenesis and increased fecundity in XY* females could account for the observed frequencies of XY* females.
Nonrandom segregation during meiosis: the unfairness of females
4328de Villena, FPMS, C., Mammalian Genome, 12:331-339. 2001-01-06 00:00:00.
Most geneticists assume that chromosome segregation during meiosis is Mendelian (i.e., each allele at each locus is represented equally in the gametes). The great majority of reports that discuss non-Mendelian transmission have focused on systems of gametic selection, such as the mouse t-haplotype and Segregation distorter in Drosophila, or on systems in which post-fertilization selection takes place, Because the segregation of chromosomes in such systems is Mendelian and unequal representation of alleles among offspring is achieved through gamete dysfunction or embryonic death, there is a common perception that true disturbances in the randomness of chromosome segregation are rare and of limited biological significance. In this review we summarize data on nonrandom segregation in a wide variety of genetic systems. Despite apparent differences between some systems, the basic requirements for nonrandom segregation can be deduced from their shared characteristics: i) asymmetrical meiotic division(s); ii) functional asymmetry of the meiotic spindle poles: and iii) functional heterozygosity at a locus that mediates attachment of a chromosome to the spindle. The frequency with which all three of these requirements al e fulfilled in natural populations is an known, but our analyses indicate that nonrandom segregation occurs with sufficient frequency during female meiosis, and in exceptional cases of male meiosis, that it has important biological, clinical, and evolutionary consequences.
Heritability of the maternal meiotic drive system linked to Om and high-resolution mapping of the Responder locus in mouse
4339de Villena, FPMdlC-E, E.; Williams, J. W.; Malette, J. M.; Rosa, M.; Sapienza, C., Genetics, 155:283-289. 2000-01-17 00:00:00.
Matings between (C57BL/6 X DDK)F-1 females and C57BL/6 males result in a significant excess of offspring inheriting maternal DDK alleles in the central region of mouse chromosome 11 due to meiotic drive at the second meiotic division. We have shown previously that the locus subject to selection is in the vicinity of D11Mit66, a marker closely linked to the Om locus that controls the preimplantation embryolethal phenotype known as the "DDK syndrome." We have also shown that observation of meiotic drive in this system depends upon tl-le genotype of the sire. Here we show that females that are heterozygous at Om retain the meiotic drive phenotype and define a 0.32-cM candidate interval for the Responder locus in this drive system. In addition, analysis of the inheritance of alleles at Om among the offspring of F-1 intercrosses indicates that the effect of the sire is determined by the sperm genotype at Om or a locus linked to Om.
Spore-killing meiotic drive factors in a natural population of the fungus Podospora anserina
4348van der Gaag, MD, A. J. M.; Oosterhof, J.; Slakhorst, M.; Thijssen, Jagm; Hoekstra, R. F., Genetics, 156:593-605. 2000-01-06 00:00:00.
In fungi, meiotic drive is observed as spore killing. In the secondarily homothallic ascomycete Podospora anserina it is characterized by the abortion of two of the four spores in the ascus. We have identified seven different types of meiotic drive elements (Spore killers). Among 99 isolates from nature, six of these meiotic drive elements occurred in a local population. Spore killers comprise 23% of the natural population of P. anserina in Wageningen, The Netherlands, sampled from 1991 to 1997. One Spore-killer type was also found in a French strain dating from 1937. All other isolates found so far are sensitive to spore killing. All seven Spore killer types differ in the percentage of asci that show killing and in their mutual interactions. Interactions among Spore killer types showed either mutual resistance or dominant epistasis. Most killer elements could be assigned to linkage group III but are not tightly linked to the centromere.
Chromosomally-induced meiotic drive in Drosophila males: Checkpoint or fallout?
4347Tomkiel, JE, Genetica, 109:95-103. 2000-01-05 00:00:00.
In male Drosophila melanogaster, anomalies in sex chromosome pairing at meiosis often lead to complete or partial sperm dysfunction. This observation has led to the suggestion that defects in either the efficiency or configuration of chromosome pairing at metaphase trigger a checkpoint mechanism that leads to the elimination of meiotic products. Here, we discuss this model in consideration of recent observations on the conservation of metaphase checkpoint components in male meiosis, and on the phenotype of new alleles of the male-specific meiotic mutant teflon. Based on these observations, we propose an alternative hypothesis for the cause of sperm dysfunction in cases of chromosomal sterility and drive. We suggest that disruption of the prophase compartmentalization of sex chromatin, rather than abnormal pairing at metaphase, may be the causative defect. Such disruption may occur as a result of perturbations in sex chromosome pairing, or by translocations involving autosomal and sex chromatin. We discuss how this hypothesis may account for previously described examples chromosomal causes of meiotic drive and sterility in Drosophila.
Segregation distortion of mouse t-haplotypes: The molecular basis emerges
4346Schimenti, J, Trends in Genetics, 16:240-243. 2000-01-04 00:00:00.
The t haplotype is an ancestral version of proximal mouse chromosome 17 that has evolved mechanisms to persist as an intact genomic variant in mouse populations. t haplotypes contain mutations that affect embryonic development, male fertility and male transmission ratio distortion (TRD), Collectively, these mutations drive the evolutionary success of t haplotypes, a phenomenon that remains one of the longstanding mysteries of mouse genetics. Molecular genetic analysis of TRD has been confounded by inversions that arose to lock together the various elements of this complex trait. Our first molecular glimpse of the TRD mechanism has finally been revealed with the cloning of the t complex responder (Tcr) locus, a chimeric kinase with a genetically cis active effect. Whereas + sperm in a +/t male have impaired flagellar function caused by the deleterious action of trans-active, t-haplotype-encoded 'distorters,' the mutant activity of Tcr counterbalances the distorter effects, maintaining the motility and fertilizing ability of t sperm.
Physical mapping of male fertility and meiotic drive quantitative trait loci in the mouse t complex using chromosome deficiencies
4345Planchart, AY, Y.; Schimenti, J. C., Genetics, 155:803-812. 2000-01-03 00:00:00.
The t complex spans 20 cM of the proximal region of mouse chromosome 17. A variant form, the t haplotype (t), exists at significant frequencies in wild mouse populations and is characterized by the presence of inversions that suppress recombination with Mild-type (+) chromosomes. Transmission ratio distortion and sterility are associated with t and affect males only. It is hypothesized that these phenomena are caused by trans-acting distorter/sterility factors that interact with a responder locus (Tcr(t)) and that the distorter and sterility factors are the same because homozygosity of the distorters causes male sterility. One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion. To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region. The find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1. YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1. We present evidence for the existence of multiple proximal t complex regions that exhibit distorter activity. These studies demonstrate the utility of chromosome deletions for complex trait analysis.
Genetic and molecular characterization of sting, a gene involved in crystal formation and meiotic drive in the male germ line of Drosophila melanogaster
4362Schmidt, AP, G.; Bozzetti, M. P.; Tritto, P.; Pimpinelli, S.; Schafer, U., Genetics, 151:749-760. 1999-01-20 00:00:00.
The sting mutation, caused by a P element inserted into polytene region 32D, was isolated by a screen for male sterile insertions in Drosophila melanogaster. This sterility is correlated with the presence of crystals in spermatocytes and spermatids that are structurally indistinguishable from those produced in males carrying a deficiency of the Y-linked crystal (cry) locus. In addition, their morphology is needle-like in Ste(+) flies and star-shaped in Ste flies, once again as observed in cry(-) males. The sti mutation leads to meiotic drive of the sex chromosomes, and the strength of the phenomenon is correlated with the copy number of the repetitive Ste locus. The same correlation is also true for the penetrance of the male sterile mutation. A presumptive sti null allele results in male sterility and lethal maternal effect. The gene was cloned and shown to code for a putative protein that is 866 amino acids long. A C-terminal domain of 52 amino acids is identified that is well conserved in proteins from different organisms. The gene is expressed only in the germline of both sexes. The interaction of sting with the Ste locus can also be demonstrated at the molecular level. While an unprocessed 8-kb Ste primary transcript is expressed in wild-type males, in X/Y-homoozygous sti males, as in X/Y cry(-) males, a 0.7-kb mRNA is produced.
Meiotic drive and evolution of female choice
4361Reinhold, KE, L.; Misof, B.; Kurtz, J., Proceedings of the Royal Society B-Biological Sciences, 266:1341-1345. 1999-01-19 00:00:00.
As a special version of the good-genes hypothesis, it was recently proposed that females could benefit from choosing drive-resistant males in a meiotic drive system. Here, we examine with a three-locus, six-allele population genetic model whether female choice for drive resistance can evolve. An allele leading to female preference for drive-resistant males was introduced at low frequency into a population polymorphic for meiotic drive and drive resistance. Our simulations show that female choice of drive-resistant males is disadvantageous when resistance is Y-linked. This disadvantage occurs because, at equilibrium, drive-resistant males have lower reproductive success than drive-susceptible males. Thus, female choice of drive-susceptible males can evolve when resistance is Y-linked. When resistance is autosomal, selection on female choice for drive resistance is less strong and depends on the frequency of choice: female preference of resistant males is favoured when choice is rare and disadvantageous when choice is frequent, leading to a stable equilibrium at a low frequency of the choice allele. Independent of the location of drive resistance alleles, males with the non-driving allele always have above average reproductive success. Female choice is therefore beneficial when choosy females prefer males with the non-driving allele.
Transmission ratio distortion in females on chromosome 10p11-p15
4360Paterson, ADP, A., American Journal of Medical Genetics, 88:657-661. 1999-01-18 00:00:00.
A number of recent reports of linkage of markers on chromosome 10p to schizophrenia, and evidence for linkage in one study to bipolar affective disorder, provide encouragement for psychiatric genetics, after nonreplication of linkage findings at other chromosomal regions, The same region on chromosome 10 also demonstrates evidence for linkage to obesity, female alcoholism, and female type 1 diabetes. However, evidence for linkage can be confounded by the biological phenomenon of transmission ratio distortion. Transmission ratio distortion (also termed segregation distortion or meiotic drive) results in non-Mendelian segregation of alleles to live born offspring, and has not been investigated at the majority of loci for complex traits. We examined evidence for transmission ratio distortion using 40 Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees across chromosome 10 using CEPH genotype data. Evidence for linkage of females to D10S211 was found (multipoint non-parametric linkage Z score [NPL] = 1.84, P = 0.040), while there was no linkage of this marker to male sex, The observation of possible transmission ratio distortion in females on chromosome 10p requires additional study, and may impact on the interpretation of positive linkage findings in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:657-661, 1999. (C) 1999 Wiley-Liss, Inc.
Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila
4359Merrill, CB, L.; Kusano, A.; Ganetzky, B., Science, 283:1742-1745. 1999-01-17 00:00:00.
Segregation Distorter (SD) in Drosophila melanogaster is a naturally occurring meiotic drive system in which the SD chromosome is transmitted from SD/SD+ males in vast: excess over its homolog owing to the induced dysfunction of SD+-bearing spermatids. The Sd Locus is the key distorting gene responsible for this phenotype. A genomic fragment from the Sd region conferred full distorting activity when introduced into the appropriate genetic background by germline transformation. The only functional product encoded by this fragment is a truncated version of the RanGAP nuclear transport protein. These results demonstrate that this mutant RanGAP is the functional Sd product.
How common are meiotically driving sex chromosomes in insects?
4357Jiggins, FMH, G. D. D.; Majerus, M. E. N., American Naturalist, 154:481-483. 1999-01-15 00:00:00.
In summary, we argue that the hypothesis that sex chromosome; meiotic drive is common within the insects is in; fact not proved. We feel that, although it is unlikely that; it will be found exclusively in the Diptera, there is a case; to be made that the Diptera are a hot spot for the occurrence; of sex chromosome meiotic drive. Further research; is clearly necessary to clarify this point. If the Diptera; are found to be different, then we must ask why this; is so. Meiotic drive often involves the destruction of gametes; that do not bear the drive allele causing a reduction; in the number of functional gametes. This may mean that; meiotically driving sex chromosomes are unlikely to spread; in female heterogametic taxa such as the Lepidoptera because; a reduction in the number of eggs is more costly; than a reduction in the number of sperm. Among male; heterogametic taxa, it is unclear what could make Dipteran; meiosis special.
Segregation distortion in a deme structured population: opposing demands of gene, individual and group selection
4364van Boven, MW, F. J., Journal of Evolutionary Biology, 12:80-93. 1999-01-02 00:00:00.
The evolution of segregation distortion is governed by the interplay of selection at different levels. Despite their systematic advantage at the gamete level, none of the well-known segregation distorters spreads to fixation since they induce severe negative fitness effects at the individual level. In a deme-structured population, selection at the population level also plays a role. By means of a population genetical model, we analyse the various factors that determine the success of a segregation distorter in a metapopulation, Our focus is on the question of how the success of a distorter allele is affected by its segregation ratio and its fitness effects at the individual level. The analysis reveals that distorter alleles with high segregation ratios are the best invaders and reach the highest frequencies within single demes. However, the productivity of a deme harbouring a distorter with a high segregation ratio may be significantly reduced. As a consequence, an efficient distorter will be underrepresented in the migrant pool and, moreover, it may increase the probability of deme extinction. In other words, efficient distorters with high segregation ratios may well succumb to their own success. Therefore, distorters with intermediate segregation ratios may reach the highest frequency in the metapopulation as a result of the opposing forces of gamete, individual and group selection. We discuss the implications of this conclusion for the t complex of the house mouse.
Meiotic drive favors Robertsonian metacentric chromosomes in the common shrew (Sorex araneus, Insectivora, Mammalia)
4380Wyttenbach, AB, P.; Hausser, J., Cytogenetics and Cell Genetics, 83:199-206. 1998-01-18 00:00:00.
