Keywords: Evolution
Selfish sperm hijack Overdrive gene to kill healthy rivals
35511Lisa Potter, Phys.org, 2026-03-12 15:14:08.
A new University of Utah-led study has discovered the mechanism behind a decades-old evolutionary mystery—how "selfish chromosomes" cheat the rules of genetic inheritance. The researchers found that rogue chromosomes hijack the Overdrive (Ovd) gene to destroy rival sperm. The study is the first to identify that the Ovd gene acts as a quality control checkpoint during sperm development. Normally, Ovd detects and eliminates abnormal sperm cells. But selfish chromosomes exploit the system to kill competitors, boosting their chances of passing into the next generation. The findings, published in Nature Communications, reveal the biology behind segregation distortion, a phenomenon in which genes sway inheritance in their favor to beat the standard 50/50 odds predicted by Mendelian genetics. The team observed the scheme in two Drosophila species, each carrying completely different selfish chromosomes, which suggests that multiple genetic systems may evolve independently to exploit the same Ovd pathway.
The Evolutionary Genomics of Meiotic Drive
35407Daven C Presgraves, R Kelly Dawe, Kelly A Dyer, et al., Molecular Biology and Evolution, 2026-01-23 16:40:29.
Meiotic drivers are selfish genetic elements that gain transmission advantages by distorting equal, Mendelian segregation. For decades, biologists have considered meiotic drivers as interesting, albeit esoteric, case studies. It is now clear, however, that meiotic drive is more common and phylogenetically widespread than previously supposed. Indeed, intensive study of a few well-known cases has begun to reveal the evolutionary genomic consequences of meiotic drive. We argue here that many features of genome evolution, content, and organization that are seemingly inexplicable by organismal adaptation or nearly neutral processes are instead best accounted for by recurrent histories of meiotic drive. We review how meiotic drive can affect the evolution of sequences, gene copy numbers, genes with functions in meiosis and gametogenesis, signatures of “selection”, chromosome rearrangements, and karyotype evolution. We also explore the interactions of meiotic drive elements with other classes of selfish genetic elements, including satellite DNAs, transposable elements, and with the endogenous host genes involved in drive suppression. Finally, we argue that some aspects of drive-mediated genome evolution are now sufficiently well established that we might reverse the direction of discovery— rather than ask how drive affects genome evolution, we can use genome data to discover new putative drive elements.
Drive, suppression and escape from suppression of a selfish chromosome
35382Jackson Ridges, Jackson Bladen, Robert Unckless, Nitin Phadnis, Proc Biol Sci, 21. 2026-01-21 13:39:59.
Meiotic drivers are selfish genetic elements that are predicted to spark rapid intra-genomic arms races with their suppressors. However, the long-term persistence of unsuppressed selfish chromosomes in natural populations violates these theoretical expectations. The Drosophila pseudoobscura Sex-Ratio (SR) chromosome exemplifies this problem, sometimes referred to as the ‘ancient gene drive paradox’. Here, we analyse the evolutionary history of this SR chromosome and show that its genetic architecture and complexity have likely been shaped by a history of drive, suppression and escape from suppression. Our results suggest that the current lack of resistance to the SR chromosome may represent a transient condition awaiting the emergence of new suppressors.
Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae
35231Smidler, A.L., Marrogi, E.A., Scott, S. et al., Scientific Reports, 15. 2025-10-09 10:19:39.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing and functional r1 alleles permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired putative haplolethal-haplosufficient (Ribosome–Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants in the process reveal a major lethality and infertility hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for development of future gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.
Anticipating evolutionary responses of mosquito mating systems to population suppression with mass-reared males
34745Bonsall, M.B., Cator, L.J., Current Opinion in Insect Science, 68. 2025-04-06 19:52:32.
Strategies that rely on the mass release of males to suppress mosquito populations will exert selective pressure on natural mating systems. Here, we investigate how mass releases might affect the mating behaviors of wild target populations. We highlight gaps in our understanding of both variation in these aspects of mosquito behavior and the evolutionary forces that maintain variation within and between populations. We provide a mathematical framework for integrating mosquito mating ecology into models of population suppression. Given that these strategies are being increasingly deployed, anticipating and managing evolutionary responses of target population behavior should be a priority for research.
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.
Teosinte Pollen Drive guides maize diversification and domestication by RNAi
34650Berube, B., Ernst, E., Cahn, J. et al., Nature, 633:380-388. 2024-08-07 06:59:44.
Selfish genetic elements contribute to hybrid incompatibility and bias or ‘drive’ their own transmission1,2. Chromosomal drive typically functions in asymmetric female meiosis, whereas gene drive is normally post-meiotic and typically found in males. Here, 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 (Z. mays ssp. mexicana) that depends on RNA interference (RNAi). 22-nucleotide 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 Americas3, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize4. A survey of maize traditional varieties and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least four chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive probably had a major role in maize domestication and diversification, and offers an explanation for the widespread abundance of ‘self’ small RNAs in the germ lines of plants and animals.
Rapid turnover of pathogen-blocking Wolbachia and their incompatibility loci
28733Shropshire JD, Conner WR, Vanderpool D, Hoffmann AA, Turelli M, Cooper BS., bioRxiv, 2023-12-19 16:02:29.
At least half of all insect species carry maternally inherited Wolbachia alphaproteobacteria, making Wolbachia the most common endosymbionts in nature. Wolbachia spread to high frequencies is often due to cytoplasmic incompatibility (CI), a Wolbachia -induced sperm modification that kills embryos without Wolbachia . Several CI-causing Wolbachia variants, including w Mel from Drosophila melanogaster , also block viruses. Establishing pathogen-blocking w Mel in natural Aedes aegypti mosquito populations has reduced dengue disease incidence, with one study reporting about 85% reduction when w Mel frequency is high. However, w Mel transinfection establishment is challenging in many environments, highlighting the importance of identifying CI-causing Wolbachia variants that stably persist in diverse hosts and habitats. We demonstrate that w Mel-like variants have naturally established in widely distributed holometabolous dipteran and hymenopteran insects that diverged approximately 350 million years ago, with w Mel variants spreading rapidly among these hosts over only the last 100,000 years. Wolbachia genomes contain prophages that encode CI-causing operons ( cifs ). These cifs move among Wolbachia genomes - with and without prophages - even more rapidly than Wolbachia move among insect hosts. Our results shed light on how rapid host switching and horizontal gene transfer contribute to Wolbachia and cif diversity in nature. The diverse w Mel variants we report here from hosts present in different climates offer many new options for broadening Wolbachia -based biocontrol of diseases and pests.
Upper Bound on the Mutational Burden Imposed by a CRISPR-Cas9 Gene-Drive Element
28722Michael S. Overton, Sean E. Guy, Xingsen Chen, Alena Martsul, Krypton Carolino, Omar S. Akbari, Justin R. Meyer, Sergey Kryazhimskiy, bioRxiv, 2023-12-19 12:04:20.
CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To estimate how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae. Despite its substantial statistical power, our experiment revealed no detectable effect of CCGD or Cas9 alone on the genome-wide rates of mutations or LOH events, suggesting that these rates are affected by less than 30%. Nevertheless, we found that Cas9 caused a slight but significant shift towards more interstitial and fewer terminal LOH events, and the CCGD caused a significant difference in the distribution of LOH events on Chromosome V. Taken together, our results show that these genetic elements impose a weak and likely localized additional mutational burden in the yeast model. Although the mutagenic effects of CCGDs need to be further evaluated in other systems, our results suggest that the effect of CCGDs on off-target mutation rates and genetic diversity may be acceptable.
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.
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.
Wolbachia has subtle effects on thermal preference in highly inbred Drosophila melanogaster which vary with life stage and environmental conditions
27676A. Strunov, C. Schoenherr and M. Kapun, Scientific Reports, 13:13792. 2023-08-23 07:09:52.
Temperature fluctuations are challenging for ectotherms which are not able to regulate body temperature by physiological means and thus have to adjust their thermal environment via behavior. However, little is yet known about whether microbial symbionts influence thermal preference (Tp) in ectotherms by modulating their physiology. Several recent studies have demonstrated substantial effects of Wolbachia infections on host Tp in different Drosophila species. These data indicate that the direction and strength of thermal preference variation is strongly dependent on host and symbiont genotypes and highly variable among studies. By employing highly controlled experiments, we investigated the impact of several environmental factors including humidity, food quality, light exposure, and experimental setup that may influence Tp measurements in adult Drosophila melanogaster flies. Additionally, we assessed the effects of Wolbachia infection on Tp of Drosophila at different developmental stages, which has not been done before. We find only subtle effects of Wolbachia on host Tp which are strongly affected by experimental variation in adult, but not during juvenile life stages. Our in-depth analyses show that environmental variation has a substantial influence on Tp which demonstrates the necessity of careful experimental design and cautious interpretations of Tp measurements together with a thorough description of the methods and equipment used to conduct behavioral studies.
Fighting the battle against evolution: designing genetically modified organisms for evolutionary stability
28008M. Arbel-Groissman, I. Menuhin-Gruman, D. Naki, S. Bergman and T. Tuller, Trends in Biotechnology, 2023-07-12 06:48:15.
Synthetic biology has made significant progress in many areas, but a major challenge that has received limited attention is the evolutionary stability of synthetic constructs made of heterologous genes. The expression of these constructs in microorganisms, that is, production of proteins that are not necessary for the organism, is a metabolic burden, leading to a decrease in relative fitness and make the synthetic constructs unstable over time. This is a significant concern for the synthetic biology community, particularly when it comes to bringing this technology out of the laboratory. In this review, we discuss the issue of evolutionary stability in synthetic biology and review the available tools to address this challenge
Steering and controlling evolution — from bioengineering to fighting pathogens
26463M. Lässig, V. Mustonen and A. Nourmohammad, Nature Reviews Genetics, 2023-07-03 07:31:07.
Control interventions steer the evolution of molecules, viruses, microorganisms or other cells towards a desired outcome. Applications range from engineering biomolecules and synthetic organisms to drug, therapy and vaccine design against pathogens and cancer. In all these instances, a control system alters the eco-evolutionary trajectory of a target system, inducing new functions or suppressing escape evolution. Here, we synthesize the objectives, mechanisms and dynamics of eco-evolutionary control in different biological systems. We discuss how the control system learns and processes information about the target system by sensing or measuring, through adaptive evolution or computational prediction of future trajectories. This information flow distinguishes pre-emptive control strategies by humans from feedback control in biotic systems. We establish a cost–benefit calculus to gauge and optimize control protocols, highlighting the fundamental link between predictability of evolution and efficacy of pre-emptive control.
What should we call evolution driven by genetic engineering? Genetic welding, says researcher
24897Cell Press, Phys Org, 2023-03-28 07:29:32.
With CRISPR-Cas9 technology, humans can now rapidly change the evolutionary course of animals or plants by inserting genes that can easily spread through entire populations. Evolutionary geneticist Asher Cutter proposes that we call this evolutionary meddling “genetic welding.” In an opinion paper publishing March 28 in the journal Trends in Genetics, he argues that we must scientifically and ethically scrutinize the potential consequences of genetic welding before we put it into practice.
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.
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.
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.
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'.
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.
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.
Rescue by gene swamping as a gene drive deployment strategy
20587K. D. Harris and G. Greenbaum, bioRxiv, 2022.03.08.483503. 2022-03-08 11:25:49.
Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.Competing Interest StatementThe authors have declared no competing interest.
Cytoplasmic incompatibility in hybrid zones: infection dynamics and resistance evolution
19742E. S. Røed and J. Engelstädter, Journal of Evolutionary Biology, 2021-12-25 13:16:15.
Cytoplasmic incompatibility is an endosymbiont-induced mating incompatibility common in arthropods. Unidirectional cytoplasmic incompatibility impairs crosses between infected males and uninfected females, whereas bidirectional cytoplasmic incompatibility occurs when two host lineages are infected with reciprocally in compatible endosymbionts. Bidirectional cytoplasmic incompatibility is unstable in unstructured populations, but may be stable in hybrid zones. Stable coexistence of incompatible host lineages should generate frequent incompatible crosses. Therefore, hosts are expected to be under selection to resist their endosymbionts. Here, we for mulate a mathematical model of hybrid zones where two bidirectionally incompatible host lineages meet. We expand this model to consider the invasion of a hypothetical resistance allele. To corroborate our mathematical predictions, we test each prediction with stochastic, individual-based simulations. Our models suggest that hybrid zones may sustain stable coinfections of bidirectionally incompatible endosymbiont strains. Over a range of conditions, host are under selection for resistance against cytoplasmic incompatibility. Under asymetric migration, a resistance allele can facilitate infection turnover and subsequently either persist or become lost. The predictions we present may inform our understanding of the cophylogenetic relationship between the endosym biont Wolbachia and its hosts.
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.
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.
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.
Genetic pest management and the background genetics of release strains
15695P. T. Leftwich, L. G. Spurgin, T. Harvey-Samuel, C. J. E. Thomas, L. C. Paladino, M. P. Edgington and L. Alphey, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190805. 2020-12-28 15:35:20.
We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti
15689N. A. Ahmad, M.-V. Mancini, T. H. Ant, J. Martinez, G. M. R. Kamarul, W. A. Nazni, A. A. Hoffmann and S. P. Sinkins, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190809. 2020-12-28 15:06:28.
Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands.
Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex
15277S. Dhole, A. L. Lloyd and F. Gould, Annual Review of Ecology, Evolution, and Systematics, 51:505-531. 2020-08-28 21:09:09.
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theoretical possibility, gene drive spread in natural populations is more complex and merits a more realistic assessment. The fate of any gene drive released in a population would be inextricably linked to the population’s ecology. Given the uncertainty often involved in ecological assessment of natural populations, understanding the sensitivity of gene drive spread to important ecological factors is critical. Here we review how different forms of density dependence, spatial heterogeneity, and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
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.
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.
Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination
7941P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov, bioRxiv, 2020.01.27.920421. 2020-02-06 20:32:18.
Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and many-to-many mappings of genotypes to phenotypes to investigate gene flow and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summary Vector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.
Davos 2020 World Economic Forum | When Humankind Overrides Evolution
6813M. Skipper, World Economic Forum, Davos 2020. 2020-01-21 15:32:08.
Advances in synthetic biology and other novel genetic procedures could resurrect extinct species or eliminate dangerous pests. What actions are needed now to ensure the ethical and responsible application of new genetic techniques?
Fitness consequences of a non-recombining sex-ratio drive chromosome can explain its prevalence in the wild
5797Dyer, K. A. and D. W. Hall, Proceedings of the Royal Society B: Biological Sciences, 286:20192529. 2019-12-19 14:27:34.
Understanding the pleiotropic consequences of gene drive systems on host fitness is essential to predict their spread through a host population. Here, we study sex-ratio (SR) X-chromosome drive in the fly Drosophila recens, where SR causes the death of Y-bearing sperm in male carriers. SR males only sire daughters, which all carry SR, thus giving the chromosome a transmission advantage. The prevalence of the SR chromosome appears stable, suggesting pleiotropic costs. It was previously shown that females homozygous for SR are sterile, and here, we test for additional fitness costs of SR. We found that females heterozygous for SR have reduced fecundity and that male SR carriers have reduced fertility in conditions of sperm competition. We then use our fitness estimates to parametrize theoretical models of SR drive and show that the decrease in fecundity and sperm competition performance can account for the observed prevalence of SR in natural populations. In addition, we found that the expected equilibrium frequency of the SR chromosome is particularly sensitive to the degree of multiple mating and performance in sperm competition. Together, our data suggest that the mating system of the organism should be carefully considered during the development of gene drive systems.
Gene drive: progress and prospects
5795Wedell, N., T. A. R. Price and A. K. Lindholm, Proceedings of the Royal Society B: Biological Sciences, 286:20192709. 2019-12-19 14:25:02.
Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading nontarget species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.
Ancient gene drives: an evolutionary paradox
5792Price, T. A. R., R. Verspoor and N. Wedell, Proceedings of the Royal Society B: Biological Sciences, 286:20192267. 2019-12-19 14:21:02.
Selfish genetic elements such as selfish chromosomes increase their transmission rate relative to the rest of the genome and can generate substantial cost to the organisms that carry them. Such segregation distorters are predicted to either reach fixation (potentially causing population extinction) or, more commonly, promote the evolution of genetic suppression to restore transmission to equality. Many populations show rapid spread of segregation distorters, followed by the rapid evolution of suppression. However, not all drivers display such flux, some instead persisting at stable frequencies in natural populations for decades, perhaps hundreds of thousands of years, with no sign of suppression evolving or the driver spreading to fixation. This represents a major evolutionary paradox. How can drivers be maintained in the long term at stable frequencies? And why has suppression not evolved as in many other gene drive systems? Here, we explore potential factors that may explain the persistence of drive systems, focusing on the ancient sex-ratio driver in the fly Drosophila pseudoobscura. We discuss potential solutions to the evolutionary mystery of why suppression does not appear to have evolved in this system, and address how long-term stable frequencies of gene drive can be maintained. Finally, we speculate whether ancient drivers may be functionally and evolutionarily distinct to young drive systems.
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.
Genetically engineering wild mice to combat Lyme disease: An ecological perspective
5631Snow, A. A., BioScience, 69:746-756. 2019-12-17 16:51:55.
Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. For example, CRISPR- based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha’s Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits’ proliferation, pending approvals from relevant constituents. Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats
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.
Winning the tug-of-war between effector gene design and pathogen evolution in vector population replacement strategies
5609Marshall, J. M., R. R. Raban, N. P. Kandul, J. R. Edula, T. M. León and O. S. Akbari, Frontiers in Genetics, 10:1072. 2019-12-17 16:13:33.
While efforts to control malaria with available tools have stagnated, and arbovirus outbreaks persist around the globe, the advent of clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing has provided exciting new opportunities for genetics-based strategies to control these diseases. In one such strategy, called “population replacement”, mosquitoes, and other disease vectors are engineered with effector genes that render them unable to transmit pathogens. These effector genes can be linked to “gene drive” systems that can bias inheritance in their favor, providing novel opportunities to replace disease-susceptible vector populations with disease-refractory ones over the course of several generations. While promising for the control of vector-borne diseases on a wide scale, this sets up an evolutionary tug-of-war between the introduced effector genes and the pathogen. Here, we review the disease-refractory genes designed to date to target Plasmodium falciparum malaria transmitted by Anopheles gambiae, and arboviruses transmitted by Aedes aegypti, including dengue serotypes 2 and 3, chikungunya, and Zika viruses. We discuss resistance concerns for these effector genes, and genetic approaches to prevent parasite and viral escape variants. One general approach is to increase the evolutionary hurdle required for the pathogen to evolve resistance by attacking it at multiple sites in its genome and/or multiple stages of development. Another is to reduce the size of the pathogen population by other means, such as with vector control and antimalarial drugs. We discuss lessons learned from the evolution of resistance to antimalarial and antiviral drugs and implications for the management of resistance after its emergence. Finally, we discuss the target product profile for population replacement strategies for vector-borne disease control. This differs between early phase field trials and wide-scale disease control. In the latter case, the demands on effector gene efficacy are great; however, with new possibilities ushered in by CRISPR-based gene editing, and when combined with surveillance, monitoring, and rapid management of pathogen resistance, the odds are increasingly favoring effector genes in the upcoming evolutionary tug-of-war.
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.