Meiotic drive has attracted much interest because it concerns the robustness of Mendelian segregation and its genetic and evolutionary stability. We studied chromosomal meiotic drive in the common shrew (Sorex araneus, Insectivora, Mammalia), which exhibits one of the most remarkable chromosomal polymorphisms within mammalian species. The open question of the evolutionary success of metacentric chromosomes (Robertsonian fusions) versus acrocentrics in the common shrew prompted us to test whether a segregation distortion in favor of metacentrics is present in female and/or male meiosis. Performing crosses under controlled laboratory conditions with animals from natural populations, we found a clear trend toward a segregation distortion in favor of metacentrics during male meiosis, two chromosome combinations (gm and ji) being significantly preferred over their acrocentric homologs. Apart for one Robertsonian fusion (hi), this trend was absent in female meiosis. We propose a model based on recombination events between twin acrocentrics to explain the difference in transmission ratios of the same metacentric in different sexes and unequal drive of particular metacentrics in the same sex. Pooled data for female and male meiosis revealed a trend toward stronger segregation distortion for larger metacentrics. This is partially in agreement with the frequency of metacentrics occurring in natural populations of a chromosome race showing a high degree of chromosomal polymorphism.
Male eye span in stalk-eyed flies indicates genetic quality by meiotic drive suppression
4379Wilkinson, GSP, D. C.; Crymes, L., Nature, 391:276-279. 1998-01-17 00:00:00.
In some species, females choose mates possessing ornaments that predict offspring survival(1-5). However, sexual selection by female preference for male genetic quality(6-8) remains controversial because conventional genetic mechanisms maintain insufficient variation in male quality to account for costly preference and ornament evolution(9,10). Here we show that females prefer ornaments that indicate genetic quality generated by transmission conflict between the sex chromosomes, By comparing sex-ratio distributions in stalk-eyed fly (Cyrtodiopsis) progeny we found that female-biased sex ratios occur in species exhibiting eye-stalk sexual dimorphism(11,12) and female preferences for long eye span(13,14). Female-biased sex ratios result from meiotic drive(15), the preferential transmission of a 'selfish' X-chromosome. Artificial selection for 22 generations on male eye-stalk length in sexually dimorphic C. dalmanni produced longer eye-stalks and male-biased progeny sex ratios in replicate lines. Because male-biased progeny sex ratios occur when a drive-resistant Y chromosome pairs with a driving X chromosome(15), long eye span is genetically linked to meiotic drive: suppression. Male eye span therefore signals genetic quality by influencing the reproductive value of offspring(16).
Evolution of segregation distortion: Potential for a high degree of polymorphism
4377van Boven, MW, F. J., Journal of Theoretical Biology, 192:131-142. 1998-01-15 00:00:00.
By means of a population genetical model, we study the evolution of segregation distortion. Most models of segregation distortion focus on a single distorter allele. In contrast, we consider the competition between a large number of distorters. Motivated by systems as the t complex of the house mouse or the Sd complex of Drosophila melanogaster, we assume that there is some "complementation" between distorter alleles, i.e. that the fitness of individuals heterozygous for two distorter alleles is higher than the fitness of homozygous individuals. In the presence of complementation, the most efficient distorter allele with the highest segregation ratio often does not outcompete less efficient distorters. In fact, our results show that coexistence of a large number of distorter alleles is more typical than the competitive exclusion of less efficient distorters by a single superior allele. We first consider the analytically tractable system where all distorters show the same amount of complementation. In this case, all distorters with a segregation ratio higher than a certain critical value will persist, resulting in a polymorphic population where the average segregation ratio is only slightly larger than 0.5. If the degree of complementation varies, there may be more than one stable equilibrium, and the outcome of competition may depend on the initial conditions. Motivated by empirical examples, we also consider the case that the distorting ability of an allele is negatively related to its effects on individual fitness. Interestingly, the outcome of competition depends crucially on details of such a trade-off. We conclude that verbal arguments are insufficient to predict the evolution of segregation distortion. (C) 1998 Academic Press Limited.
Male sterility and meiotic drive associated with sex chromosome rearrangements in Drosophila: Role of X-Y pairing
4375McKee, BDW, K.; Merrill, C.; Ren, X. J., Genetics, 149:143-155. 1998-01-13 00:00:00.
In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh(-)/Y males, and to restore fertility to Xh(-)/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.
Segregation distortion in myotonic dystrophy
4374Magee, ACH, A. E., Journal of Medical Genetics, 35:1045-1046. 1998-01-12 00:00:00.
Myotonic dystrophy (DM) is an autosomal dominant disease which, in the typical pedigree, shows a three generation anticipation cascade. This results in infertility and congenital myotonic dystrophy (CDM) with the disappearance of DM in that pedigree. The concept of segregation distortion, where there is preferential transmission of the larger allele at the DM locus, has been put forward to explain partially the maintenance of DIM in the population. In a survey of DM in Northern Ireland, 59 pedigrees were ascertained. Sibships where the status of all the members had been identified were examined to determine the transmission of the DM expansion from affected parents to their offspring. Where the transmitting parent was male, 58.3% of the offspring were affected, and in the case of a female transmitting parent, 68.7% were affected. Studies on meiotic drive in DIM have shown increased transmission of the larger allele at the DM locus in non-DIM heterozygotes for CTGn. This study provides further evidence that the DM expansion tends to be transmitted preferentially.
Sex ratio distortion in Acraea encedon (Lepidoptera : Nymphalidae) is caused by a male-killing bacterium
4373Jiggins, FMH, G. D. D.; Majerus, M. E. N., Heredity, 81:87-91. 1998-01-11 00:00:00.
Females of the butterfly Acraea encedon produce either entirely female offspring or males and females in an almost 1:1 sex ratio. The sex ratio produced is maternally inherited and was previously attributed to sex chromosome meiotic drive. We report that all-female lineages are associated with low egg-hatching rates and that the trait is cured by antibiotic treatment. We thus reject the hypothesis that this sex ratio bias is caused by a meiotically driven sex chromosome and, instead, propose that it is associated with a maternally inherited bacterium that kills males.
Selfish genes and meiotic drive
4372Hurst, LD, Nature, 391:223-223. 1998-01-10 00:00:00.
Work by Gerald Wilkinson and colleagues3 on stalk-eyed flies (Diopsidae), described on page 276, provides the strongest evidence to date about the nature of some of the genes females prefer. As their name suggests, stalk-eyed flies have their eyes perched on the end of side-projecting stalks (see the cover of this issue). These can reach ridiculous proportions. In two of the species studied, males have considerably greater eye span than females, and male eye span even exceeds body length. In both of these species females show a strong preference for males with a large eye span. In a third species, male eye span was much shorter (indeed no different to female eye span) and there was no female choice.
Non-Mendelian transmission at the Machado-Joseph disease locus in normal females: Preferential transmission of alleles with smaller CAG repeats
4389Rubinsztein, DCL, J., Journal of Medical Genetics, 34:234-236. 1997-01-07 00:00:00.
Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is a neurodegenerative disorder which is associated with a CAG repeat expansion in the MJD1 gene on chromosome 14q32.1. A recent study reported an excess of transmission of disease chromosomes relative to normal chromosomes from affected fathers, while this phenomenon was not observed in female meioses. These data were compatible with meiotic drive. We investigated the transmission of alleles with larger versus smaller CAG repeat numbers in the MJD1 gene in normal heterozygotes from the 40 CEPH families. Our data suggest that there was no segregation distortion in male meioses, while the smaller CAG allele was inherited in 57% of female meioses (p<0.016). The pattern of inheritance of smaller versus larger CAG alleles at this significantly different when female meioses were compared (p=0.0139). While previous data suggest that meiotic drive may be a feature of certain human diseases, including the trinucleotide diseases MJD, myotonic dystrophy, and dentatorubral-pallidoluysian atrophy, these data are compatible with meiotic drive also occurring among non-disease associated CAG sizes.
Sex chromosome meiotic drive in stalk-eyed flies
4388Presgraves, DCS, E.; Wilkinson, G. S., Genetics, 147:1169-1180. 1997-01-06 00:00:00.
Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (X-d). Relatively high frequencies of X-d in C. dalmanni and C. whitei (13-17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of X-d. Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with X-d, modifying Y chromosomes (Y-m) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex linked polymorphisms and consider the impact of X-d on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.
Selected lines of Aedes aegypti with persistently distorted sex ratios
4386OwusuDaaku, KOW, R. J.; Butler, R. D., Heredity, 79:388-393. 1997-01-04 00:00:00.
A breeding scheme to isolate X chromosomes sensitive to drive by the T8 (Trinidad) Y chromosome of Aedes aegypti (the MD haplotype) is reported. Crosses with an Australian strain Th.I (Thursday Island) revealed not only sensitive and resistant X chromosomes but also some with the capacity to drive against the T8 Y chromosome. Four strains were created in which sex ratio was male-distorted (28-36 per cent female) for 10 generations, with no regression towards sexual parity. The proportion of females varied significantly between generations in each of the four strains. Further selection produced strains with normal sex ratios, capable of generating fewer than 15 per cent female on outcrossing to T8 males.
Abnormal spermiogenesis is associated with the X-linked sex-ratio trait in Drosophila simulans
4385MontchampMoreau, CJ, D., Heredity, 79:24-30. 1997-01-03 00:00:00.
The sex-ratio trait, known in several Drosophila species, results from X-linked meiotic drive that affects Y-bearing sperm and causes males to produce female-biased progeny. We describe spermiogenesis in three types of D, simulans males: wild-type, sex-ratio, and males that bear driver X chromosomes but do not express the sex-ratio trait because of autosomal and Y-linked suppression, Sex-ratio males show numerous spermatid nuclei in abnormal positions throughout their cysts, which occurs rarely, if ever, in the two other types, The degree of the spermiogenic failure in sex-ratio males is correlated with the bias towards females in their progeny. This proves that: the trait is a case of meiotic drive and strongly suggests that the abnormal spermatids are Y-bearing ones, The number of cysts per testis, hence the production of X-bearing sperm. is not increased in sex-ratio males. Implications for the spread of the sex-ratio trait in natural populations of D. simulans are discussed.
Segregation distortion in unstructured and structured populations: Competition between ‘sterile’ t haplotypes
4403VanBoven, MW, F. J., Netherlands Journal of Zoology, 46:216-226. 1996-01-21 00:00:00.
By means of two simple models we investigate the competition between sex-specific segregation distorters in unstructured and structured populations. The models are motivated by the t complex of the house mouse. Some variants at this gene complex, the t haplotypes, distort Mendelian segregation in their favour in heterozygous males. The selective advantage at the gamete level is counterbalanced by strong negative fitness effects at the individual level. A large number of t haplotypes with varying degrees of segregation distortion has been found. In order to address this phenomenon we explicitly model the competition between two t haplotypes which induce male sterility when homozygous. Surprisingly, a distorter which is inferior at the gamete level and equivalent in every other respect to a more efficient distorter may well persist in a population. We argue that rare distorters are inherently favoured, and that, as a result, fitness considerations alone are not sufficient to predict the outcome of competition. Since 'sterile' t haplotypes are not only influenced by gamete and individual selection, but also by selection at the level of the group, we furthermore study the relation between unstructured and structured populations. It is shown that the persistence of a seemingly inferior distorter is also possible in a structured population. In contrast, a single efficient distorter with high segregation ratio may not even be able to persist in a structured population. Hence, in a metapopulation with migration between local demes, the segregation ratio is an even worse predictor of the evolutionary success of a segregation distorter than in an unstructured population.
Competition between segregation distorters: Coexistence of ”superior” and ”inferior” haplotypes at the t complex
4402vanBoven, MW, F. J.; Heg, D.; Huisman, J., Evolution, 50:2488-2498. 1996-01-20 00:00:00.
By means of population genetical models, we investigate the competition between sex-specific segregation distorters. Although the models are quite general, they are motivated by a specific example, the t complex of the house mouse. Some variants at this gene complex, the t haplotypes. distort Mendelian segregation in heterozygous males in their favor. The selective advantage at the gamete level is counterbalanced by strong negative fitness effects at the individual level (male sterility or even lethality in both sexes). A plethora of different t haplotypes has been found, both in the field and in the lab. Up to now, however, models have focused on the equilibrium frequency of a single t haplotype. In contrast, we explicitly model the competition between several t haplotypes, A deterministic model for a large, well-mixed population predicts a surprisingly high degree of polymorphism. Haplotypes with seemingly inferior fitness characteristics may easily coexist with ''superior'' haplotypes. For instance, a lethal haplotype with a low segregation ratio may stably coexist with a sterile haplotype with a high segregation ratio, Stable coexistence is even possible for haplotypes with a segregation disadvantage. A simple stochastic model shows that the same principles apply in the context of a structured metapopulation. Although counterintuitive at first sight, all our results can be explained by the fact that segregation distorters have an inherent advantage when they are rare. We conclude that fitness comparisons are not sufficient to predict the outcome of competition when selective forces are acting at different levels.
Meiotic drive in fungi: Chromosomal elements that cause fratricide and distort genetic ratios
4399Raju, NB, Journal of Genetics, 75:287-296. 1996-01-17 00:00:00.
Fungal Spore killers (Sk), studied most extensively in Neurospora and to a lesser extent in Podospora, Gibberella and Cochliobolus, cause the death of ascospores (= meiospores) that do not contain the killer (Sk(K)) element. When a Spore killer is heterozygous (Sk(K) x Sk(S)) in Neurospora, every ascus (= meiocyte) contains four normal-sized, black, viable ascospores (Sk(K)), and four ascospores that are tiny, unpigmented and unviable (Sk(S)). Killing of sensitive nuclei is expressed postmeiotically, and results in gross distortion of segregation ratios for Sk-linked genes. A sensitive nucleus that would otherwise die is rescued if a killer nucleus is also enclosed in the same ascospore. In Neurospora, Sk is centromere-linked (linkage group III), and when heterozygous, shows a recombination block in a 30-map-unit region spanning the centromere of linkage group III. There is no ascospore death or recombination block in killer x killer or sensitive x sensitive crosses. Spore killers are Fairly common in Gibberella fujikuroi and Neurospora sitophila but extremely rare in N. intermedia, and have not yet been found among natural isolates of N. crassa.