The impact of local population genetic background on the spread of the selfish element Medea-1 in red flour beetles
6379S. A. Cash, M. A. Robert, M. D. Lorenzen and F. Gould, Ecology and Evolution, 12:1-12. 2019-11-10 16:06:41.
Selfish genetic elements have been found in the genomes of many species, yet our understanding of their evolutionary dynamics is only partially understood. A number of distinct selfish Medea elements are naturally present in many populations of the red flour beetle (Tribolium castaneum). Although these Medea elements are predicted by models to increase in frequency within populations because any offspring of a Medea-bearing mother that do not inherit at least one Medea allele will die, experiments demonstrating an increase in a naturally occurring Medea element are lacking. Our survey of the specific Medea element, M-1, in the United States showed that it had a patchy geographic distribution. From the survey, it could not be determined if this distribution was caused by a slow process of M-1 colonization of discrete populations or if some populations lacked M-1 because they had genetic factors conferring resistance to the Medea mechanism. We show that populations with naturally low to intermediate M-1 frequencies likely represent transient states during the process of Medea spread. Furthermore, we find no evidence that genetic factors are excluding M-1 from US populations where the element is not presently found. We also show how a known suppressor of Medea can impair the increase of M-1 in populations and discuss the implications of our findings for pest-management applications of Medea elements.
The distribution and spread of naturally occurring Medea selfish genetic elements in the United States
6383S. A. Cash, M. D. Lorenzen and F. Gould, Ecology and Evolution, 9:14407–14416.. 2019-11-09 16:17:38.
Selfish genetic elements (SGEs) are DNA sequences that are transmitted to viable offspring in greater than Mendelian frequencies. Medea SGEs occur naturally in some populations of red flour beetle (Tribolium castaneum) and are expected to increase in frequency within populations and spread among populations. The large-scale U.S. distributions of Medea-4 (M4) had been mapped based on samples from 1993 to 1995. We sampled beetles in 2011?2014 and show that the distribution of M4 in the United States is dynamic and has shifted southward. By using a genetic marker of Medea-1 (M1), we found five unique geographic clusters with high and low M1 frequencies in a pattern not predicted by microsatellite-based analysis of population structure. Our results indicate the absence of rigid barriers to Medea spread in the United States, so assessment of what factors have limited its current distribution requires further investigation. There is great interest in using synthetic SGEs, including synthetic Medea, to alter or suppress pest populations, but there is concern about unpredicted spread of these SGEs and potential for populations to become resistant to them. The finding of patchy distributions of Medea elements suggests that released synthetic SGEs cannot always be expected to spread uniformly, especially in target species with limited dispersal.
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.
A 2017 horizon scan of emerging issues for global conservation and biological diversity
4067Sutherland, WJB, P.; Broad, S.; Clout, M.; Connor, B.; Cote, I. M.; Dicks, L. V.; Doran, H.; Entwistle, A. C.; Fleishman, E.; Fox, M.; Gaston, K. J.; Gibbons, D. W.; Jiang, Z.; Keim, B.; Lickorish, F. A.; Markillie, P.; Monk, K. A.; Pearce-Higgins, J. W.; Peck, L. S.; Pretty, J.; Spalding, M. D.; Tonneijck, F. H.; Wintle, B. C.; Ockendon, N., Trends in Ecology & Evolution, 32:31-40. 2019-09-09 00:00:00.
We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.
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.
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.
The association between mitochondrial genetic variation and reduced colony fitness in an invasive wasp
13731J. Dobelmann, A. Alexander, J. W. Baty, N. J. Gemmell, M. A. M. Gruber, O. Quinn, T. Wenseleers and P. J. Lester, Molecular Ecology, 28:3324-3338. 2019-06-24 19:25:29.
Despite the mitochondrion's long-recognized role in energy production, mitochondrial DNA (mtDNA) variation commonly found in natural populations was assumed to be effectively neutral. However, variation in mtDNA has now been increasingly linked to phenotypic variation in life history traits and fitness. We examined whether the relative fitness in native and invasive common wasp (Vespula vulgaris) populations in Belgium and New Zealand (NZ), respectively, can be linked to mtDNA variation.
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.
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).
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.
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.
CRISPR gene drive efficiency and resistance rate is highly heritable with no common genetic loci of large effect
3901Champer, JW, Z. X.; Luthra, A.; Reeves, R.; Chung, J.; Liu, C.; Lee, Y. L.; Liu, J. X.; Yang, E.; Messer, P. W.; Clark, A. G., Genetics, 212:333-341. 2019-01-19 00:00:00.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would eventually halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation postfertilization in the early embryo ranged from 7 to 79% among lines and averaged 42 +/- 18%. We performed a genome-wide association study using our results in the DGRP lines, and found that the resistance and conversion rates were not explained by common alleles of large effect, but instead there were several genetic polymorphisms showing weak association. RNA interference knockdown of several genes containing these polymorphisms confirmed their effect, but the small effect sizes imply that their manipulation would likely yield only modest improvements to the efficacy of gene drives.
Variability in the durability of CRISPR-Cas immunity
3899Chabas, HN, A.; Meaden, S.; Westra, E. R.; Tremblay, D. M.; Pradier, L.; Lion, S.; Moineau, S.; Gandon, S., Philosophical Transactions of the Royal Society B-Biological Sciences, 374:1-9. 2019-01-17 00:00:00.
The durability of host resistance is challenged by the ability of pathogens to escape the defence of their hosts. Understanding the variability in the durability of host resistance is of paramount importance for designing more effective control strategies against infectious diseases. Here, we study the durability of various clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas) alleles of the bacteria Streptococcus thermophilus against lytic phages. We found substantial variability in durability among different resistant bacteria. Since the escape of the phage is driven by a mutation in the phage sequence targeted by CRISPR-Cas, we explored the fitness costs associated with these escape mutations. We found that, on average, escape mutations decrease the fitness of the phage. Yet, the magnitude of this fitness cost does not predict the durability of CRISPR-Cas immunity. We contend that this variability in the durability of resistance may be because of variations in phage mutation rate or in the proportion of lethal mutations across the phage genome. These results have important implications on the coevolutionary dynamics between bacteria and phages and for the optimal deployment of resistance strategies against pathogens and pests. Understanding the durability of CRISPR-Cas immunity may also help develop more effective gene-drive strategies based on CRISPR-Cas9 technology. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.
Predicting the spatial dynamics of Wolbachia infections in Aedes aegypti arbovirus vector populations in heterogeneous landscapes
3917Hancock, PAR, S. A.; Koenraadt, C. J. M.; Scott, T. W.; Hoffmann, A. A.; Godfray, H. C. J., Journal of Applied Ecology, 56:1674-1686. 2019-01-15 00:00:00.
A promising strategy for reducing the transmission of dengue and other arboviral human diseases by Aedes aegypti mosquito vector populations involves field introductions of the endosymbiotic bacteria Wolbachia. Wolbachia infections inhibit viral transmission by the mosquito, and can spread between mosquito hosts to reach high frequencies in the vector population. Wolbachia spreads by maternal transmission, and spread dynamics can be variable and highly dependent on natural mosquito population dynamics, population structure and fitness components. We develop a mathematical model of an A. aegypti metapopulation that incorporates empirically validated relationships describing density-dependent mosquito fitness components. We assume that density dependent relationships differ across subpopulations, and construct heterogeneous landscapes for which model-predicted patterns of variation in mosquito abundance and demography approximate those observed in field populations. We then simulate Wolbachia release strategies similar to that used in field trials. We show that our model can produce rates of spatial spread of Wolbachia similar to those observed following field releases. We then investigate how different types of spatio-temporal variation in mosquito habitat, as well as different fitness costs incurred by Wolbachia on the mosquito host, influence predicted spread rates. We find that fitness costs reduce spread rates more strongly when the habitat landscape varies temporally due to stochastic and seasonal processes. Synthesis and applications: Our empirically based modelling approach represents effects of environmental heterogeneity on the spatial spread of Wolbachia. The models can assist in interpreting observed spread patterns following field releases and in designing suitable release strategies for targeting spatially heterogeneous vector populations.
Spatial structure undermines parasite suppression by gene drive cargo
3896Bull, JJR, Christopher H.; Gomulkiewicz, Richard; Krone, Stephen M., PeerJ, 7:e7921. 2019-01-14 00:00:00.
Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.
Making a murderer: The evolutionary framing of hybrid gamete-killers
3949Sweigart, ALB, Yaniv; Fishman, Lila, Trends in Genetics, 35:245-252. 2019-01-07 00:00:00.
Recent molecular investigations of hybrid incompatibilities have revealed fascinating patterns of genetic interactions that have been interpreted as the remnants of a history of selfish evolution. Instead of framing hybrid incompatibilities in light of genetic conflict, we advocate assuming their innocence. Researchers must build a strong theory for each case, supported by population genetic evidence, such that the role of conflict in the evolution of a hybrid incompatibility can be proven beyond reasonable doubt. This will require careful investigation of the evolutionary history of these incompatibilities, a reckoning of how the reproductive biology of study organisms impacts on the likelihood of genetic conflict, and molecular evidence of the rapid selfish spread of these alleles.
Controlling invasive rodents via synthetic gene drive and the role of polyandry
3927Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R., Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-01-05 00:00:00.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three-to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.
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.
Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species
3904Courtier-Orgogozo, VD, Antoine; Gouyon, Pierre-Henri; Boëte, Christophe, bioRxiv, 776609:27. 2019-01-02 00:00:00.
The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct withhyb = probability of hybridization between the target species and a non-target speciestransf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a non-target species (with no hybridization)express = probability that the Cas9 and guide RNA genes are expressedcut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new hostflank = probability that the gene drive cassette inserts at the cut siteimmune = probability that the immune system does not reject Cas9-expressing cellsnonextinct = probability of invasion of the drive within the population We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.CRISPRClustered Regularly Interspaced Short Palindromic RepeatsDRAQUEDrive Risk Assessment Quantitative EstimateHGThorizontal gene transferHTThorizontal transfer of transposable elementTEtransposable element
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii
3962Buchman, AM, John M.; Ostrovski, Dennis; Yang, Ting; Akbari, Omar S., Proceedings of the National Academy of Sciences of the United States of America, 115:4725-4730. 2018-01-20 00:00:00.
Here we describe a fully functional gene drive system constructed in a major worldwide crop pest, Drosophila suzukii. This system is composed of a synthetic Medea drive with a maternal miRNA “toxin” and a zygotic “antidote,” and we demonstrate that it can bias inheritance with 100% efficiency and can persist in a population given high release frequencies. We discuss how such a system may be used to suppress D. suzukii populations or render them harmless to target crops.Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii. We demonstrate that this drive system, based on an engineered maternal “toxin” coupled with a linked embryonic “antidote,” is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.
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.
Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations
3977Hammond, AMK, Kyros; Gribble, Matthew; Karlsson, Xenia; Morianou, Ioanna; Galizi, Roberto; Beaghton, Andrea; Crisanti, Andrea; Nolan, Tony, bioRxiv, 360339:1-16. 2018-01-15 00:00:00.
CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector of malaria, however laboratory demonstrations showed strong unintended fitness costs and high levels of resistant mutations that limited the potential of the first generation of gene drives to spread. We describe three new gene drives designed to restrict spatio-temporal nuclease expression by using novel regulatory sequences. Two of the three new designs dramatically improve fitness and mitigate the creation and selection of resistance. We dissect the relative contributions of germline CRISPR activity versus embryonic CRISPR activity resulting from parental deposition, showing that the improved performance of the new designs is due to tighter germline restriction of the nuclease activity and significantly lower rates of end-joining repair in the embryo. Moreover, we demonstrate in laboratory-contained population experiments that these gene drives show remarkably improved invasion dynamics compared to the first generation drives, resulting in greater than 90% suppression of the reproductive output and a delay in the emergence of target site resistance, even at a loosely constrained target sequence. These results illustrate important considerations for gene drive design and will help expedite the development of gene drives designed to control malaria transmission in Africa.
Genetics and genomics of an unusual selfish sex ratio distortion in an insect
3976Hamilton, PTH, C. N.; Curtis, C. I.; Perlman, S. J., Current Biology, 28:3864-3870. 2018-01-14 00:00:00.
Diverse selfish genetic elements have evolved the ability to manipulate reproduction to increase their transmission, and this can result in highly distorted sex ratios [1]. Indeed, one of the major explanations for why sex determination systems are so dynamic is because they are shaped by ongoing coevolutionary arms races between sex-ratio-distorting elements and the rest of the genome [2]. Here, we use genetic crosses and genome analysis to describe an unusual sex ratio distortion with striking consequences on genome organization in a booklouse species, Liposcelis sp. (Insecta: Psocodea), in which two types of females coexist. Distorter females never produce sons but must mate with males (the sons of nondistorting females) to reproduce [3]. Although they are diploid and express the genes inherited from their fathers in somatic tissues, distorter females only ever transmit genes inherited from their mothers. As a result, distorter females have unusual chimeric genomes, with distorter-restricted chromosomes diverging from their nondistorting counterparts and exhibiting features of a giant non-recombining sex chromosome. The distorter-restricted genome has also acquired a gene from the bacterium Wolbachia, a well-known insect reproductive manipulator; we found that this gene has independently colonized the genomes of two other insect species with unusual reproductive systems, suggesting possible roles in sex ratio distortion in this remarkable genetic system.
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]
Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors
3974Edgington, MPA, Luke S., PLOS Computational Biology, 14:e1006059. 2018-01-12 00:00:00.
Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne diseases are currently being investigated. Among the promising techniques currently being considered are a range of genetic control methods known as gene drive systems. These allow desirable genetic traits (such as a much reduced capacity for vectors to transmit viruses) to be spread through a target population; taking advantage of natural mate seeking behaviour to locate vector sub-populations that can be extremely difficult for humans to locate and reach. Here we use mathematical models (parameterised to consider mosquito populations) to demonstrate the robustness of the engineered underdominance and killer-rescue classes of gene drive to different ecological factors including birth and death rates; the number and quality of breeding sites (i.e. carrying capacity); and the strength of density-dependent competition during the larval development phase. We then go on to explore the range of potential outcomes that may result from the migration of individuals between two neighbouring populations.
Carrying a selfish genetic element predicts increased migration propensity in free-living wild house mice
4012Runge, J-NL, Anna K., Proceedings of the Royal Society B: Biological Sciences, 285:20181333. 2018-01-10 00:00:00.
Life is built on cooperation between genes, which makes it vulnerable to parasitism. Selfish genetic elements that exploit this cooperation can achieve large fitness gains by increasing their transmission relative to the rest of the genome. This leads to counter-adaptations that generate unique selection pressures on the selfish genetic element. This arms race is similar to host–parasite coevolution, as some multi-host parasites alter the host’s behaviour to increase the chance of transmission to the next host. Here, we ask if, similarly to these parasites, a selfish genetic element in house mice, the t haplotype, also manipulates host behaviour, specifically the host’s migration propensity. Variants of the t that manipulate migration propensity could increase in fitness in a meta-population. We show that juvenile mice carrying the t haplotype were more likely to emigrate from and were more often found as migrants within a long-term free-living house mouse population. This result may have applied relevance as the t has been proposed as a basis for artificial gene drive systems for use in population control.
Invasion and migration of spatially self-limiting gene drives: A comparative analysis
3972Dhole, S.; Vella, M. R; Lloyd, A. L.; Gould, F., Evolutionary Applications, 11:794-808. 2018-01-10 00:00:00.
Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self?limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self?limiting gene drive systems: one?locus underdominance, two?locus underdominance and daisy?chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy?chain system is the most efficient, requiring the smallest release, followed by the two?locus underdominance system, and then the one?locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy?chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two?locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one?locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two?locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy?chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.
Unexpected patterns of segregation distortion at a selfish supergene in the fire ant Solenopsis invicta
4010Ross, KGS, DeWayne, BMC Genetics, 19:101. 2018-01-08 00:00:00.
The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this supergene — including suppressed recombination, presence of deleterious mutations, association with a large centromere, and “green-beard” behavior — suggest that it may be a selfish genetic element that engages in transmission ratio distortion (TRD), defined as significant departures in progeny allele frequencies from Mendelian inheritance ratios. We tested this possibility by surveying segregation ratios in embryo progenies of 101 queens of the “polygyne” social form (3512 embryos) using three supergene-linked markers and twelve markers outside the supergene.
Reducing resistance allele formation in CRISPR gene drive
3968Champer, JL, Jingxian; Oh, Suh Yeon; Reeves, Riona; Luthra, Anisha; Oakes, Nathan; Clark, Andrew G.; Messer, Philipp W., Proceedings of the National Academy of Sciences of the United States of America, 115:5522-5527. 2018-01-06 00:00:00.
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the mosquitoes that transmit these diseases. However, recent studies have shown that current drives would likely be unable to spread in insect populations due to the high rate at which resistance will evolve. In this study, we provide an experimental demonstration that guide RNA multiplexing can successfully reduce resistance rates but also find that such an approach would still need to be combined with additional strategies to create drives that are efficient enough for use in wild populations.CRISPR homing gene drives can convert heterozygous cells with one copy of the drive allele into homozygotes, thereby enabling super-Mendelian inheritance. Such a mechanism could be used, for example, to rapidly disseminate a genetic payload in a population, promising effective strategies for the control of vector-borne diseases. However, all CRISPR homing gene drives studied in insects thus far have produced significant quantities of resistance alleles that would limit their spread. In this study, we provide an experimental demonstration that multiplexing of guide RNAs can both significantly increase the drive conversion efficiency and reduce germline resistance rates of a CRISPR homing gene drive in Drosophila melanogaster. We further show that an autosomal drive can achieve drive conversion in the male germline, with no subsequent formation of resistance alleles in embryos through paternal carryover of Cas9. Finally, we find that the nanos promoter significantly lowers somatic Cas9 expression compared with the vasa promoter, suggesting that nanos provides a superior choice in drive strategies where gene disruption in somatic cells could have fitness costs. Comparison of drive parameters among the different constructs developed in this study and a previous study suggests that, while drive conversion and germline resistance rates are similar between different genomic targets, embryo resistance rates can vary significantly. Taken together, our results mark an important step toward developing effective gene drives capable of functioning in natural populations and provide several possible avenues for further control of resistance rates.
Catch me if you can: A spatial model for a brake-driven gene drive reversal
3967Calvez, V,,Debarre, F., Girardin, Leo, arXiv, 1812.06641:1-30. 2018-01-05 00:00:00.
We successfully prove that, whenever the drive fitness is at most 50% of the wild-type one while the brake fitness is close to the wild-type one, co-extinction of the brake and the drive occurs in the long run.
Modelling Allee effects in a transgenic mosquito population during range expansion
4026Walker, MB, Julie C.; Brown, Vicki; Childs, Lauren M., Journal of Biological Dynamics, 13:2-22. 2018-01-04 00:00:00.
Mosquitoes are vectors for many diseases that cause significant mortality and morbidity. As mosquito populations expand their range, they may undergo mate-finding Allee effects such that their ability to successfully reproduce becomes difficult at low population density. With new technology, creating target specific gene modification may be a viable method for mosquito population control. We develop a mathematical model to investigate the effects of releasing transgenic mosquitoes into newly established, low-density mosquito populations. Our model consists of two life stages (aquatic and adults), which are divided into three genetically distinct groups: heterogeneous and homogeneous transgenic that cause female infertility and a homogeneous wild type. We perform analytical and numerical analyses on the equilibria to determine the level of saturation needed to eliminate mosquitoes in a given area. This model demonstrates the potential for a gene drive system to reduce the spread of invading mosquito populations.