Epistatic control of non-mendelian inheritance in mouse interspecific crosses
4398Montagutelli, XT, R.; Nadeau, J. H., Genetics, 143:1739-1752. 1996-01-16 00:00:00.
Strong deviation of allele frequencies from Mendelian inheritance favoring Mus spretus-derived alleles has been described previously for X-linked loci in four mouse interspecific crosses. We reanalyzed data for three of these crosses focusing on the location of the gene(s) controlling deviation on the X-chromosome and the genetic basis for incomplete deviation. At least two loci control deviation on the X chromosome, one near Xist (the candidate gene controlling X inactivation) and the other more centromerically located. In all three crosses, strong epistasis was found between loci near Xist and marker loci on the central portion of chromosome 2. The mechanism for this deviation from Mendelian expectations is not yet known but it is probably based on lethality of embryos carrying particular combinations of alleles rather than true segregation distortion during oogenesis in F-1 hybrid females.
Analysis of meiotic segregation, using single-sperm typing: Meiotic drive at the myotonic dystrophy locus
4396Leeflang, EPM, M. S.; Arnheim, N., American Journal of Human Genetics, 59:896-904. 1996-01-14 00:00:00.
Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of single sperm from three individuals heterozygous at the DM locus, each with one allele larger and one allele smaller than 19 CTG repeats. To guard against the possible problem of differential PCR amplification rates based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelated to the allele size at the DM locus. Using statistical models specifically designed to study single-sperm segregation data, we find no evidence of meiotic segregation distortion. The upper limit of the two-sided 95% confidence interval for the estimate of the common segregation probability for the three donors is at or below .515 for all models considered, and no statistically significant difference from .5 is detected in any of the models. This suggests that any greater amount of segregation distortion at the myotonic dystrophy locus must result from events following sperm ejaculation. The mathematical models developed make it possible to study segregation distortion with high resolution by using sperm-typing data from any locus.
The mouse t-complex-encoded protein Tctex-1 is a light chain of brain cytoplasmic dynein
4395King, SMD, J. F.; Benashski, S. E.; Lye, R. J.; PatelKing, R. S.; Pfister, K. K., Journal of Biological Chemistry, 271:32281-32287. 1996-01-13 00:00:00.
Mammalian brain cytoplasmic dynein contains three light chains of M(r) = 8,000, 14,000, add 22,000 (King, S. M., Barbarese, E., Dillman, J. F., III, Patel-King, R. S., Carson, J. H., and Pfister, K. Kr (1996) J. Biol. Chem. 271, 19358-19366). Peptide sequence data (16/16 residues correct) implicate the M(r) = 14,000 polypeptide as Tctex-1, a protein encoded within the mouse t-complex. Tctex-1 cosediments with microtubules and is eluted with ATP or salt but not with GTP as expected for a dynein subunit, The ATP-eluted protein precisely cosediments with known cytoplasmic dynein proteins in sucrose density gradients, Tctex-1 also is immunoprecipitated from brain and other tissue homogenates by a monoclonal antibody raised against the 74-kDa cytoplasmic dynein intermediate chain, Quantitative densitometry indicates that Tctex-1 is a stoichiometric component of the dynein complex, As Tctex-1 is a candidate for involvement in the transmission ratio distortion (meiotic drive) of mouse t-haplotypes, these results suggest that cytoplasmic dynein dysfunction may play an important role in non-mendelian chromosome segregation.
Further evidence consistent with Stellate’s involvement in meiotic drive
4394Hurst, LD, Genetics, 142:641-643. 1996-01-12 00:00:00.
STELLATE is an X-linked multicopy gene found in Drosophila melanogaster and is one of the most bizarre gene arrays yet described (for details see HARDY et al. 1984; LIVAK 1984, 1990; DANILEVSKAYA et al. 1991; BAW~REVA et al. 1992; SHEVELYOV 1992; PALUMBO et al. 1994). The activity of Stellate is restricted to spermatogenesis. However, the transcription and translation of Stellate is inhibited in most males by a Y-linked multicopy gene, Suppressor of Stellate (Su(Ste)) alias crystal (q) . If Stellate is not suppressed, then the protein product (homologous to the beta subunit of casein kinase 11) is produced at levels dependent upon the copy number of Stellate. If Stellate copy number is relatively low, then linear crystals form and the males are of reduced, but nonzero, fertility. In high copy number (up to 200), however, the protein forms a star-shaped crystal in sperm, and the males are typically sterile. An understanding of this system is hence potentially of importance for the study of both intra- and inter-specific sterility and hence of HALDANE’S Rule
Evidence for B chromosome drive suppression in the grasshopper Eyprepocnemis plorans
4393Herrera, JAL, M. D.; Cabrero, J.; Shaw, M. W.; Camacho, J. P. M., Heredity, 76:633-639. 1996-01-11 00:00:00.
The grasshopper Eyprepocnemis plorans is polymorphic for both a B chromosome and a heterochromatic segment of chromatin on the smallest autosome. Females transmit these to their offspring more frequently after copulating with a male from a population without Bs than after copulating with a male from their own population. Paternity analyses using the heterochromatic segment as a marker showed that the effect of male on female transmission does not depend on fertilization because it occurs even when all the eggs are fertilized by sperm from another mating. The possible mechanisms include behavioural differences in mating and transfer of substances affecting female meiosis in male ejaculate. The data support the idea that the B chromosome is initially subject to meiotic drive in populations in which it has not previously existed, and that genes which suppress this drive are then selected.
Meiotic drive in female mice: An essay
4407Ruvinsky, A, Mammalian Genome, 6:315-320. 1995-01-05 00:00:00.
Since the rediscovery of Mendel's laws, geneticists have accumulated various examples in which equal meiotic segregation in heterozygotes is violated. However, only a few natural meiotic drive systems have been characterized in detail and the majority of these are sex chromosome linked (Hurst and Pomiankovski 1991a). In animals, only two autosomal meiotic drive systems have been thoroughly investigated: the t complex in Mus musculus (Lyon 1991; Silver 1993) and the Segregation Distorter system (SD) in Drosophila melanogaster (Lyttle 1991). Both affect heterozygous males. Recently Agulnik and associates (1990a, 1993c, 1993d) have found and described a new meiotic drive system that disturbs normal segregation in heterozygous female mice. The system is the main target of this review, which also includes a comparative analysis of other drive systems to establish a likely scenario of their origin, evolution, and stability in natural populations.
Sex-ratio distortion in Drosophila simulans – cooccurrence of a meiotic drive and a suppressor of drive
4406Mercot, HA, A.; Jacques, M.; Montchampmoreau, C., Journal of Evolutionary Biology, 8:283-300. 1995-01-04 00:00:00.
A sex-ratio distortion factor was found at high frequency in D. simulans strains from Seychelles and New Caledonia. This factor is poorly or not expressed within those strains which are resistant to it. Its presence was detected by crossing females from New Caledonia or the Seychelles with males from a different geographic origin. Most of the Fl males obtained produced an excess of females (up to 99%) in their progeny. The two strains are infected with Wolbachia, but these micro-organismms are not involved in the sex-ratio distortion. The sex-ratio factor is shown to be an X-linked meiotic driver; nuclear resistance factor(s) act by suppressing the drive. It is likely that the same X-located driver invaded the two populations, which subsequently developed resistance factor(s) against it.
Ascoycete spore killers: Chromosomal elements that distort genetic ratios among the products of meiosis
4417Raju, NB, Mycologia, 86:461-473. 1994-01-15 00:00:00.
Spore killers (Sk), studied most extensively in Neurospora, are also known in Podospora, Gibberella and Cochliobolus. Spore killers are no doubt present in natural populations of other fungi. Criteria are outlined here for recognizing their presence and distinguishing them from other causes of ascospore death. Killing occurs when one parent carries the killer element (Sk(K)) and the other carries the sensitive counterpart (Sk(S)). When heterozygous, every ascus contains four normal-sized, viable ascospores and four ascospores that are tiny, undeveloped, and inviable. Spore killers are expressed postmeiotically causing the death of ascospores that do not receive the killer element and resulting in gross distortion of allele ratios for Sk-linked genes. There is little or no ascospore death in homozygous killer x killer or sensitive x sensitive crosses. Sk(K) is centromere-linked in linkage group III of Neurospora crassa and N. intermedia. When Sk is heterozygous, crossing over is blocked in a 30 map unit region that spans the centromere. A sensitive nucleus that would otherwise die is rescued, unchanged, if a killer nucleus is also included in the same ascospore. This has been shown for a developmental giant-ascospore mutant of N, crassa and for the naturally heterokaryotic ascospores of N. tetrasperma and Podospora anserina. As with other segregation-distorters in animals and plants, fungal Spore killers have been found only among strains from nature. Spore killers are fairly common in N. sitophila and Gibberella fujikuroi, but none have been found among natural isolates of N. crassa. In N. intermedia, most strains are sensitive to killing and killers are extremely rare. Some neutral strains are found in nature. These neither kill nor are killed. Resistance to killing is conferred by loci linked to the Sk region. The significance of fungal Spore killers for the individual organism and for populations is discussed.
Characterization of 2 Segregation Distorter revertants: Evidence that the tandem duplication is necessary for SD activity in Drosophila melanogaster
4416Palopoli, MFD, P.; Wu, C. I., Genetics, 136:209-215. 1994-01-14 00:00:00.
Segregation Distorter (SD) is a naturally occurring system of meiotic drive in Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homolog (SD+) transmit predominantly SD-bearing sperm. To accomplish this, the Segregation distorter (Sd) locus induces the dysfunction of those spermatids that receive the SD+ chromosome. Recently, P. A. Powers and B. Ganetzky isolated overlapping DNA clones spanning the region of DNA known to contain the Sd gene and identified a 5-kb tandem duplication that is present on all SD chromosomes examined, but is apparently absent from wild-type chromosomes. Here we report a molecular analysis of two spontaneous revertants from an Australian SD chromosome (SD-Arm28). Both of these revertants have lost the 5-kb tandem duplication along with the ability to distort transmission; the critical observation, however, is that they retain the DNA haplotype in the flanking regions (both proximally and distally) that is characteristic of the original SD-Arm28. We propose unequal sister chromatid exchange between the tandem repeats as the only plausible explanation for loss of a repeat while retaining flanking markers. This provides direct evidence that the tandem duplication is indeed necessary for the Sd phenotype. Further, we examined testes-specific levels of both RNA and protein for the nearby Topoisomerase 2 gene. Neither revealed a consistent difference between SD and SD+ strains. We also measured testes-specific levels of RNA using the tandem duplication itself as probe. Our results suggest that there is strong up-regulation of one or several 2.0-2.3-kb transcripts from the duplicated region in the testes of an SD strain. Whether it is this overexpression of transcripts that causes segregation distortion remains to be investigated.
Functional identification of the Segregation Distorter locus of Drosophila melanogaster by germline transformation
4415McLean, JRM, C. J.; Powers, P. A.; Ganetzky, B., Genetics, 137:201-209. 1994-01-13 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in D. melanogaster that results in the failure of SD/SD+ males to transmit SD+ homologs owing to the induced dysfunction of spermatids carrying the normal chromosome. Segregation distorter (Sd), the gene primarily responsible for this distorted transmission, is associated with a novel 12-kb restriction fragment containing a tandem duplication of a 5-kb wild-type segment of genomic DNA. When introduced into appropriate genetic backgrounds by germline transformation, this 12-kb fragment causes full levels of distortion and directs the expression of an Sd-specific 4-kb transcript. Transformants that have lost part of this segment are unable to cause distortion and do not express the 4-kb transcript. These results identify the tandem duplication as Sd.
Meiotic drive at the myotonic dystrophy locus
4413Gennarelli, MD, B.; Baiget, M.; Martorell, L.; Novelli, G., Journal of Medical Genetics, 31:980-980. 1994-01-11 00:00:00.
The mutation underlying myotonic dystrophy (DM, MIM* 160900) is the expansion of a CTG trinucleotide repeat sequence at the 3' untranslated region of a protein kinase gene (MT-PK).' The kinetics of this process is influenced by the sex of the transmitting parent and size of the parental allele.2 Congenital DM (CDM) occurs almost always with maternal transmission. Only two patients with CDM have proven paternal inheritance.5' Maternal transmission is considered to be the result of a large intergenerational increase of the CTG repeat size,7 while repeat length contractions are more likely inherited if the mutated allele is of paternal origin.8 However, the range of expansions is wider for alleles transmitted by fathers with fewer than 100 repeats (range 41 to 95).9 This has suggested a male bias in the generation of new contracted or expanded DM alleles.'° Carey et all' described an unusual segregation of the MT-PK alleles with a CTG number > 19 in healthy persons heterozygous for repeats in the wild type size range, and suggested the possibility of meiotic drive at the DM locus
The Segregation Distorter (SD) complex and the accumulation of deleterious genes in laboratory strains of Drosophila melanogaster
4423Dominguez, AS, E.; Albornoz, J.; Gutierrez, A., Theoretical and Applied Genetics, 87:479-486. 1993-01-21 00:00:00.
Segregation Distorter (SD) associated with the second chromosome of D. melanogaster is found in nature at equilibrium frequencies lower than 5%. We report extremely high frequencies of SD (30-50%) in two selected strains, established in 1976, and show it to be responsible for the accumulation of deleterious genes in chromosome II. Samples of chromosomes extracted over a 4-year period were characterized with respect to distortion, sensitivity, lethality, sterility, and inversions. SD chromosomes were inversion-free as they have been shown to be in the Mediterranean area. The cosmopolitan inversion In(2L)t was found associated with SD+ chromosomes. Lines polymorphic for SD have accumulated linked lethal and female-sterile genes approaching a near balanced system. It is proposed that deleterious genes linked in coupling to SD were accumulated by the balancing effect of distortion, while drift and restricted recombination account for the accumulation of deleterious genes linked in repulsion by a mechanism similar to Muller's ratchet. Our results should not be viewed as a particular case as SD chromosomes associated with detrimental genes and inversions are present in almost all populations around the world. The system could evolve in the way we describe whenever equilibrium conditions are broken down in small populations and lead to an increase in SD frequency.
Autosomal suppressors of sex-ratio in Drosophila mediopunctata
4422Decarvalho, ABK, L. B., Heredity, 71:546-551. 1993-01-20 00:00:00.
The sex-ratio trait has been described as the production of progenies with excess of females due to X-linked meiotic drive in the parental males. This trait has a variable expression in Drosophila mediopunctata. We describe here the existence and chromosomal localization of autosomal suppressors of sex-ratio in this species. There are at least four such genes (one on each major autosome) and the strongest effect.is localized on chromosome IV. These genes possibly result from the operation of 'Fisher's Principle'; a mechanism of Natural Selection leading to a 1:1 sex ratio.
Didymium iridis reproductive systems: Additions and meiotic drive
4421Clark, JL, J. C., Mycologia, 85:764-768. 1993-01-19 00:00:00.
Three heterothallic Mexican isolates (Mex 1, Mex 2, and Mex 3) of Didymium iridis belong to the reproductively isolated A5 mating series of this morphospecies. This was unexpected in that the sole previous A5 isolate was from Georgia and the Mexican isolates were collected in southern Mexico adjacent to the Central American Al series region. The Mexican isolates were also unusual in that mating alleles did not generally segregate in a normal 1:1 ratio. The A5(3) or A5(4) mating types, when present in a plasmodium, caused the partial or total elimination of the other mating allele during growth or sporulation. Isolates from Guatemala (Gua 2) and Panama (Pan 8) were found to belong to the Central American Al mating series. Each of these isolates was collected as a haploid selfed plasmodium which contained a single mating type respectively designated A1(13) and A1(14). Four nonheterothallic isolates from California (Ca 8), Guatemala (Gua 1), Japan (jap 1) and South Africa (SA 2) were also investigated.
The peculiar journey of a selfish chromosome: Mouse t-haplotypes and meiotic drive
4428Silver, LM, Trends in Genetics, 9:250-254. 1993-01-06 00:00:00.
Mouse t haplotypes are descendents of a variant form of chromosome 17 that evolved the ability to propagate itself at the expense of the wild-type homolog from heterozygous +/t males. Although once enigmatic, these widespread selfish chromosomes have revealed many of their secrets in response to a combined assault with molecular, genetic and phylogenetic techniques. This review summarizes the current understanding of t haplotypes and their raison d'etre.
Evolutionary dynamics of spore killers
4426Nauta, MJH, R. F., Genetics, 135:923-930. 1993-01-04 00:00:00.
Spore killing in ascomycetes is a special form of segregation distortion. When a strain with the Killer genotype is crossed to a Sensitive type, spore killing is expressed by asci with only half the number of ascospores as usual, all surviving ascospores being of the Killer type. Using population genetic modeling, this paper explores conditions for invasion of Spore killers and for polymorphism of Killers, Sensitives and Resistants (which neither kill, nor get killed), as found in natural populations. The models show that a population with only Killers and Sensitives can never be stable. The invasion of Killers and stable polymorphism only occur if Killers have some additional advantage during the process of spore killing. This may be due to the effects of local sib competition or some kind of ''heterozygous'' advantage in the stage of ascospore formation or in the short diploid stage of the life cycle. This form of segregation distortion appears to be essentially different from other, well-investigated forms, and more field data are needed for a better understanding of spore killing.
Cheaters sometimes prosper: Distortion of Mendelian segregation by meiotic drive
4425Lyttle, TW, Trends in Genetics, 9:205-210. 1993-01-03 00:00:00.
Two of Mendel's three laws were quickly discarded as information on the organization and transmission of genes accumulated at the beginning of this century, but bis law of segregation has shown remarkable staying power. In fact, within most of population genetic theory for sexual diploids is buried the tacit assumption that heterozygous alleles are represented in gametes in a 1:1 ratio. Nevertheless, there is a small, but important, group of genetic systems that subvert the law of segregation, and show 'meiotic drive.'
Divergence of meiotic drive-suppression systems as an explanation for sex-biased hybrid sterility and inviability
4442Frank, SA, Evolution, 45:262-267. 1991-01-20 00:00:00.
Two empirical generalizations about speciation remain unexplained: the tendency of the heterogametic sex to be sterile or inviable in F1 hybrids (Haldane's rule), and the tendency of the X chromosome to harbor the genetic elements that cause this sex bias in hybrid fitness. I suggest that divergence of meiotic drive systems on the sex chromosomes can explain these observations. The theory follows from two simple facts. First, sex chromosomes are particularly susceptible to the forces of meiotic drive. Second, divergence of meiotic drive systems can cause hybrid sterility and inviability. The main objection to the theory is that meiotic drive is apparently rare, whereas the observed pattern of hybrid fitness is widespread. I answer this objection by showing that divergence of meiotic drive systems can explain the two generalizations even if large departures from Mendelian segregation are rarely observed.
A comparative approach to the population genetics theory of segregation distortion
4440Feldman, MWO, Sarah P., American Naturalist, 137:443-456. 1991-01-18 00:00:00.
Mathematical models of four well-known naturally occurring systems of segregation distortion are compared. These include the sex-ratio chromosome of Drosophila pseudoobscura, the Segregation Distorter (SD) complex of D. melanogaster, the t locus in Mus musculus, and the sex-ratio system in Aedes aegypti. Dynamics of these models are compared with the classical one-locus multiple-allele viability system. For the SD complex and the sex-ratio model of A. aegypti, the role of recombination is reviewed. Departures from Mendelian segregation cause fascinating irregularities in the relationship between linkage and linkage disequilibrium, as well as in predictions for the evolution of recombination itself.
Why is Mendelian segregation so exact
4438Crow, JF, Bioessays, 13:305-312. 1991-01-16 00:00:00.
The precise 1:1 segregation of Mendelian heredity is ordinarily taken for granted, yet there are numerous examples of 'cheating' genes that perpetuate themselves in the population by biasing the Mendelian process in their favor. One example is the Segregation Distortion system of Drosophila melanogaster, in which the distorting gene causes its homologous chromosome to produce a nonfunctional sperm. This system depends on three closely linked components, whose molecular basis is beginning to be understood. The system is characterized by numerous modifiers changing the degree of distortion. Mathematical theory shows that unlinked modifiers that change the degree of distortion in the direction of Mendelism always increase in the population. This provides a mechanism for removing cheaters and preserving the honesty of the Mendelian gene-shuffle.
Segregation distortion in Drosophila melanogaster: Genetic and molecular analysis
4455Temin, RGG, B.; Powers, P. A.; Lyttle, T. W.; Pimpinelli, S.; Dimitri, P.; Wu, C. I.; Hiraizumi, Y., American Naturalist, 137:287-331. 1991-01-13 00:00:00.
The Segregation Distorter (SD) complex in the centromeric region of chromosome 2 in Drosophila melanogaster is responsible for a naturally occurring and strong system of male meiotic drive. Earlier recombinational dissection and deletional analysis showed that the SD complex resolves into three major loci: the euchromatic Sd, or Segregation distorter gene at the base of the left arm of the chromosome (2L), and two heterochromatic genes: E(SD), the Enhancer of SD, and Rsp, the Responder, in the center of the left arm and the right arm (2R), respectively. Rsp exists in the major allelic forms, Rsp(s), for sensitive, and Rsp(i), for insensitive. Males that are heterozygous for an SD chromosome (SdE(SD)Rsp(i)) and a sensitive SD+ homologue (Sd+ E(SD)+ Rsp(s)) transmit predominantly or even exclusively the SD-bearing chromosome to the progeny. The distortion of the segregation ratio is traceable to failure in chromatin condensation and maturation of those spermatids that receive the Rsp(s) homologue during meiosis. Characterization of the properties of null alleles of Sd, E(SD), and Rsp that were generated by delection determined the precise cytological locations of the components and established the functional relationship of each to its wild-type counterpart, suggesting a model whereby a deleterious action of Sd, along with E(SD), on the Rsp(s) target sets in motion the events culminating in sperm dysfunction. Further genetic analysis of E(SD), a gene required for full expression of drive, showed that E(SD) in two doses can cause significant distortion even in the absence of Sd. This distortion is suppressible by a suppressor of SD action. Thus, E(SD) is more than a simple modifier of Sd; rather, it is an effector locus that, like Sd, can act at the Rsp(s) target. Cloning and molecular analysis of the Sd locus reveal that the alteration uniquely associated with Sd is a 5-kb tandem duplication within the polytene band 37D5, which is where Sd is known to map. The Sd-associated duplication appears to be part of a large gene about 100 kb in size. A 4.2-kb SD-specific transcript has been identified, and analyses of the cDNAs indicate a complex transcription pattern. Since Responder plays such a key role in segregation distortion, recent progress in analyzing this locus has been exciting. Studies of Rsp at the genetic, cytogenetic, and molecular levels have been mutually reinforcing and consistent in demonstrating that Rsp is an extended locus that is (1) subdivisible and (2) associated with a 120-bp repeated sequence of DNA that is rich in adenine-thymine pairs and whose copy number is correlated with the degree of sensitivity. In an exceptional situation, there are certain Sd Rsp(i)/Sd+ Rsp(s) males carrying particular modifiers in which the Rsp(i) chromosome can be transmitted at frequencies of less than 0.50 relative to the Rsp(s) chromosome, suggesting that the genetics of segregation ratios may involve even further complexities, which need to be unraveled.
Expression of meiotic drive elements Spore Killer-2 and Spore Killer-3 in asci of Neurospora tetrasperma
4454Raju, NBP, D. D., Genetics, 129:25-37. 1991-01-12 00:00:00.
It was shown previously that when a chromosomal Spore killer factor is heterozygous in Neurospora species with eight-spored asci, the four sensitive ascospores in each ascus die and the four survivors are all killers. Sk-2K and Sk-3K are nonrecombining haplotypes that segregate with the centromere of linkage group III. No killing occurs when either one of these killers is homozygous, but each is sensitive to killing by the other in crosses of Sk-2K x Sk-3K. In the present study, Sk-2K and Sk-3K were transferred by recurrent backcrosses from the eight-spored species Neurospora crassa into Neurospora tetrasperma, a pseudohomothallic species which normally makes asci with four large spores, each heterokaryotic for mating type and for any other centromere-linked genes that are heterozygous in the cross. The action of Sk-2K and Sk-3K in N. tetrasperma is that predicted from their behavior in eight-spored species. A sensitive nucleus is protected from killing if it is enclosed in the same ascospore with a killer nucleus. Crosses of Sk-2K x Sk-2S, Sk-3K x Sk-3S, and Sk-2K X Sk-3K all produce four-spored asci that are wild type in appearance, with the ascospores heterokaryotic and viable. The Eight-spore gene E, which shows variable penetrance, was used to obtain N. tetrasperma asci in which two to eight spores are small and homokaryotic. When killer and sensitive alleles are segregating in the presence of E, only those ascospores that contain a killer allele survive. Half of the small ascospores are killed. In crosses of Sk-2K x Sk-3K (with E heterozygous), effectively all small ascospores are killed. The ability of N. tetrasperma to carry killer elements in cryptic condition suggests a possible role for Spore killers in the origin of pseudohomothallism, with adoption of the four-spored mode restoring ascospore viability of crosses in which killing would otherwise occur.
Meiotic drive of t haplotypes: chromosome segregation in mice with tertiary trisomy
4434Agulnik, AIA, Sergei I.; Ruvinsky, Anatoly O., Genetics Research, 57:51. 1991-01-12 00:00:00.
The properties of the / haplotypes, specific mutant states of the proximal region of chromosomes17 in the house mouse, are of continuing interest. One such property is increased transmission ofthe / haplotype by heterozygous // + males to offspring. Using the reciprocal translocationT(16; 17)43H we have constructed males with tertiary trisomy of chromosome 17( + T43/+ +/Rb7 + ) carrying the Robertsonian translocation Rb(16.17)7Bnr. Only the progeny ofthese males which had inherited either T43/ + or Rb7 from their male parent were viable. Thesegregation patterns in the offspring of /-bearing trisomics were analysed on days 16-18 ofembryonic development. It was found that, when the tn haplotype is in the normal acrocentric(c?c?+ + T43/ + //2+/Rb7 + +), its presence in the gamete +/" + /+ + T43 does not producemeiotic drive. However, when t6 is in Rb7, meiotic drive was observed: 80 % of offspring carriedthe / haplotype. It is concluded that the meiotic drive is probably inhibited by the presence of anormal homologue of chromosome 17 in the same sperm. Possible mechanisms for the t haplotypeeffect are discussed
On the components of Segregation Distortion in Drosophila melanogaster 5: Molecular analysis of the SD locus
4453Powers, PAG, B., Genetics, 129:133-144. 1991-01-11 00:00:00.
Segregation Distorter (SD) is a naturally occurring meiotic drive system comprising at least three distinct loci: Sd, Rsp and E(SD). Heterozygous SD/SD+ males transmit the SD chromosome in vast excess over the normal homolog. The distorted transmission involves the induced dysfunction of the spermatids that receive the SD+ chromosome. In the 220-kb region of DNA that contains the Sd gene, we identified a 5-kb tandem duplication that is uniquely associated with all SD chromosomes, absent in SD+ chromosomes, and detectably altered in Sd revertants. On northern blots, genomic probes from the tandem duplication detect an SD-specific 4-kb transcript in addition to several smaller transcripts present in both SD and SD+. Seven classes of cDNAs derived from these transcripts have been isolated. All of these cDNAs share extensive sequence identity at their 3' ends but differ at their 5' ends. Sequence analysis indicates that these cDNAs potentially encode four distinct, but related, polypeptides. Introduction of the tandem duplication into SD+ flies by germline transformation did not confer the dominant gain-of-function Sd phenotype. This result, taken together with our analysis of the Sd cDNAs, suggests that the duplication is part of a much larger gene that encodes several different polypeptides.