B Chromosomes in populations of mammals revisited
4025Vujoševi?, MR, Marija; Blagojevi?, Jelena, Genes, 9:487. 2018-01-03 00:00:00.
The study of B chromosomes (Bs) started more than a century ago, while their presence in mammals dates since 1965. As the past two decades have seen huge progress in application of molecular techniques, we decided to throw a glance on new data on Bs in mammals and to review them. We listed 85 mammals with Bs that make 1.94% of karyotypically studied species. Contrary to general view, a typical B chromosome in mammals appears both as sub- or metacentric that is the same size as small chromosomes of standard complement. Both karyotypically stable and unstable species possess Bs. The presence of Bs in certain species influences the cell division, the degree of recombination, the development, a number of quantitative characteristics, the host-parasite interactions and their behaviour. There is at least some data on molecular structure of Bs recorded in nearly a quarter of species. Nevertheless, a more detailed molecular composition of Bs presently known for six mammalian species, confirms the presence of protein coding genes, and the transcriptional activity for some of them. Therefore, the idea that Bs are inert is outdated, but the role of Bs is yet to be determined. The maintenance of Bs is obviously not the same for all species, so the current models must be adapted while bearing in mind that Bs are not inactive as it was once thought.
Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs
4005Oberhofer, GI, Tobin; Hay, Bruce A., Proceedings of the National Academy of Sciences of the United States of America, 115:e9343. 2018-01-03 00:00:00.
Homing endonuclease gene (HEG)-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage but that retain wild-type gene function. We show that resistance allele creation can be prevented through the use of guide RNAs designed to cleave a gene at four target sites. However, homing rates were modest, and the HEGs were unstable during homing. In addition, use of a promoter active in the female germline resulted in levels of HEG carryover that compromised the viability or fertility of HEG-bearing heterozygotes, thereby preventing drive. We propose strategies that can help to overcome these problems in next-generation HEG systems.A gene drive method of particular interest for population suppression utilizes homing endonuclease genes (HEGs), wherein a site-specific, nuclease-encoding cassette is copied, in the germline, into a target gene whose loss of function results in loss of viability or fertility in homozygous, but not heterozygous, progeny. Earlier work in Drosophila and mosquitoes utilized HEGs consisting of Cas9 and a single guide RNA (gRNA) that together target a specific gene for cleavage. Homing was observed, but resistant alleles immune to cleavage, while retaining wild-type gene function, were also created through nonhomologous end joining. Such alleles prevent drive and population suppression. Targeting a gene for cleavage at multiple positions has been suggested as a strategy to prevent the appearance of resistant alleles. To test this hypothesis, we generated two suppression HEGs in Drosophila melanogaster targeting genes required for embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and gRNAs designed to cleave each gene at four positions. Rates of target locus cleavage were very high, and multiplexing of gRNAs prevented resistant allele formation. However, germline homing rates were modest, and the HEG cassette was unstable during homing events, resulting in frequent partial copying of HEGs that lacked gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments, the HEGs failed to spread due to the high fitness load induced in offspring as a result of maternal carryover of Cas9/gRNA complex activity. Alternative design principles are proposed that may mitigate these problems in future gene drive engineering.
Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management
3985Carrami, Eli M., ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A., Proceedings of the National Academy of Sciences of the United States of America, 115:6189-6194. 2018-01-03 00:00:00.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles can be produced readily and inherently in a suppression gene-drive system. The rate at which such alleles emerge will determine the maximum size of the population that could be targeted for collapse and elimination. Here, we provide a potential target site and the modeling framework for implementation and optimization of a suppression gene-drive strategy to control Mediterranean fruit fly populations.The use of a site-specific homing-based gene drive for insect pest control has long been discussed, but the easy design of such systems has become possible only with the recent establishment of CRISPR/Cas9 technology. In this respect, novel targets for insect pest management are provided by new discoveries regarding sex determination. Here, we present a model for a suppression gene drive designed to cause an all-male population collapse in an agricultural pest insect. To evaluate the molecular details of such a sex conversion-based suppression gene drive experimentally, we implemented this strategy in Drosophila melanogaster to serve as a safe model organism. We generated a Cas9-based homing gene-drive element targeting the transformer gene and showed its high efficiency for sex conversion from females to males. However, nonhomologous end joining increased the rate of mutagenesis at the target site, which resulted in the emergence of drive-resistant alleles and therefore curbed the gene drive. This confirms previous studies that simple homing CRISPR/Cas9 gene-drive designs will be ineffective. Nevertheless, by performing population dynamics simulations using the parameters we obtained in D. melanogaster and by adjusting the model for the agricultural pest Ceratitis capitata, we were able to identify adequate modifications that could be successfully applied for the management of wild Mediterranean fruit fly populations using our proposed sex conversion-based suppression gene-drive strategy.
Self-limiting population genetic control with sex-linked genome editors
3965Burt, AD, Anne, Proceedings of the Royal Society B: Biological Sciences, 285:20180776. 2018-01-03 00:00:00.
In male heterogametic species the Y chromosome is transmitted solely from fathers to sons, and is selected for based only on its impacts on male fitness. This fact can be exploited to develop efficient pest control strategies that use Y-linked editors to disrupt the fitness of female descendants. With simple population genetic and dynamic models we show that Y-linked editors can be substantially more efficient than other self-limiting strategies and, while not as efficient as gene drive approaches, are expected to have less impact on non-target populations with which there is some gene flow. Efficiency can be further augmented by simultaneously releasing an autosomal X-shredder construct, in either the same or different males. Y-linked editors may be an attractive option to consider when efficient control of a species is desired in some locales but not others.
Transmission and drive involving parasitic B chromosomes
3984Jones, RN, Genes, 9:e388. 2018-01-02 00:00:00.
B chromosomes (Bs) are enigmatic additional elements in the genomes of thousands of species of plants, animals, and fungi. How do these non-essential, harmful, and parasitic chromosomes maintain their presence in their hosts, making demands on all the essential functions of their host genomes? The answer seems to be that they have mechanisms of drive which enable them to enhance their transmission rates by various processes of non-mendelian inheritance. It is also becoming increasingly clear that the host genomes are developing their own mechanisms to resist the impact of the harmful effects of the Bs.
How driving endonuclease genes can be used to combat pests and disease vectors
4043Godfray, HCJN, A.; Burt, A., BMC Biology, 15:81. 2017-01-21 00:00:00.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the homologue as a template the DEG heterozygote is converted to a homozygote. Some DEGs occur naturally while several classes of endonucleases can be engineered to spread in this way, with CRISPR-Cas9 based systems being particularly flexible. There is great interest in using driving endonuclease genes to impose a genetic load on insects that vector diseases or are economic pests to reduce their population density, or to introduce a beneficial gene such as one that might interrupt disease transmission. This paper reviews both the population genetics and population dynamics of DEGs. It summarises the theory that guides the design of DEG constructs intended to perform different functions. It also reviews the studies that have explored the likelihood of resistance to DEG phenotypes arising, and how this risk may be reduced. The review is intended for a general audience and mathematical details are kept to a minimum.
Is it time for synthetic biodiversity conservation?
4062Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K., Trends in Ecology & Evolution, 32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.
Evolutionary dynamics of CRISPR gene drives
4059Noble, CO, Jason; Esvelt, Kevin M.; Church, George M.; Nowak, Martin A., Science Advances, 3:e1601964. 2017-01-17 00:00:00.
The alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) gene drives—selfish genetic elements that can spread through populations even if they confer no advantage to their host organism—are rapidly emerging as the most promising approach. However, before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design that selects against resistant alleles could greatly improve evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights that inform the engineering of practical gene drive systems.%U
CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations
4038Drury, DWD, A. L.; Siniard, D. J.; Zentner, G. E.; Wade, M. J., Science Advances, 3:e1601910. 2017-01-16 00:00:00.
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.
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.
Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations
4034Champer, JR, Riona; Oh, Suh Yeon; Liu, Chen; Liu, Jingxian; Clark, Andrew G.; Messer, Philipp W., PLOS Genetics, 13:e1006796. 2017-01-12 00:00:00.
Author summary Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. For example, a functioning gene drive system could rapidly spread a genetically modified allele designed to reduce pathogen transmission throughout a vector population. The recently developed CRISPR/Cas9-based gene drive mechanism works by converting wild type alleles to drive alleles in heterozygotes via cleavage and homology-directed repair. However, resistance alleles that are unable to be converted to drive alleles can also be generated during this process, which may pose a major obstacle to the practical use of such gene drives. In our study, we developed two CRISPR/Cas9 gene drive constructs using different promoters and target sites in the model organism Drosophila melanogaster. We observed that these constructs produced resistance alleles at high rates both in the germline and post-fertilization in the embryo. Additionally, conversion efficiency and resistance allele formation rates varied substantially among genetically diverse fly lines. Overall, we conclude that new gene drive approaches will be necessary to reduce the formation of resistance alleles, particularly in genetically diverse natural populations.
X chromosome drive in a widespread Palearctic woodland fly, Drosophila testacea
4052Keais, GLH, M. A.; Gowen, B. E.; Perlman, S. J., Journal of Evolutionary Biology, 30:1185-1194. 2017-01-10 00:00:00.
Selfish genes that bias their own transmission during meiosis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes have important evolutionary and ecological consequences, and can be found in a broad range of taxa including plants, mammals and insects. Here, we report a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. We show that males carrying the driving X (SR males) sire 80-100% female offspring and possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. We find that the majority of sons produced by SR males are sterile and appear to lack a Y chromosome, suggesting that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. By screening wild-caught flies using progeny sex ratios and a diagnostic marker, we demonstrate that the driving X is present in wild populations at a frequency of similar to 10% and that suppressors of drive are segregating in the same population. The testacea species group appears to be a hot spot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves.
Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing
4031Beaghton, AH, Andrew; Nolan, Tony; Crisanti, Andrea; Godfray, H. Charles J.; Burt, Austin, Genetics, 205:1587-1596. 2017-01-09 00:00:00.
There is a need for new interventions against the ongoing burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing reaction as a form of gene drive to spread those genes through target populations. If the effector gene reduces the fitness of the mosquito and does not contribute to the drive, then loss-of-function mutations in the effector will eventually replace functional copies, but protection may nonetheless persist sufficiently long to provide a public health benefit. Here, we present a quantitative model allowing one to predict the duration of protection as a function of the probabilities of different molecular processes during the homing reaction, various fitness effects, and the efficacy of the effector in blocking transmission. Factors that increase the duration of protection include reducing the frequency of pre-existing resistant alleles, the probability of nonrecombinational DNA repair, the probability of homing-associated loss of the effector, the fitness costs of the nuclease and effector, and the completeness of parasite blocking. For target species that extend over an area much larger than the typical dispersal distance, the duration of protection is expected to be highest at the release site, and decrease away from there, eventually falling to zero, as effector-less drive constructs replace effector-containing ones. We also model an alternative strategy of using the nuclease to target an essential gene, and then linking the effector to a sequence that restores the essential function and is resistant to the nuclease. Depending upon parameter values, this approach can prolong the duration of protection. Our models highlight the key design criteria needed to achieve a desired level of public health benefit.%U http://www.genetics.org/content/genetics/205/4/1587.full.pdf
Evolution of Resistance Against CRISPR/Cas9 Gene Drive
4070Unckless, RLC, A. G.; Messer, P. W., Genetics, 205:827-841. 2017-01-08 00:00:00.
CRISPR/Cas9 gene drive (CGD) promises to be a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains unclear to what extent potential resistance mechanisms will affect the dynamics of this process in large natural populations. Here we develop a comprehensive population genetic framework for modeling CGD dynamics, which incorporates potential resistance mechanisms as well as random genetic drift. Using this framework, we calculate the probability that resistance against CGD evolves from standing genetic variation, de novo mutation of wild-type alleles, or cleavage repair by nonhomologous end joining (NHEJ)-a likely by-product of CGD itself. We show that resistance to standard CGD approaches should evolve almost inevitably in most natural populations, unless repair of CGD-induced cleavage via NHEJ can be effectively suppressed, or resistance costs are on par with those of the driver. The key factor determining the probability that resistance evolves is the overall rate at which resistance alleles arise at the population level by mutation or NHEJ. By contrast, the conversion efficiency of the driver, its fitness cost, and its introduction frequency have only minor impact. Our results shed light on strategies that could facilitate the engineering of drivers with lower resistance potential, and motivate the possibility to embrace resistance as a possible mechanism for controlling a CGD approach. This study highlights the need for careful modeling of the population dynamics of CGD prior to the actual release of a driver construct into the wild.
Vector control with driving Y chromosomes: modelling the evolution of resistance
4030Beaghton, AB, P. J.; Burt, A., Malaria Journal, 16:286. 2017-01-08 00:00:00.
: The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio. Methods: A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles. Results: The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles. Conclusions: As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.
A large gene family in fission yeast encodes spore killers that subvert Mendel’s law
4049Hu, WJ, Z. D.; Suo, F.; Zheng, J. X.; He, W. Z.; Du, L. L., eLife, 6:e28567. 2017-01-07 00:00:00.
Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve.
The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
4046Hammond, AMK, Kyros; Bruttini, Marco; North, Ace; Galizi, Roberto; Karlsson, Xenia; Kranjc, Nace; Carpi, Francesco M.; D’Aurizio, Romina; Crisanti, Andrea; Nolan, Tony, PLOS Genetics, 13:e1007039. 2017-01-04 00:00:00.
Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting enzyme CRISPR have been shown recently to be highly efficient at copying themselves from one chromosome to the other during the process of gamete formation in mosquitoes, resulting in transmission to 99% of offspring instead of the 50% expected for a single gene copy. One proposed use for CRISPR-based gene drives is in the control of mosquitoes by designing the gene drive to target mosquito genes involved in fertility, thereby reducing their overall reproductive output and leading to population suppression. Like any intervention designed to suppress a population these gene drives are expected to select for mutations in the mosquito that are resistant to the drive and restore fertility to mosquitoes. We have analyzed the origin and selection of resistant alleles in caged populations of mosquitoes initiated with a gene drive construct targeting a female fertility gene. We find the selected alleles are in-frame insertions and deletions that are resistant to cleavage and restore female fertility. Our findings allow us to improve predictions on gene drive behaviour and to make concrete recommendations on how to improve future gene drive designs by decreasing the likelihood that they generate resistance.
CRISPR/Cas9 gene drive: Growing pains for a new technology
4064Reed, FA, Genetics, 205:1037-1039. 2017-01-02 00:00:00.
In this commentary, Floyd Reed discusses Unckless et al. (2017),; “Evolution of resistance against CRISPR/Cas9 gene drive,”; which was published in the February issue of GENETICS.
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.
Occasional recombination of a selfish X-chromosome may permit its persistence at high frequencies in the wild
4096Pieper, KED, K. A., Journal of Evolutionary Biology, 29:2229-2241. 2016-01-14 00:00:00.
The sex-ratio X-chromosome (SR) is a selfish chromosome that promotes its own transmission to the next generation by destroying Y-bearing sperm in the testes of carrier males. In some natural populations of the fly Drosophila neotestacea, up to 30% of the X-chromosomes are SR chromosomes. To investigate the molecular evolutionary history and consequences of SR, we sequenced SR and standard (ST) males at 11 X-linked loci that span the ST X-chromosome and at seven arbitrarily chosen autosomal loci from a sample of D. neotestacea males from throughout the species range. We found that the evolutionary relationship between ST and SR varies among individual markers, but genetic differentiation between SR and ST is chromosome-wide and likely due to large chromosomal inversions that suppress recombination. However, SR does not consist of a single multilocus haplotype: we find evidence for gene flow between ST and SR at every locus assayed. Furthermore, we do not find long-distance linkage disequilibrium within SR chromosomes, suggesting that recombination occurs in females homozygous for SR. Finally, polymorphism on SR is reduced compared to that on ST, and loci displaying signatures of selection on ST do not show similar patterns on SR. Thus, even if selection is less effective on SR, our results suggest that gene flow with ST and recombination between SR chromosomes may prevent the accumulation of deleterious mutations and allow its long-term persistence at relatively high frequencies.
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.
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.
The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster
13733D. K. Dowling, D. M. Tompkins and N. J. Gemmell, Evolutionary Applications, 8:8710880. 2015-07-15 19:28:56.
The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. However, applicability of the TFT relies on mitochondrial mutations whose male-sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT-mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes
Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment
4122Manser, AK, B.; Lindholm, A. K., Journal of Evolutionary Biology, 28:54-64. 2015-01-20 00:00:00.
The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that - for the first time - allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes.
Coevolutionary dynamics of polyandry and sex-linked meiotic drive
4118Holman, LP, T. A. R.; Wedell, N.; Kokko, H., Evolution, 69:709-720. 2015-01-16 00:00:00.
Segregation distorters located on sex chromosomes are predicted to sweep to fixation and cause extinction via a shortage of one sex, but in nature they are often found at low, stable frequencies. One potential resolution to this longstanding puzzle involves female multiple mating (polyandry). Because many meiotic drivers severely reduce the sperm competitive ability of their male carriers, females are predicted to evolve more frequent polyandry and thereby promote sperm competition when a meiotic driver invades. Consequently, the driving chromosome's relative fitness should decline, halting or reversing its spread. We used formal modeling to show that this initially appealing hypothesis cannot resolve the puzzle alone: other selective pressures (e.g., low fitness of drive homozygotes) are required to establish a stable meiotic drive polymorphism. However, polyandry and meiotic drive can strongly affect one another's frequency, and polyandrous populations may be resistant to the invasion of rare drive mutants.
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.
On the origin of sex chromosomes from meiotic drive
4127Ubeda, FP, M. M.; Wild, G., Proceedings of the Royal Society B-Biological Sciences, 282:20141932. 2015-01-05 00:00:00.
Most animals and many plants make use of specialized chromosomes (sex chromosomes) to determine an individual's sex. Best known are the XY and ZW sex-determination systems. Despite having evolved numerous times, sex chromosomes present something of an evolutionary puzzle. At their origin, alleles that dictate development as one sex or the other (primitive sex chromosomes) face a selective penalty, as they will be found more often in the more abundant sex. How is it possible that primitive sex chromosomes overcome this disadvantage? Any theory for the origin of sex chromosomes must identify the benefit that outweighs this cost and enables a sex-determining mutation to establish in the population. Here we show that a new sex-determining allele succeeds when linked to a sex-specific meiotic driver. The new sex-determining allele benefits from confining the driving allele to the sex in which it gains the benefit of drive. Our model requires few special assumptions and is sufficiently general to apply to the evolution of sex chromosomes in outbreeding cosexual or dioecious species. We highlight predictions of the model that can discriminate between this and previous theories of sex-chromosome origins.
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.
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.
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.
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.
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.
Evidence for meiotic drive as an explanation for karyotype changes in fishes
4148Molina, WFM, P. A.; Bertollo, L. A. C.; Bidau, C. J., Marine Genomics, 15:29-34. 2014-01-06 00:00:00.