X-Y pairing, meiotic drive and ribosomal DNA in Drosophila melanogaster males
4452McKee, BD, American Naturalist, 137:332-339. 1991-01-10 00:00:00.
One of the genotypic features responsible for sex-chromosome meiotic drive and sterility in Drosophila melanogaster males has now been defined clearly. Separation of a significant fraction of X euchromatin from the X pairing site causes either meiotic drive or sterility, depending on whether the separation occurs alone or in combination with rearrangements involving the Y chromosome. The relationship between X-chromosome integrity and the late-spermatid developmental breakdowns responsible for meiotic drive and sterility is still not understood. X-Y pairing is important for some aspect of spermatogenesis in addition to its role in X-Y disjunction. Transcriptional inactivation and meiotic timing are two possibilities that are worth exploring, and there are likely to be others. With molecular probes for genes active in spermatogenesis becoming available, ideas such as the pairing dependence of transcriptional inactivation should become amenable to direct tests. It is hoped that an increased use of molecular methods will shed new light on this fascinating genetic problem.
Segregation distorters
4451Lyttle, TW, Annual Review of Genetics, 25:511-557. 1991-01-09 00:00:00.
Segregation distorters are genetic elements that exhibit the phenomenon of meiotic drive; that is, the mechanics of the meiotic divisions cause one member of a pair of heterozygous alleles or heteromorphic chromosomes to be transmitted to progeny in excess of the expected Mendelian proportion of 50% ( 1 34 , 1 36). In this review, we refer to these as genic or chromosomal drive, respectively. Genic meiotic drive is initially limited in its impact to the population dynamics of the drive locus itself and those loci fortuitiously in close linkage. Alleles at these latter loci may enjoy indirect drive through genetic hitchhiking, leading eventually to the establishment of drive haplotypes (64). The haplotype may be extended by incorporating chromosome rearrangements that reduce recombination and promote further linkage disequilibrium between the drive locus and more distant modifier loci ( 1 04 , 1 28, 1 64). In the extreme , the haplotype becomes coextensive with the chromosome, leading to a form of chromosomal meiotic drive. For a parent heterozygous for either type of drive system, the statistic k is used to denote the proportion of progeny (and by inference, successful gametes) that carry the allele or chromosome exhibiting segregation distortion. Thus , k can vary from 0 . 5 (Mendelian segregation segregation) to 1 .0 (complete segregation distortion with only one gamete class recovered in the progeny) .
Sander,Larry – The father of meiotic drive
4447Lindsley, DL, American Naturalist, 137:283-286. 1991-01-05 00:00:00.
The symposium at which the following papers were presented was deprived of what surely would have been a major intellectual contribution by the sudden death of its co-organizer, Larry Sandler, in February 1987. Larry was a leading contributor to the study of segregation distortion and meiotic drive, beginning with his seminal research as a graduate student with Ed Novitski at the University of Missouri and continuing, in collaboration with Yuichiro Hiraizumi, as a post- doctoral fellow with Jim Crow and as a fledgling faculty member at the University of Wisconsin. Many of us at the conference worked with him personally and benefited from his insights and his enthusiasm for genetic analysis of meiotic problems. We all felt a great sense of loss and missed his lively contributions at the symposium.
Molecular and chromosomal studies on the origin of t-haplotypes in mice
4444Hammer, MF, American Naturalist, 137:359-365. 1991-01-02 00:00:00.
Mouse t haplotypes are variant forms of the proximal third of chromosome 17 that enhance their representation in the gene pool by means of a male-specific transmission-ratio distortion. As with other systems of meiotic drive, they are maintained as independent genetic entities by inversions that suppress recombination with their wild-type homologues. This article reviews some of the evidence for the origin of this complex system based on DNA and chromosomal comparisons. Such comparisons suggest a stepwise evolution of t haplotypes, whereby the proximal and distal inversion occurred on separate chromosomal lineages and at different times. The initial event leading to the spread of t haplotypes may have been an inversion occurring on the wild-type chromosome (nondriving) 2-4 million yr ago. An additional implication of the data is that meiotic drive gives t haplotypes the ability to traverse species boundaries and spread rapidly around the world.
Genetics-driving genes and chromosomes
4463Charlesworth, B, Nature, 332:394-395. 1988-01-21 00:00:00.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew attention to the fact that it operates as an evolutionary force which can cause an increase in the population frequency of the allele or chromosome which is favoured in transmission, even if it confers a disadvantage on its carriers in terms of fitness at the level of the individual
Methods for replacement of malaria vector populations
4464Curtis, CFG, P. M., American Journal of Tropical Medicine and Hygiene, 91:43-48. 1988-01-02 00:00:00.
The prospects are reviewed of replacement of malaria vector populations by harmless mosquito populations by means of: (i) ecologically competitive non-vector species; (ii) natural selection due to the harmfulness of being infected; (iii) selection for insecticide resistance genes; (iv) meiotic drive; (v) negative heterosis; and (vi) hybrid dysgenesis. Serious difficulties exist with all of these approaches. At present 'dilution', i.e. release of insects carrying the desired genes without any system for forcing population replacement is the only available method. It avoids the disadvantage that, in constructing elaborate genetic 'packages', factors for low fitness may be irreversibly incorporated into them. It is debatable whether release of males only or both sexes should be attempted.
Thte genetic basis of resistance and sensitivity to the meiotic drive gene D in the mosquito Aedes aegypti L.
4469Wood, RJO, N. A., Genetica, 72:69-79. 1987-01-07 00:00:00.
A study has been made on the genetic basis of meiotic drive at the Distorter (D) locus which, in coupling with the male-determining gene (or region) M on the Y chromosome, causes production of excess male progeny. Its effect is regulated by the sensitivity/resistance of the X chromosome. This study demonstrates that there are two major loci controlling resistance/sensitivity to MD: (1) the m gene (or region) on the X chromosome (allelic with M) which may be either m R or m S (resistant or sensitive), (2) the t (tolerance) gene (or genes) which recombines with m and, if present, largely counteracts the effect of m S . There is also evidence that MD itself is capable of limited adaptation.; ; The conclusions were derived from using MD males of the T30 or ACCRA strains (from Trinidad and Ghana respectively). The work involved the use of the CHIPEI and RED strains with sensitive X chromosomes, the latter also carrying the t (tolerance) gene which is linked to re (red eye) and m (the sex-determining locus or region) but recombines with both. The implications of these findings for using MD as a method of population control are discussed.
Abnormal salivary gland puff associated with meiotic drive in mosquitos (Diptera, Culicidae)
4468Sweeny, TLG, P.; Barr, A. R., Journal of Medical Entomology, 24:623-627. 1987-01-06 00:00:00.
A meiotic drive factor, distorter (d), has been described previously for Culex pipiens L. mosquitoes. Males homozygous for the gene (Md/md) produce few female offspring owing to breakage of the female-determining dyad of chromosome 1 (the sex chromosome) during the first meiotic division of spermatogenesis. Orcein squash preparations of polytene salivary gland chromosomes of the distorter strain revealed a chromosome break and other abnormalities at zone 10C3, the location of a large puff that has been reported to be associated with sex determination in C. pipiens. In the polytene chromosomes, d apparently disrupts normal expansion and contraction of the puff. Zone 10C3 probably is also the breakpoint of the female-determining dyad. Zone 10C3 on the male-determining dyad seems to be resistant to the action of d, whereas zone 10C3 on the female-determining dyad is vulnerable to the destructive action of d. Possibly the break in the female-determining dyad occurs directly at m, the gene locus for "femaleness" in C. pipiens, in which case d may be a mutated form of m.
X-4 Translocation and meiotic drive in Drosophila melanogaster males: Role of sex chromosome pairing
4466McKee, B, Genetics, 116:409-413. 1987-01-04 00:00:00.
Males carrying certain X-4 translocations exhibit strongly skewed sperm recovery ratios. The Xp4D half of the translocation disjoins regularly from the Y chromosome and the 4‘XD half disjoins regularly from the normal 4. Yet the smaller member of each bivalent is recovered in excess of its pairing partner, apparently due to differential gametic lethality. Chromosome recovery probabilities are multiplicative; the viability of each genotype is the product of the recovery probability of its component chromosomes. Meiotic drive can also be caused by deficiency for X heterochromatin. In( I)scQLscBR males show the same size dependent chromosome recoveries and multiplicative recovery probabilities found in T(1;4)Bs males. Meiotic drive in Zn(I)scQLscBR males has been shown to be due to X-Y pairing failure. Although pairing is regular in the T(X;4) males, the striking phenotypic parallels suggest a common explanation. The experiments described below show that the two phenomena are, in fact, one and the same. X-4 translocations are shown to have the same effect on recovery of independently assorting chromosomes as does Zn(I)scqLscgR. Addition of pairing sites to the 4pXD half of the translocation eliminates drive. A common explanation-failure of the distal euchromatic portion of the X chromosome to participate in XY meiotic pairing-is suggested as the cause for drive. The effect of X chromosome breakpoint on X-4 translocation induced meiotic drive is investigated. It is found that translocations with breakpoints distal to 13C on the salivary map do not cause drive while translocations broken proximal to 13C cause drive. The level of drive is related to the position of the breakpoint-the more proximal the breakpoint the greater the drive.
Meiotic drive in the sex-chromosome system of the varying lemming, Dicrostonyx torquatus Pall (Rodentia, Microtinae)
4465Gileva, EA, Heredity, 59:383-389. 1987-01-03 00:00:00.
In the varying lemming, numerous fertile XY females occur regularly due to the X-linked mutation (X*). Their frequency both in natural populations and laboratory colonies turned out to be about twice higher than that expected under random segregation of heterochromosomes in both sexes. It has been shown in experiments that an excess of XY females resulted from a preferential segregation of the Y chromosome in males. Segregation distortion is not produced by selective embryonal mortality. Meiotic drive of the Y chromosome also causes a significant decrease of sex ratio. Although in the varying lemming meiotic drive is rather weak (the segregation ratio of the Y being 0·54–0·59), it seems to contribute essentially to the evolutionary spread and the maintenance of the X* mutation in populations. The example of Dicrostonyx and probably of other microtines also demonstrates the possible role of meiotic drive in the regulation of the population sex ratio in mammals.
Detection of Rsp and modifier variation in the meiotic drive system Segregation Distorter (SD) of Drosophila melanogaster
4470Lyttle, TWB, J. G.; Ganetzky, B., Genetics, 114:183-202. 1986-01-08 00:00:00.
Identification of allelic variability at the two major loci (Sd and Rsp) that interact to cause sperm dysfunction in Segregation distorter (SD) males of D. melanogaster has been hampered by the difficulty in separating the elements recombinationally. In addition, small differences in the strength of Sd alleles or sensitivities of Rsp alleles to Sd are difficult to measure against background genetic or environmental variation. Viability effects of the markers used to score progeny classes may also introduce a bias. Removal of Sd and E(SD) from their second chromosome location to create a Dp(2;Y)Sd E(SD) chromosome eliminates these problems, since any combination of Rsp alleles can be easily tested without resorting to recombinational techniques. Further, since these pairs of Rsp alleles are compared in their response to Dp Sd E(SD) in the same individual males, background variation and viability effects can be easily removed to allow finescale resolution of Rsp differences. Tests of all possible pairwise combination of six laboratory chromosomes in this way revealed at least three and possibly four different Rsp allelic classes. In addition, the hierarchical nature of the tests further allowed for determination of the presence of linked suppressors or enhancers of Sd activity. A sample of 11 second chromosomes selected from a group recently isolated from a natural population was also unambiguously ordered as to Rsp allelic status using this approach. The resultant pattern was similar to that obtained for the laboratory chromosomes, except for the not unexpected observation that the natural population apparently harbored more drive suppressors. The pattern of results obtained from these pairwise combinations of Rsp alleles supports the notion that there are no dominance interactions within the group, but that each responds more or less independently to Sd in giving sperm dysfunction.
Tthe genetic control of meiotic drive acting on the B-chromosome of Myrmeleotettix maculatus (Orthoptera, Aacrididae)
4473Shaw, MWH, G. M., Heredity, 54:187-194. 1985-01-11 00:00:00.
Crosses between populations with and without B-chromosomes were made, and backcrossed to the non B parent for two generations. No polygenic differences in male or female meiotic transmission were found, but a modifier of meiotic drive segregated in the experiment, drastically reducing female transmission rate. We tentatively interpret this as evidence of a coevolutionary race between the B-chromosome and the A genome.
Polymorphism in the rates of meiotic drive acting on the B-chromosome of Myrmeleotettix maculatus
4472Shaw, MWH, G. M.; Anderson, D. A., Heredity, 55:61-68. 1985-01-10 00:00:00.
A survey of all the available data on meiotic transmission rates in M. maculatus suggests that a polymorphism in female transmission rate exists in most natural populations. Differences in the frequency of the types or in the transmission rates they manifest may exist between populations or over time, but the evidence is not compelling. The data on males are also equivocal, especially because the environment may affect male transmission rate. We suggest that the polymorphism in female rates may demonstrate the selective equilibrium between the B and the genome in which it exists.
Sex-chromosome meiotic drive in Drosophila melanogaster males
4474McKee, B, Genetics, 106:403-422. 1984-01-12 00:00:00.
In Drosophila melanogaster males, deficiency for X heterochromatin causes high X-Y nondisjunction and skewed sex chromosome segregation ratios (meiotic drive). Y and XY classes are recovered poorly because of sperm dysfunction. In this study it was found that X heterochromatic deficiencies disrupt recovery not only of the Y chromosome but also of the X and autosomes, that; both heterochromatic and euchromatic regions of chromosomes are affected and that the "sensitivity" of a chromosome to meiotic drive is a function of its length. Two models to explain these results are considered. One is a competitive model that proposes that all chromosomes must compete for a scarce chromosome-binding material in Xh- males. The failure to observe competitive interactions among chromosome recovery probabilities rules out this model. The second is a pairing model which holds that normal spermiogenesis requires X-Y pairing at special heterochromatic pairing sites. Unsaturated pairing sites become gametic lethals. This model fails to account for autosomal sensitivity to meiotic drive. It is also contradicted by evidence that saturation of Y-pairing sites fails to suppress meiotic drive in Xh- males and that extra X-pairing sites in an otherwise normal male do not induce drive. It is argued that meiotic drive results from separation of X euchromatin from X heterochromatin.
The fate of autosomeal modifiers of the sex-ratio trait in Drosophila and other sex-linked meiotic drive systems.
4475Wu, CI, Theoretical Population Biology, 24:107-120. 1983-01-13 00:00:00.
A model is proposed to analyze the behavior of autosomal suppressor modifiers of "Sex-Ratio" meiotic drive in drosophila. These modifiers, if neutral in fitness, are expected to increase because they tend to be associated with the rare sex (males). However, selection operating on the sex-linked drive locus will sometimes act against autosomal modifiers as well because the two loci are always in gametic phase disequilibrium. Conditions under which modifiers will not increase are presented in terms of the relative fitness of the sex-linked drive locus. To prevent the increase of modifiers, the fitness of Sex-Ratio males relative to Standard males has to be no greater than 0.3 and there has to be overdominance in females. This model integrates findings from the search for modifiers and results from the measurement of fitness.
A theoretical-analysis of the effects of sex-chromosome aneuploidy on X-chromosome and Y-chromosome meiotic drive
4476Lyttle, TW, Evolution, 36:822-831. 1982-01-14 00:00:00.
Extra sex chromosomes are normally detrimental to the individual carrying them. In XY (or WZ) sex determining systems, an extra X chromosome in the homogametic sex generates enough X-autosome imbalance to usually cause inviability, or at least sterility. On the oth- er hand, extra Y chromosomes are some- times tolerated, although in mammals and other higher organisms where the Y is ac- tively involved in sexual development, XXY individuals are generally sterile. In Drosophila and perhaps other inverte- brates where the Y is largely genetically inert, a single extra Y may be permitted in both sexes, while two extra copies is only fertile in XXYY females (Cooper, 1956), if at all.
Meiotic drive at the D(MD) locus and fertility in the mosquito, Aedes aegypti (L)
4479Youngson, JW, H. M.; Wood, R. J., Genetica, 54:335-340. 1981-01-17 00:00:00.
The Distorter gene D in Aedes aegypti shows meiotic drive when associated with the male determining M gene, causing sex ratio distortion in favour of males. The fertility of Distorter (MD /ms) and normal (M/m-) males has been compared after mating them to a series of 20 females at daily intervals. ; Males of each genotype inseminated up to 13 fe. males (mean 8.0 - 9.0). The major difference was in the significantly greater number of inviable eggs produced by females mated to Distorter males. It is postulated that these eggs were fertilised by abnormal spermatozoa. Females mated to Distorter males also produced significantly greater numbers of shrivelled i.e. unfertilised eggs, indicating a lower density of effective spermatozoa.; The difference in percentage hatch from the two matings was small, indicating that spermatozoa were produced in superabundance so that the overall fertility of Distorter males was not greatly reduced.
A 2-locus model for polymorphism for sex-linked meiotic drive modifiers with possible applications to Aedes aegypti
4478Maffi, GJ, S. D., Theoretical Population Biology, 19:19-36. 1981-01-16 00:00:00.
A two-locus model is presented which shows the possibility of maintaining a polymorphism for modifiers of sex-linked meiotic drive in the absence of fitness differences. The model is very similar to the situation actually found in some laboratory strains of the mosquito Aedes aegypti. The existence of a stable polymorphism usually requires sufficiently loose linkage between the two loci.
Experimental population-genetics of meiotic drive systems .3: Neutralization of sex-ratio distortion in Drosophila through sex-chromosome aneuploidy
4477Lyttle, TW, Genetics, 98:317-334. 1981-01-15 00:00:00.
Laboratory populations of Drosophila melanogaster were challenged by; pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the; incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes; extreme sex-ratio distrotion and can ultimately lead to population extinction.; Populations normally respond by the gradual accumulation of drive suppressors,; and this reduction in strength of distortion allows the sex ratio to move; closer to the optimal value of 1:l. One population monitored, however, was; rapidly able to neutralize the effects of sex-ratio distortion by the accumulation; of sex-chromosome aneuploids (XXY, XYY) . This apparently occurs because; XX-bearing eggs, produced in relatively high numbers (-4%) by XXY; genotypes, become the main population source of females under strong Ychromosome; drive. Computer simulation for a discrete generation model incorporating; random mating with differences in fitness and segregation permits; several predictions that can be compared to the data. First, sex-chromosome; aneuploids should rapidly attain equilibrium, while stabilizing the population; at -60% males. This sex ratio should be roughly independent of the strength; of the meiotic drive. Moreover, conditions favoring the accumulation of drive; suppressors (e.g., weak distortion, slow population extinction) are insufficient; for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong; distortion, low production of females) lead to population extinction before drive; suppressors can accumulate. Thus, the different mechanisms for neutralizing; sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome; aneuploidy are potentially co-adaptive, since under some conditions; neither will survive alone. Finally, these results suggest the possibility that; genetic variants promoting sex-chromosome nondisjunction may have a selective; advantage in natural populations faced with sex-ratio distortion.
Combining the meiotic drive gene-D and the translocation-T1 in the mosquito, Aedes aegypti (L) .1: Sex-ratio distortion and fertility
4480Pearson, AMW, R. J., Genetica, 51:203-210. 1980-01-18 00:00:00.
Sex-ratio distortion has been investigated in males carrying the Y(M)-linked meiotic-drive gene D, from three different strains (Bozo, Caracas and Trinidad), paired with Chipei X-chromosomes highly sensitive to D. The effect of D was tested on its own and also associated with a 1-3 translocation (designated TI). The fertility of males homozygous and heterozygous for the translocation, with and without D, was also investigated
Experimental population-genetics of meiotic drive systems .2: Accumulation of genetic modifiers of Segregation Distorter (SD) in laboratory populations
4482Lyttle, TW, Genetics, 91:339-357. 1979-01-20 00:00:00.
The accumulation of modifiers of the meiotic-drive locus Segregation; Distorter (SD) in Drosophila melanogaster was monitored by measuring the; changes in the mean and variance of drive strength (in terms of “make” value); that occur in laboratory populations when SD and SD+ chromosomes are in; direct competition. The particular SD lines used are T(Y;Z),SD translocations; showing pseudo-Y drive. Four sets of population cages were analyzed. Two sets; were monitored for changes in SD fitness and drive strength (presumed to be; positively correlated) and analyzed for the presence of autosomal dominant; or X-linked modifiers after long periods of time. The remaining two sets were; made up of cages either made isogenic or variable for background genetic; material, and these were used to test whether the rate of accumulation of; modifiers was dependent on initial genetic variability.-Contrary to previous; studies in which most suppression of SD action could apparently be attributed; to a few dominantly acting modifiers of large effect, the conclusion here is; that laboratory populations that are initially free of such major dominant loci; evolve to suppress SD action by accumulating polygenic, recessive modifiers,; each of small effect, and that much of the required genetic variability can be; generated a!e novo by mutation. Possible explanations for these seemingly incompatible results and the evolutionary implications for SD are considered.
Transporting marker gene re (red eye) into a laboratory cage population of Aedes aegypti (Diptera Culicidae), using meiotic drive at MD locus
4486Wood, RJC, L. M.; Hamilton, A.; Whitelaw, A., Journal of Medical Entomology, 14:461-464. 1978-01-04 00:00:00.
An attempt has.been made to use the meiotic drive gene MD to transport a marker re (red eye) into a laboaratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the laboratory. The need for field estimates of fitness is indicated.
Sex ratio distortion caused by meiotic drive in a mosquito Culex pipiens
4485Sweeny, TLB, A. R., Genetics, 88:427-446. 1978-01-03 00:00:00.
A genetic factor, distorter (d), has been discovered that upsets the normal sex ratio of 1 : 1 and results in a large excess of males in Culex pipiens. The effect can be explained by a sex-linked, recessive gene. Males homozygous for the gene (Md/md) produce few female offspring; the effect is not due to postzygotic mortality. During the first meiotic division in spermatogenesis, the shortest chromosome pair, which, according to JOST and LAVEN (1971), is associated with sex determination, can be seen to be abnormal. In a high proportion of spermatocysts, one of the dyads of the shortest bivalent fragments, and the pieces are distributed irregularly to the daughter cells. It is believed that the female-determining chromosomes fragment. This would give rise to an excess of male-determining sperm. The possible usefulness of this factor for control or for experimental purposes is discussed.
Transporting marker gene re (red eye) into a laboratory cage population of Aedes-aegypti (Diptera Culicidae), using meiotic drive at MD locus
6233R. J. Wood, L. M. Cook, A. Hamilton and A. Whitelaw, Journal of Medical Entomology, 14:461-464. 1977-12-24 21:51:08.
An attempt has been made to use the meiotic drive gene MD to transport a marker re (redeye) into a laboratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the laboratory. The need for field estimates of fitness is indicated.
Experimental population-genetics of meiotic drive systems .1: Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster
4487Lyttle, TW, Genetics, 86:413-445. 1977-01-05 00:00:00.
The experimental population genetics of Y-chromosome drive in Drosophila; melanogasier is approximated by studying the behavior of T(Y;S),SD lines.; These exhibit “pseudo-Y” drive through the effective coupling of the Y chromosome; to the second chromosome meiotic drive locus, Segregation distorter; (SD). T(Y;S),SD males consequently produce only male offspring. When; such lines are allowed to compete against structurally normal SD+ flies in; population cages, T(Y;S),SD males increase in frequency according to the; dynamics of a simple haploid selection model until the cage population is; eliminated as a result of a deficiency in the number of adult females. Cage; population extinction generally occurs within about seven generatiomSeveral; conclusions can be drawn from these competition cage studies:; (1) Fitness estimates for the T(Y;Z),SD lines (relative to SD+) are generally; in the range of 2-4, and these values are corroborated by; independent estimates derived from studies of migration-selection; equilibrium.; (2) Fitness estimates are unaffected by cage replication, sample time, or; the starting frequency of T(Y;Z),SD males, indicating that data from; diverse cages can be legitimately pooled to give an overall fitness; estimate.; (3) Partitioning of the T(Y;S),SD fitnesses into components of viability,; fertility, and frequency of alternate segregation (Y + SD from; X+SD+) suggests that most of the T(Y;S),SD advantage derives; from the latter two components. Improvements in the system might; involve increasing both the viability and the alternate segregation to; increase the total fitness.; While pseudo-Y drive operates quite effectively against laboratory stocks,; it is less successful in eliminating wild-type populations which are already; segregating for suppressors of SD action. This observation suggests that further
Between family variation in sex-ratio in Trinidad (T-30) strain of Aedes-aegypti (L) indicating differences in sensitivity to meiotic drive gene MD
4494Wood, RJ, Genetica, 46:345-361. 1976-01-12 00:00:00.
Sex ratio in the Trinidad (T-30) strain of Aedes aegypti has remained constant at around 43%? during seventeen years of laboratory culture. The divergence from 50% is due to meiotic drive by the MD gene on the Y chromosome. The driving Y chromosome gives a much more distorted sex ratio (mean = 5.7%?) when coupled with the highly sensitive X chromosomes from strain 64. This was demonstrated in all of 98 families tested, indicating that all or most of the Y chromosomes in T-30 carry the MD gene. Consequently the low level of sex ratio distortion in T-30 must be due to resistance to MD.; ; Crosses made within T-30 demonstrated wide differences in sex ratio between families, depending on the sensitivity of the male parent's X chromosome to MD. However, sex ratios were not continuously variable but fell within fairly discrete categories. Thus, X chromosomes could be classified according to the modal sex ratios associated with them: ms3 (12.5%?), ms2 (32.5%?), ms1 (40%?), mr1 (47.5%?) mr2 (57.5%?).; ; The different sex ratio categories were more discrete in the families of sib matings than from random matings, suggesting the possibility of background modification of what is essentially a balanced polymorphism. Evidence is presented suggesting that the polymorphism could be due to interaction at two loci. A further X variant, ms4 (<10%?) characterised strain 64 but was absent from T-30.; ; A comparison of fertility between the different sex ratio categories in T-30 established that sex ratio distortion was not caused by differential mortality after fertilisation.
Population genetics of modifiers of meiotic drive.3. Equilibrium analysis of a gneral model for genetic control of segregation distortion
4493Thomson, GJF, M. W., Theoretical Population Biology, 10:8-25. 1976-01-11 00:00:00.
Prout, Bungaard and Bryant (1973, Theor. Popul. Biol. 4, 446–465) presented the first formal treatment of a model of meiotic drive involving a modifier locus which controls the intensity of drive. They studied the equilibrium behavior in the simplest model where it is assumed that drive is maximal when not suppressed. In that case there is one polymorphic equilibrium at which there is linkage disequilibrium. The equilibrium solutions in the general model of meiotic drive proposed by Prout, et al. are given in this paper together with a stability analysis. It is shown that up to three polymorphic equilibria may exist, two of which are in linkage disequilibrium and one in linkage equilibrium. These equilibria exhibit behavior qualitatively opposite to what is widely accepted as the usual for two locus systems and which is not seem in the simple case originally treated. The polymorphic equilibria with linkage disequilibrium may be stable for loose linkage and not for tight while that with linkage equilibrium is stable in an interval of relatively tight linkage values.