The process of preferential chromosome segregation during meiosis has been suggested to be responsible for the predominance of certain chromosome types in the karyotypes of mammals, birds and insects. We developed an extensive analysis of the fixation of mono- or bibrachial chromosomes in the karyotypes of the large Actinopterygii fish group, a key link in the evolution of terrestrial vertebrates, in order to investigate the generality of meiotic drive in determining karyotypic macrotrends. Unlike mammals, fishes have markedly undergone several types of preferential chromosomal rearrangements throughout evolution. Data from the analyzed orders indicate a prevalence of karyotypes with few (<33%) or many (>66%) acrocentric chromosomes and a low number of karyotypes with balanced numbers of mono- and bi-brachial elements. Parallel trends towards a higher number of karyotypes with prevalence of monobrachial chromosomes occurred in phylogenetically close orders (e.g. Perciformes and Tetraodontiformes, and in the order Mugiliformes) and in clades with prevalence of bibrachial elements (e.g. Characiformes, Gymnotiformes, Siluriformes, and Cypriniformes). Some orders where fewer species were available for study, such as Atheriniformes and Anguilliformes, showed karyotype assemblages where both trends were present. Our results strongly suggest a primary role of meiotic drive in karyotypic evolution as indicated by the accumulation of monobrachial chromosomes in Perciformes and Cypriniformes, or bibrachial chromosomes in Siluriformes and Characiformes. Further examinations of the interaction between life history traits, environmental characteristics, and the fixation of chromosomal rearrangements would be exceedingly valuable.
Preferential accumulation of sex and Bs chromosomes in biarmed karyotypes by meiotic drive and rates of chromosomal changes in fishes
4147Molina, WFM, P. A.; Bertollo, L. A. C.; Bidau, C. J., Anais Da Academia Brasileira De Ciencias, 86:1801-1812. 2014-01-05 00:00:00.
Mechanisms of accumulation based on typical centromeric drive or of chromosomes carrying pericentric inversions are adjusted to the general karyotype differentiation in the principal Actinopterygii orders. Here, we show that meiotic drive in fish is also supported by preferential establishment of sex chromosome systems and B chromosomes in orders with predominantly bi-brachial chromosomes. The mosaic of trends acting at an infra-familiar level in fish could be explained as the interaction of the directional process of meiotic drive as background, modulated on a smaller scale by adaptive factors or specific karyotypic properties of each group, as proposed for the orthoselection model.
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).
Evolution and biology of supernumerary B chromosomes
4144Houben, AB-M, A. M.; Klemme, S.; Timmis, J. N., Cellular and Molecular Life Sciences, 71:467-478. 2014-01-02 00:00:00.
B chromosomes (Bs) are dispensable components of the genome exhibiting non-Mendelian inheritance and have been widely reported on over several thousand eukaryotes, but still remain an evolutionary mystery ever since their first discovery over a century ago [1]. Recent advances in genome analysis have significantly improved our knowledge on the origin and composition of Bs in the last few years. In contrast to the prevalent view that Bs do not harbor genes, recent analysis revealed that Bs of sequenced species are rich in gene-derived sequences. We summarize the latest findings on supernumerary chromosomes with a special focus on the origin, DNA composition, and the non-Mendelian accumulation mechanism of Bs.
The dynamic relationship between polyandry and selfish genetic elements
4181Wedell, N, Philosophical Transactions of the Royal Society B-Biological Sciences, 368:10. 2013-01-19 00:00:00.
Selfish genetic elements (SGEs) are ubiquitous in eukaryotes and bacteria, and make up a large part of the genome. They frequently target sperm to increase their transmission success, but these manipulations are often associated with reduced male fertility. Low fertility of SGE-carrying males is suggested to promote polyandry as a female strategy to bias paternity against male carriers. Support for this hypothesis is found in several taxa, where SGE-carrying males have reduced sperm competitive ability. In contrast, when SGEs give rise to reproductive incompatibilities between SGE-carrying males and females, polyandry is not necessarily favoured, irrespective of the detrimental impact on male fertility. This is due to the frequency-dependent nature of these incompatibilities, because they will decrease in the population as the frequency of SGEs increases. However, reduced fertility of SGE-carrying males can prevent the successful population invasion of SGEs. In addition, SGEs can directly influence male and female mating behaviour, mating rates and reproductive traits (e. g. female reproductive tract length and male sperm). This reveals a potent and dynamic interaction between SGEs and polyandry highlighting the potential to generate sexual selection and conflict, but also indicates that polyandry can promote harmony within the genome by undermining the spread of SGEs.
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.
Transmission rate variation among three B chromosome variants in the fish Prochilodus lineatus (Characiformes, Prochilodontidae)
4178Penitente, MV, T. A.; Senhorini, J. A.; Bortolozzi, J.; Foresti, F.; Porto-Foresti, F., Anais Da Academia Brasileira De Ciencias, 85:1371-1377. 2013-01-16 00:00:00.
Cytogenetic studies were developed in Prochilodus lineatus (Valenciennes 1836), describing an interesting system of small supernumerary chromosomes. The purpose of this work is to study the frequency and morphology of B chromosomes in individuals from the parental line and the inheritance patterns of these elements in individuals obtained from controlled crosses in the species P. lineatus. The transmission rate of B chromosomes, revealed a k(B)=0.388 for the acrocentric type, a kB=0.507 for the metacentric type and a k(B)=0.526 for the submetacentric type. The obtained results raise hypothesis that B-acrocentric chromosomes are involved in an extinction process in this species, while the metacentric and submetacentric supernumerary elements comprises a neutral mechanism and follows a Mendelian transmission rate.
Spread of a new parasitic B chromosome variant is facilitated by high gene flow
4176Manrique-Poyato, MIL-L, M. D.; Cabrero, J.; Perfectti, F.; Camacho, J. P. M., PLOS One, 8:e83712. 2013-01-14 00:00:00.
The B-24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B-24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise N(e)m estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B-24 diffusion both eastward and westward, with minor role for B-24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.
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.
Natural variation of the Y chromosome suppresses sex ratio distortion and modulates testis-specific gene expression in Drosophila simulans
4167Branco, ATT, Y.; Hartl, D. L.; Lemos, B., Heredity, 111:8-15. 2013-01-05 00:00:00.
X-linked sex-ratio distorters that disrupt spermatogenesis can cause a deficiency in functional Y-bearing sperm and a female-biased sex ratio. Y-linked modifiers that restore a normal sex ratio might be abundant and favored when a X-linked distorter is present. Here we investigated natural variation of Y-linked suppressors of sex-ratio in the Winters systems and the ability of these chromosomes to modulate gene expression in Drosophila simulans. Seventy-eight Y chromosomes of worldwide origin were assayed for their resistance to the X-linked sex-ratio distorter gene Dox. Y chromosome diversity caused males to sire similar to 63% to similar to 98% female progeny. Genome-wide gene expression analysis revealed hundreds of genes differentially expressed between isogenic males with sensitive (high sex ratio) and resistant (low sex ratio) Y chromosomes from the same population. Although the expression of about 75% of all testis-specific genes remained unchanged across Y chromosomes, a subset of post-meiotic genes was upregulated by resistant Y chromosomes. Conversely, a set of accessory gland-specific genes and mitochondrial genes were downregulated in males with resistant Y chromosomes. The D. simulans Y chromosome also modulated gene expression in XXY females in which the Y-linked protein-coding genes are not transcribed. The data suggest that the Y chromosome might exert its regulatory functions through epigenetic mechanisms that do not require the expression of protein-coding genes. The gene network that modulates sex ratio distortion by the Y chromosome is poorly understood, other than that it might include interactions with mitochondria and enriched for genes expressed in post-meiotic stages of spermatogenesis.
Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans
4166Bastide, HG, P. R.; Ogereau, D.; Cazemajor, M.; Montchamp-Moreau, C., Molecular Ecology, 22:5352-5367. 2013-01-04 00:00:00.
By distorting Mendelian transmission to their own advantage, X-linked meiotic drive elements can rapidly spread in natural populations, generating a sex-ratio bias. One expected consequence is the triggering of a co-evolutionary arms race between the sex chromosome that carries the distorter and suppressors counteracting its effect. Such an arms race has been theoretically and experimentally established and can have many evolutionary consequences. However, its dynamics in contemporary populations is still poorly documented. Here, we investigate the fate of the young X-linked Paris driver in Drosophila simulans from sub-Saharan Africa to the Middle East. We provide the first example of the early dynamics of distorters and suppressors: we find consistent evidence that the driving chromosomes have been rising in the Middle East during the last decade. In addition, identical haplotypes are at high frequencies around the two co-evolving drive loci in remote populations, implying that the driving X chromosomes share a recent common ancestor and suggesting that East Africa could be the cradle of the Paris driver. The segmental duplication associated with drive presents an unusual structure in West Africa, which could reflect a secondary state of the driver. Together with our previous demonstration of driver decline in the Indian Ocean where suppression is complete, these data provide a unique picture of the complex dynamics of a co-evolutionary arms race currently taking place in natural populations of D.simulans.
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.
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.
Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms
4189Koide, YS, Y.; Ikenaga, M.; Sawamura, N.; Matsubara, K.; Onishi, K.; Kanazawa, A.; Sano, Y., Heredity, 108:242-247. 2012-01-07 00:00:00.
Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (SITRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S-6 locus-mediated SITRD, in which the S-6 allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S-6(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S-6 locus-mediated SITRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S-6 locus-mediated SITRD, raising the possibility that SITRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations. Heredity (2012) 108, 242-247; doi:10.1038/hdy.2011.64; published online 27 July 2011
B chromosomes in plants
4188Jones, N, Plant Biosystems, 146:727-737. 2012-01-06 00:00:00.