Evidence for autosomal meiotic drive in the butterfly Danaus chrysippus L.
4492Smith, DAS, Heredity, 36:139-142. 1976-01-10 00:00:00.
Danaus chrysippus (Danaidae) in East Africa is highly polymorphic for colour, the genetic control of which resides at three loci. The B locus has two alleles, B giving a nutbrown ground colour and bb orange on both fore and hindwings. The C locus determines forewing pattern: there are two alleles, C giving a wing uniformly coloured except for a black margin (form dorippus) and cc a large black apical area traversed by a row of white subapical spots (form ae&yptius = form chrysippus of my earlier papers). Heterozygotes (Cc) are basically dorippus but are often phenotypically distinct in showing the "aegyptius" subapical spots on the underside of the forewing. The B and C loci are closely linked (Smith, 1975a). The A locus has a recessive allele a the homozygous possessor of which has a large white patch on the hindwing (form alcippus when combined with the aegyptius forewing and form albinus with the dorippus forewing). The A locus probably assorts independently from the B and C loci (Clarke, Sheppard and Smith, 1973; Smith, 1975a). All-female broods commonly occur in D. chrysippus. These probably result when a Y-linked gene D causes meiotic drive for the Y chromosome so that it always enters the secondary oocyte at the first meiotic division in the female. Females from all-female broods usually themselves produce allfemale broods but a switch to bisexual broods can occur and seems to depend on the acquisition of a dominant autosomal suppressor gene S from the maternal male grandparent. The S locus is probably closely linked with the C locus (Smith, 1975b).
Modifier theory of meiotic drive: Is Mendelial segregation stable
4490Liberman, U, Theoretical Population Biology, 10:127-132. 1976-01-08 00:00:00.
The evolutionary fate of rare modifiers, based on the modifier theory of meiotic drive, is studied in this paper. It is shown that a polymorphism based on Mendelian segregation is never stable for any recombination frequencies between 0 and 12, and that, for tight linkage between the main locus and the modifier locus, the modifier locus tends towards heterozygosity.
Population genetics of modifiers of meiotic drive 4: Evolution of sex-ratio distortion
4497Thomson, GJF, M. W., Theoretical Population Biology, 8:202-211. 1975-01-15 00:00:00.
A model for the evolution of the sex-ratio meiotic drive system in Drosophila is proposed and analyzed. The model incorporates drive and altered fertility genetic modification The condition change in the sex-ratio of the modifying distortion overcome any relative of meiotic in the carriers of the modified sex-ratio chromosomes. that a sex-ratio modifying chromosome increase is that the relative fertility chromosome. When no fertility model predicts that any increase in distortion differences are involved, of the sex ratio will be favored. loss in carriers the
Sex-chromosome meiotic drive systems in Drosophila melanogaster .1: Abnormal spermatid development in males with a heterochromatin-deficient X-chromosome (sc4sc8)
4496Peacock, WJM, G. L. G.; Goodchild, D. J., Genetics, 79:613-634. 1975-01-14 00:00:00.
The meiotic drive characteristics of the In(1)sc4Lsc8R/Y system have been examined by genetic analysis and by light and electron microscopy. sc4sc8/Y males show a direct correlation between nondisjunction frequency and meiotic drive. Temperature-shift experiments reveal that the temperature-sensitive period for nondisjunction is at meiosis, whereas that for meiotic drive has both meiotic and post-meiotic components. Cytological analyses in the light and electron microscopes reveal failures in spermiogenesis in the testes of sc4sc8 males. The extent of abnormal spermatid development increases as nondisjunction becomes more extreme.
Modifier theory of meiotic drive
4495Hartl, DL, Theoretical Population Biology, 7:168-174. 1975-01-13 00:00:00.
The evolutionary fate of rare modifiers of recessive lethal segregation distorters has been studied. Suppressors or partial suppressors will always increase in frequency. Enhancers will increase in frequency if linkage is sufficiently tight and be lost if linkage is sufficiently loose.
Sex-ration, meiotic drive, and group selectin in Drosophila pseudoobscura
4498Policansky, D, American Naturalist, 108:75-90. 1974-01-16 00:00:00.
Sex ratio (SR) is a widespread genetic condition of the X-chromosome in Drosophila species which causes males to produce progenies consisting almost entirely of females. Results of samples from natural populations of Drosophila pseudoobscura and results of some laboratory experiments indicate that SR males produce only about half as many sperm as normal (ST) males; because of this deficiency, SR males are able to fertilize only about half as many eggs as ST males. These results explain the observed equilibria of frequencies of SR in natural populations, and suggest that, at least in the case of D. pseudoobscura, male fertility may be partly limited by the number of sperm males can produce.
Multiple meiotic drive systems in Drosophila melanogaster male
4499Miklos, GLGY, A. F.; Peacock, W. J., Genetics, 72:105-115. 1972-01-17 00:00:00.
The behaviour of two "meiotic drive" systems, Segregation-Distorter (SD) and the sex chromosome sc4sc8 has been examined in the same meiocyte. It has been found that the two systems interact in a specific way. When the distorting effects of SD and sc4sc8 are against each other, there is no detectable interaction. Each system is apparently oblivious to the presence of the other, gametes being produced according to independence expectations. However when the affected chromosomes are at the same meiotic pole an interaction occurs; the survival probability of the gamete containing both distorted chromosomal products is increased, rather than being decreased by the combined action of two systems.
Mechanisms of meiotic drive
4502Zimmering, SS, L.; Nicoletti, B., Annual Review of Genetics, 4:409-436. 1970-01-20 00:00:00.
Meiotic drive has been defined by Sandler & Novitski (157) as any alteration of the normal process of meiosis with the consequence that a heterozygote for two genetic alternatives produces an effective gametic pool with an excess of one type; such a pattern of behavior will drastically alter the frequency of alleles in a population in such a way that a driven allele may increase in frequency in spite of deleterious physiological effects. This general concept has, however, been taken to include transmissional anomalies that are not strictly meiotic, but with similar populational consequences [see, for example, Lewontin (93)]; this extended meaning seems justified and thus the more general definition will be used in this review.
Meiotic drive in natural populations of Drosophila melanogaster 9: Suppressors of segregation distorter in wild populations
4500Hartl, DL, Canadian Journal of Genetics and Cytology, 12:594-600. 1970-01-18 00:00:00.
A population of Drosophila melanogaster in Madison, Wisconsin, has been screened for suppressors of segregation distorter (SD), an autosomal meiotic drive element found in the same population. Three kinds of suppressors were tested for: (1) Y-linked suppressors, none were found, (2) X-linked suppressors, whose frequency was found to be 85%, and (3) autosomal dominant suppressors, which occur in 45% of autosome complements.The frequency of X-linked suppressors is comparable to that found in a Japanese population; autosomal suppressors are much more frequent in Madison than in Japan (Katoaka, 1967). The similarity in the frequency of sex-linked suppressors may result from the meiotic drive shown by the suppressor-X itself; the difference in the frequency of autosomal dominant suppressors is possibly related to a higher frequency of SD itself in the Madison population.
Meiotic drive and visible polarity in Drosophila spermatocytes
4504Yanders, AFB, J. G.; Peacock, W. J.; Goodchild, D. J., Genetics, 59:245-253. 1968-01-02 00:00:00.
The model for meiotic drive presented by PEACOCK and ERICKSON (1965) demands that an intracellular differentiation exists at the time of the first meiotic division in spermatocytes. As a result of this differentiation, one of the spindle poles at anaphase I will lead to the formation of two functional sperm, while the other pole will yield two nonfunctional sperm. This model can be used to explain cases of meiotic drive, such as Segregation-Distorter (SD) ( SANDLER, HIRAIZUMI, and SANDLER 1959), if one member of a chromosome pair moves to the functional pole in a nonrandom fashion, and is thereby preferentially included in the functional gametes.
Extraordinary sex ratios
6186W. D. Hamilton, Science, 156:477-488. 1967-04-03 19:10:19.
The two sexes are usually produced in approximately equal numbers. Fisher (1) was the first to explain why, under natural selection, this should be so, irrespective of the particular mechanism of sex determination. His rather tersely expressed argument has been clarified by subsequent writers (2) and seems to be widely accepted. In bare outline, the factor of parental care being ignored, it may be given as follows: 1) Suppose male births are less common than female. 2) A newborn male then has better mating prospects than a newborn female, and therefore can expect to have more offspring. 3) Therefore parents genetically disposed to produce males tend to have more than average numbers of grandchildren born to them. 4) Therefore the genes for male-producing tendencies spread, and male births become commoner. 5) As the 1:1 sex ratio is approached, the advantage associated with producing males dies away. 6) The same reasoning holds if females are substituted for males throughout. Therefore 1:1 is the equilibrium ratio.
Meiotic drive in Drosophila involving chromosome breakage
4506Erickson, J, Genetics, 51:555-571. 1965-01-04 00:00:00.
In ordinary genetic systems the members of a pair of unlike alleles, or of a pair of unlike chromosomes, are recovered in equal numbers among the off spring, barring complications affecting viability. Contrary to this expectation, in a number of studies it has been found that one allele or chromosome is recovered in significantly more than 50 percent of the functional gametes. The time and mode of the action resulting in inequality varies; where these phenomena result from events of the meiotic process they are known as instances of meiotic drive (SANDLER and NOVITSKI 1957). The case described herein was isolated from a chronically irradiated population (NOVITSKI and HANKS 1961), and was referred to as “29G” previously (HANKS 1961; ERICKSON and HANKS 1961). HANKS (1964) has renamed the line “RD”, referring to a disruption in recovery of the Y chromosome. which gives rise to a high-female sex ratio in the off spring of RD males.
Aanalysis of case of meiotic drive in Drosophila melanogaster
4507Hanks, GD, Genetics, 50:123-130. 1964-01-05 00:00:00.
IN the past ten years there has been a renewed interest in the abnormal recovery of chromosomes after meiosis; see for example DUNN (1953); NOVITSKI and SANDLER (1957) ; SANDLER and NOVITSKI ( 1957) ; LINDSLEY and SANDLER (1958); NOVITSKI and HANKS (1961); and MAGUIRE (1963). When the two types of gametes from a heterozygote are recovered with unequal frequency because of a meiotic mechanism the force resulting is called meiotic drive (SANDLER and NOVITSKI 1957). Such a force is capable of altering allele frequencies in a population, and thus the evolutionary consequences are potentially important; this has been discussed in detail by DUNN (1953) and SANDLER and NOVITSKI (1957). The case analyzed here was found by testing chromosomes from population cages maintained by WALLACE atCold Spring Harbor which were subjected to low intensity radiation for over 200 generations (WALLACE 1956). Earlier studies have indicated that the case here analyzed does not produce its effect by zygotic mortality, is manifested only in the male, and is greatly altered by temperature changes during the period of meiosis in the male (NOVITSKI and HANKS 1961; ERICKSON and HANKS 1961). This paper presents the genetic analysis of this case showing the extent to which its effect may be modified by substituting different sex chromosomes and autosomes.
On the role of lethal mutants in the control of populations
6101R. C. Von Borstel and A. A. Buzzati-Traverso, Radioisotopes and Radiation in Entomology: Proceedings of a Symposium, Bombay, 5-9 December, 1960, 1962:273-278. 1962-01-02 16:52:59.
On the role of lethal. mutants in the control of populations. Population control by release of irradiated males requires that the sperm must be damaged by radiation. The type of damage induced by radiation imposes a restriction on which species may be controlled because if the sperm are functionally damaged by radiation, then for effective control, the females must be monogamous. If dominant lethality is induced in sperm then either polygamy or monogamy may prevail. It is generally accepted that dominant lethal events are induced in sperm at doses much lower than those required to hamper sperm function or cause sperm inactivation. With Drosophila it is possible to test directly the effect of releasing irradiated males into an artificial population where polygamy is the rule. Preliminary experiments have been performed under conditions of unlimited production of offspring. It appears that radiation induces dominant lethality in sperm, and the sperm that bear dominant lethals are able to compete successfully with normal sperm. A series of tests are currently under way to ascertain the degree of induced dominant lethality and sperm inactivation at different X-ray dosages. A series of experiments are outlined in a general discussion of the possible use of dominant and recessive lethals for bringing about collapse of artificial and natural populations.
Meiotic drive in natural populations of Drosophila melanogaster .7. Conditional segregation distortion – a possible nonallelic conversion
4512Sandler, LH, Y., Genetics, 46:585-604. 1961-01-10 00:00:00.
Males, heterozygous for the Segregation-distorter (SD) allele (located in or near the centromeric heterochromatin of the right arm of chromosome 11) and a standard tester second chromosome, regularly produce a preponderance of functional SD-bearing sperm ( SANDLER, HIRAIZUMI and SANDLER 1959). Segregation in heterozygous SD females, on the other hand, is always normal. It has been found, however, that, for certain SD lines, if the SD-bearing chromosome is inherited from the female parent, then, in a fraction of F, male sibships, only one half of the heterozygous SD sons exhibit the phenomenon of segregationdistortion; in the other half of the sons, segregation is normal. In the following generation, all of the males exhibit abnormal ratios irrespective of whether or not their father showed an abnormal ratio. Those females that produce sons. only one half of which distort, are referred to as conditioned; the phenomenon is termed conditional distortion ( SANDLER and HIRAIZUMI 1959)
Meiotic drive in natural populations of Drosophila melanogaster .8. A heritable aging effect on phenomenon of segregation distortion
4511Sandler, LH, Y., Canadian Journal of Genetics and Cytology, 3:34-46. 1961-01-09 00:00:00.
Second chromosomes have been found in natural populations of Drosophila melanogaster that contain an abnormal centromere region which conditions a highly aberrant segregation ratio in heterozygous males (Sandler, Hiraizumi, and Sandler, 1959). In particular, when a chromosome carrying this abnormal region (symbolized SD for Segregation-distorter) is made heterozygous with a normal second chronlosome (routinely a standard tester chromosome marked by the recessives cn and bw) in males, and backcrossed to homozygous cn bw females, 90 per cent or more of the F1 receive the SD-bearing second chromosome. These abnormal segregation ratios are not accompanied by egg mortality. It has now, been found that as heterozygous SD males are aged, the segregation ratios become less abnormal. When, moreover, young sons of aged fathers are examined, it is found that they too exhibit less extreme segregation ratios. Indeed, changes in the segregation ratio induced by aging may persist in selected, males for at least five generations and possibly indefinitely. The evidence demonstrating a heritable aging effect and a consideration of certain other questions relevant to the aging phenomenon are presented below.
Analysis of irradiated Drosophila populations for meiotic drive
4510Novitski, EH, G. D., Nature, 190:989-990. 1961-01-08 00:00:00.
The existence of chromosomes or alleles that are represented in the gametes of a heterozygote with a frequency greater than the expected 50 percent is now well established for a variety of species. The immediate population result of introducing such a chromosome or allele must be a sharp increase in its frequency, alon with any other genes associated by linkage, independent of or, indeed, in spite of, their phenotypic effects. For this reason such phenomena have been referred to as cases of 'drive' and, more specifically, as 'meiotic drive' when the basis is found in some aberration of meiosis. Such instances would seem to provide an unparalleled opportunity for the study of population dynamics, for example, the efficacy of response of natural selection to unfavourable genes. It seemed worth while, therefore, to determine whether such chromosomes or alleles characterized by drive might be induced in the laboratory.
Meiotic drive in natural populations of Drosophila melanogaster .6: A preliminary report on presence of segregation-distortion in a Baja california population
4509Mange, EJ, American Naturalist, 95:87-96. 1961-01-07 00:00:00.
Meiotic drive is a term coined by Sandler and Novitski (1957) to describe; the situation whereby a heterozygote produces gametes containing an excess; of one allele, rather than the expected equality. As a consequence of such; aberrant segregations, gene frequencies within a population may be radically; altered; indeed, detrimental or lethal genes closely linked to the driven gene; may increase in frequency, thereby leading to a reduction in fitness or pos; sibly even to extinction of the population.; An instance of meiotic drive in Drosophila melanogaster, discovered by; Hiraizumi in a Madison, Wisconsin, population, has been reported by Sandler,; Hiraizumi and Sandler (1959). The phenomenon, termed segregation-distortion,; was found to depend upon a locus designated SD, which is located in the; centromeric heterochromatin of chromosome II. The phenomenon is ex; pressed in males only.; Since segregation-distortion was originally found in a natural population,; the question arose as to whether the phenomenon is of recent origin and; therefore localized in the vicinity of Madison, or well established and hence; widespread among natural populations of Drosophila melanogaster. There; fore, the screening of wild populations for SD (or for any other type of aber; rant segregation) was undertaken. In small samples from only thirteen popu; lations, SD has been detected in one Baja California population as well as; in three other rather widely separated Madison populations. This report will; be confined to establishing that the locus discovered in the southern Cape; region of Baja California (specifically, from Rancho La Burrera near the; west base of Sierra de La Laguna, and a Pleistocene lake relic, called; La Laguna, in the same range) is indeed SD.
Time of temperature sensitivity of meiotic drive in Drosophila melanogaster
4508Erickson, JH, G. D., American Naturalist, 95:247-250. 1961-01-06 00:00:00.
In a line of Drosophila melanogaster demonstrating meiotic drive, it was found that the high recovery rate of the X-chromosome could be nearly nullified by temperature treatment. A series of experiments were carried out to determine at what stage of the life-cycle this treatment is effective. The effect is observed to occur during a part of the process of spermatogenesis, either during the primary spermatocyte stage or extending through this and the meiotic divisions which follow.
Meiotic drive in natural populations of Drosophila melanogaster .4: Instability at the Segregation Distorter locus
4515Sandler, LH, Y., Genetics, 45:1269-1287. 1960-01-13 00:00:00.
In a collection of flies from a natural population of Drosophila melanogaster, several second chromosomes have been isolated that contain, in the centromere region .of chromosome 11, a locus (named segregation-distorter and symbolized SO) that conditions, in heterozygous males, a highly abnormal segregation ratio in favor of the SD-bearing chromosome. Experiments bearing on the cytogenetic basis of the phenomenon of segregation-distortion and on the formal genetics of the SD locus have been reported by SANDLER, HIRAIZUMI, and SANDLER (1959). and by SANDLER and HIRAIZUMI ( 1959).
Meiotic drive in natural populations of Drosophila melanogaster .5. On the nature of the SD region
4514Sandler, LH, Y., Genetics, 45:1671-1689. 1960-01-12 00:00:00.
Second chromosomes were collected from nature which, when heterozygous with a normal chromosome 1 in males, are present in functional sperm much more often than the expected 50 percent. This phenomenon, named segregation distortion, was found to depend on a locus named Segregation-distorter (symbolized SD), which is located near the centromere (and probably in the right arm) of chromosome 1
Meiotic drive in natural-populations of Drosophila melanogaster 3: Populational implications of the Segregation-Distorter locus
4513Hiraizumi, YS, L.; Crow, J. E., Evolution, 14:433-444. 1960-01-11 00:00:00.
If, among the successful gametes frm heterozygotes, one allele is regularly included in more than half, it may increase in frequency even if it has a harmful effect. Unequal gamete production, when attributable to the mechanics of meiosis, has been called meiotic drive (Sandler and Novitski, 1957). An example is segregation-distortion in Drosophila melanogaster, the cytogenetic behavior of which has been reported by Sander, Hiraizumi and Sandler (1959) and Sandler and Hiraizumi (1959)
Meiotic drive in natural populations of Drosophila melanogaster .1. The cytogenetic basis of segregation distortion
4517Sandler, LH, Y.; Sandler, I., Genetics, 44:233-250. 1959-01-15 00:00:00.
Meiotic drive has been defined as a force, potentially capable of altering gene frequencies in natural populations, which somehow depends upon the nature of the meiotic divisions; specifically, when the meiotic divisions are such that the two kinds of gametes from a heterozygote are produced in a ratio different from 1 : 1 ( SANDLER and NOVITSKI 195 7). There have been reported numerous cases which either are, or may be, examples of meiotic drive. These include cases in Drosophila ( GERSHENSON 1928; STURTEVANT and DOBZHANSKY 1936; NOVITSKI 1951 ; NOVITSKI and IRIS SANDLER 1957; LINDSLEY and SANDLER 1958), in maize (RHOADES 1942; LONGLEY 1945), in tobacco (CAMERON and MOAV 1957), and possibly in mice (DUNN 1953) and in man (DUNN 1953; SANDLER and NOVITSKI 1957). The purpose of this paper is to present a first account of the results of a series of studies designed to elucidate the cytogenetic basis of a case of meiotic drive which was discovered in a natural population of D. melanogaster. In this population there has been found a second chromosome locus, located in or near the proximal heterochromatin and called segregation-distorter (symbol, SO), which is recovered much more frequently than its normal allele among the progeny of heterozygous male parents. This phenomenon, to which the name segregation distortion has been applied, (1) has never been found to occur in females, (2) apparently requires synapsis (particularly in the region of the locus in question) in order to operate, and (3) comes about as a result of the failure of sperm carrying the normal allele to be formed or to function normally. The evidence bearing on these, and certain other points, and a cytogenetic model to account for the results are presented below.
Meiotic drive in natural populations of Drosophila melanogaster 2. Genetic variation at the Segregation Distorter locus
4516Sandler, LH, Y., Proceedings of the National Academy of Sciences of the United States of America, 45:1412-1422. 1959-01-14 00:00:00.
It has now been found that the proportion of heterozygous SD males resulting from any given cross which exhibits segregation-distortion, and the amount of distortion that any particular male shows (the k value), varies widely depending upon the precise source and history of the SD-bearing and the SD+-bearing chromosomes in the heterozygotes being tested. It is the purpose of this report to present a general account of the kinds of variations in the behavior of SD which have been observed. More fully documented reports of each phase of the work are currently in preparation, and will be presented elsewhere. For this reason, extended discussion of these variations and comparable systems in other organisms has been omitted.
Meiotic drive as an evolutionary force
4518Sandler, L. and Novitski, E., American Naturalist, 91:105-110. 1957-01-16 00:00:00.
A heterozygote for alleles A and A' ordinarilly produces gametes carrying each of the alleles with a frequency of 50 per cent. The constancy of allele frequencies from one generation to the nest in natural populations of diploid species depends on this equality, which itself depends on the nature of the meiotic divisions. As the study of the genetics of higher organisms becomes more precise and extensive, an increasing number of cases is found in which heterozygotes of certain constitutions fail to produce the two kinds of gametes with equal frequency. Such a pattern of behavior will drastically alter frequencies of alleles in a population; where such a fouce, potentially capable of altering gene frequencies, is a consequence of the mechanics of the meiotic divisions, we suggest that the name meiotic drive be applied. The distinction between meiotic drive and the superficially similar phenomenon of gametic selection and gametic competition may be operationally difficult in those instances in which a detailed cytogenetic study cannot be made. The later, however, represent selecdtion in the ordinary sense, operating in the haploid phase, and as such their effectiveness is directly dependent on the gene content (fitness) of the gametes, whereas the effectiveness of the former is independent of the gene content in the ordinary sense.
Inheritance in Nicotiana tabacum XXVII. Pollen Killer, An alien genetic locus inducing abortion of microspores not carrying it
6116D. R. Cameron and R. M. Moav, Genetics, 42:326. 1957-01-02 19:37:02.
A cytogenetic study of experimental introgression from N. plumbaginifolia (pbg) into N. tabacum (tbc) has been pursued in this laboratory for several years (CLAUSEN 1952). In the hybrid derivatives it was observed that genically controlled pollen abortion was associated with the addition of a pbg chromosome to the tbc complement. This chromosome also carried the locus (Bs) determining resistance or probably immunity to black shank, a serious disease of commercial tobacco caused by Phytophthora parasitica var. nicotianae. (For description see CLAYTON and AICAIVRTRY 1950). Paradoxically, it developed that the pbg chromosome under study produced its effect on gametophytes in which it was not present. Thus, the male gametophytes containing a complete set of 24 tbc chromosomes degenerate while most of the functional pollen had the constitution 24 tbc + 1 pbg. This paper presents a description of the genetic aspects of the problem with some suggestions as to the possible method of action of the locus involved. Certain other phases of the larger investigation will be mentioned but only as they apply to the pollen lethal condition. The investigation was initiated by the late PROF. R. E. CLAUSEN who participated actively in the work presented here.
Preferential segregation in maize
6000M. M. Rhoades, Genetics, 27:395-407. 1942-12-30 19:47:18.
An abnormal type of chromosome 10, found by Longley in maize from the s.-w. part of the U. S., is preferentially segregated during megasporogenesis. More than 70% of the ovules receive the abnormal chromosome instead of the 50% expected with random segregation. At pachytene the length of the extra piece of chromatin in the abnormal chromosome is slightly greater than the short arm of chromosome 10. The proximal and distal portions of the extra piece are euchromatic, but a large and conspicuous knob lies between the 2 euchromatic portions. The origin of this extra piece is unknown. Pollen with the abnormal chromosome 10 is only partially successful in competing with pollen possessing a normal chromosome 10. Extra chromatin present in the abnormal chromosome may impair pollen-tube growth. The excess of ovules with the abnormal type of chromosome is due neither to abortion of ovules with a normal chromosome nor to megaspore competition. The R locus, known to lie in the long arm of chromosome 10, proved to be closely linked to the extra piece of chromatin which is believed to be inserted near the tip of the long arm. The observed % of recombination (1-2%) is probably less than the amt. occurring distal to R in stocks carrying 2 normal chromosomes 10. Crossing-over in the gR region is not affected when the abnormal chromosome is heterozygous, and crossing-over in this interval did not affect preferential segregation. Evidence was obtained indicating the influence of the environment on the degree of preferential segregation.
A new sex-ratio abnormality in Drosophila obscura
6047S. Gershenson, Genetics, 13:488. 1928-12-30 21:32:10.
1. The sex-ratio in the normal lines of Drosophila obscura is very near to the theoretical 1 : 1. 2. Out of 19 females caught in nature, two were heterozygous for a gene which causes strong deviations in the normal sex distribution. 3. The researches made have shown that this gene is localized in the X-chromosome and is transmitted like an ordinary sex-linked gene. 4. This gene is absolutely sex-limited, as it is not manifested either in heterozygous or homozygous females. 5. The males bearing this gene give in their progeny about 96 percent of females and only about 4 percent of males. 6. This gene has no influence on the development of the zygotes already formed, but acts directly upon the mechanism of sex-distribution. It provokes a sharp preponderance of females by almost totally removing the spermatozoa with the Y-chromosome from the fertilization process, acting thus like a gametic lethal (in the genetic sense of this term).
Sur la reproduction des souris anoures
6057N. Dobrovolskaia-Zavadskaia and N. Kobozieff, Comptes rendus des séances de la Société de biologie et de ses filiales, 97:116-119. 1927-06-15 15:44:03.
Nous ne connaissons que deux lignees de Souris sans queue, celle de Lang (1913), et cell de Duboscq (1922). L’elevange de Lang (lignee des Souris brachyures et anoures du preparateur Alfred Nageli) a donne 199 Souris normales, pour 173 brachyures et 9 anoures. Croisses entre ells et aveec des bachyures, les Souris anoures n’ont donne aucune reproduction. Dans la lignee du P Duboscq, provenant d’une femelle anoure A et de son frere normal, et comportant 25 petis en 8 portees, il y avait 8 anoures, don’t la plupart moururent jeunes.
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