B chromosomes (Bs) can be described as "selfish chromosomes", a term that has been used for the repetitive DNA which comprises the bulk of the genome in large genome species, except that Bs have a life of their own as independent chromosomes. They can accumulate in number by various processes of mitotic or meiotic drive, especially in the gametophyte phase of the life cycle of flowering plants. This parasitic property of drive ensures their survival and spread in natural populations, even against a gradient of harmful effects on the host plant phenotype. B chromosomes are inhabitants of the nucleus and they are subject to control by "genes" in the A chromosome (As) complement. This interaction with the As, together with the balance between drive and harmful effects makes a dynamic system in the life of a Bs. In this review, we concentrate mainly on recent developments in the Bs of rye and maize, two of the species currently receiving most attention. We focus on their population dynamics and on the molecular basis of their structural organisation and mechanisms of drive, as well as on their mode of origin and potential applications in plant biotechnology.
Local selection underlies the geographic distribution of sex-ratio drive in Drosophila neotestacea
4186Dyer, KA, Evolution, 66:973-984. 2012-01-04 00:00:00.
Selfish genetic elements promote their own transmission to the next generation, often at a cost to the host individual. A sex-ratio (SR) driving X chromosome prevents the maturation of Y-bearing sperm, and as a result is transmitted to 100% of the offspring, all of which are female. Because the spread of a SR chromosome can result in a female-biased population sex ratio, the ecological and evolutionary consequences of harboring this selfish element can be severe. In this study, we show that the prevalence of SR drive in Drosophila neotestacea varies between 0% and 30% among populations, and is common in the south whereas rare in the north. The prevalence of SR is not associated with the presence of suppressors of drive, geographic distance, or genetic distance based on autosomal microsatellite loci. Instead, our results indicate that ecological selection on SR drive varies among populations, as the prevalence of SR is highly correlated with climatic factors, with the severity of winter the best determinant of SR frequency. Thus, ecological and demographic factors may have significant consequences for the short and long term evolutionary dynamics of selfish elements and the manner with which they coevolve with the rest of the genome.
Reduced polymorphism associated with X chromosome meiotic drive in the stalk-eyed fly Teleopsis dalmanni
4202Christianson, SJB, C. L.; Wilkinson, G. S., PLOS One, 6:e27254. 2011-01-20 00:00:00.
Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies.
B Chromosomes and Sex in Animals
4200Camacho, JPMS, M.; Cabrero, J., Sexual Development, 5:155-166. 2011-01-18 00:00:00.
Supernumerary (B) chromosomes are dispensable elements found in many eukaryote genomes in addition to standard (A) chromosomes. In many respects, B chromosomes resemble sex chromosomes, so that a common ancestry for them has frequently been suggested. For instance, B chromosomes in grasshoppers, and other insects, show a pycnotic cycle of condensation-decondensation during meiosis remarkably similar to that of the X chromosome. In some cases, B chromosome size is even very similar to that of the X chromosome. These resemblances have led to suggest the X as the B ancestor in many cases. In addition, sex chromosome origin from B chromosomes has also been suggested. In this article, we review the existing evidence for both evolutionary pathways, as well as sex differences for B frequency at adult and embryo progeny levels, B chromosome effects or B chromosome transmission. In addition, we review cases found in the literature showing sex-ratio distortion associated with B chromosome presence, the most extreme case being the paternal sex ratio (PSR) chromosomes in some Hymenoptera. We finally analyse the possibility of B chromosome regularisation within the host genome and, as a consequence of it, whether B chromosomes can become regular members of the host genome. Copyright (C) 2011 S. Karger AG, Basel
Rapid rise and fall of selfish sex-ratio X Chromosomes in Drosophila simulans: Spatiotemporal analysis of phenotypic and molecular data
4199Bastide, HC, M.; Ogereau, D.; Derome, N.; Hospital, F.; Montchamp-Moreau, C., Molecular Biology and Evolution, 28:2461-2470. 2011-01-17 00:00:00.
Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.
Selfish genetic elements, genetic conflict, and evolutionary innovation
4210Werren, JH, Proceedings of the National Academy of Sciences of the United States of America, 108:10863-10870. 2011-01-08 00:00:00.
Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible "evolutionary functions" of SGEs.
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
Games in tetrads: Segregation, recombination, and meiotic drive
4215Haig, D, American Naturalist, 176:404-413. 2010-01-13 00:00:00.
The two alleles at a heterozygous locus segregate during meiosis, sometimes at meiosis I and sometimes at meiosis II. The timing of segregation is determined by the pattern of crossing-over between a locus and its attached centromeres. Genes near centromeres can exploit this process by driving against spores from which the genes separated at meiosis I. Other genes, located distal to centromeres, can benefit from driving against spores from which they separated at meiosis II. Asymmetric female meiosis is particularly susceptible to such forms of drive. Selection on modifiers of recombination favors changes in the location of chiasmata that increase the proportion of tetrads of high average fitness by changing the timing of segregation. Such changes increase the frequency of driving alleles. This source of selection on recombination does not depend on effects on linkage disequilibrium. Recombinational responses to meiotic drive may contribute to sex differences in overall recombination and sex differences in the localization of chiasmata.
Evolution of the Schlafen genes, a gene family associated with embryonic lethality, meiotic drive, immune processes and orthopoxvirus virulence
4221Bustos, ON, S.; Ayers, G.; Casola, C.; Perez-Lamigueiro, M. A.; Chippindale, P. T.; Pritham, E. J.; de la Casa-Esperon, E., Gene, 447:11-Jan. 2009-01-19 00:00:00.
Genes of the Schlafen family, first discovered in mouse, are expressed in hematopoietic cells and are involved in immune processes. Previous results showed that they are candidate genes for two major phenomena: meiotic drive and embryonic lethality (DDK syndrome). However, these genes remain poorly understood, mostly due to the limitations imposed by their similarity, close location and the potential functional redundancy of the gene family members. Here we use genomic and phylogenetic studies to investigate the evolution and role of this family of genes. Our results show that the Schlafen family is widely distributed in mammals, where we recognize four major clades that experienced lineage-specific expansions or contractions in various orders, including primates and rodents. In addition, we identified members of the Schlafen family in Chondrichthyes and Amphibia, indicating an ancient origin of these genes. We find evidence that positive selection has acted on many Schlafen genes. Moreover, our analyses indicate that a member of the Schlafen family was horizontally transferred from murine rodents to orthopoxviruses, where it is hypothesized to play a role in allowing the virus to survive host immune defense mechanisms. The functional relevance of the viral Schlafen sequences is further underscored by our finding that they are evolving under purifying selection. This is of particular importance, since orthopoxviruses infect mammals and include variola, the causative agent of smallpox, and monkeypox, an emerging virus of great concern for human health. (C) 2009 Elsevier B.V. All rights reserved.
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.
Sex ratio distorter reduces sperm competitive ability in an insect
4243Price, TARB, A. J.; Avent, T. D.; Snook, R. R.; Hurst, G. D. D.; Wedell, N., Evolution, 62:1644-1652. 2008-01-21 00:00:00.
Selfish genetic elements (SGEs) are ubiquitous in animals and often associated with low male fertility due to reduced sperm number in male carriers. In the fruit fly Drosophila pseudoobscura, the meiotic driving X chromosome "sex ratio" kills Y-bearing sperm in carrier males (SR males), resulting in female only broods. We competed SR males against the ejaculates of noncarrying standard males (ST males), and quantified the number of sperm transferred by SR and ST males to females. We show that SR males are very poor sperm competitors, which is partly related to transfer of fewer sperm during mating. However, sperm numbers alone cannot explain the observed paternity reduction, indicating SR males' sperm may be of reduced quality, possibly due to damage during the killing of the noncarrying Y-sperm. The reduction in sperm competitive ability due to SR is large enough to potentially stabilize the spread of sex ratio drive through populations. The poor sperm competitive ability of SR males coupled with their low fitness as mates could favor increased remating by females to reduce paternity by SR males. Given the generally poor performance of SGE-carrying males in sperm competition, this may generate strong selective pressure favoring polyandry in many species.
The evolution of sex-independent transmission ratio distortion involving multiple allelic interactions at a single locus in rice
4240Koide, YI, M.; Sawamura, N.; Nishimoto, D.; Matsubara, K.; Onishi, K.; Kanazawa, A.; Sano, Y., Genetics, 180:409-420. 2008-01-18 00:00:00.
Transmission ratio distortion (TRD) is frequently observed in inter-and intraspecific hybrids of plants, leading to a violation of Mendelian inheritance. Sex-independent TRD (siTRD) was detected in a hybrid between Asian cultivated rice and its wild ancestor. Here we examined how siTRD is controlled by the S-6 locus via a mechanism in which the S-6 allele acts as a gamete eliminator, and both the male and female gametes possessing the opposite allele (S-6(a)) are aborted only in heterozygotes (S-6/S-6(a)). Fine mapping revealed that the S-6 locus is located neaar the centromere of chromosome 6. Tescross experiments using near-isogenic lines (NILs) carrying either the S-6 or S-6(a) alleles revealed that Asian rice strains frequently harbor an additional allele (S-6(n)) the presence of which, in heterozygotic states (S-6/S-6(n) and S-6(a)/S-6(n)), does not result in siTRD. A prominent reduction in the nucleotide diversity of S-6 or S-6(a) carries relative to that of S-6(n) carries was detected in the chromosomal region. These results suggest that the two incompatible alleles (S-6/S-6(a)) arose independently from S-6(n) and established genetically discontinuous relationships between limited constituents of the Asian rice population.
X chromosome drive
4239Jaenike, J, Current Biology, 18:R508-R511. 2008-01-17 00:00:00.
In the past 10 years, the world record for the men's 100 meter dash has declined from 9.79 to 9.74 seconds, the detection of such small differences being made possible by sophisticated electronic timing devices. If someone were to run the 100 meters in 9.73999 seconds in the 2008 Olympics, would the timers be sensitive enough to show him to be the world's fastest human? Natural selection could, as differences in fitness of that magnitude (10?6) can be detected in species with large effective population sizes. In this way, natural selection can bring about the evolution of exquisitely well-adapted creatures.; Getting back to the race, imagine that one of the runners somehow manages to get a 50-meter head start. With such an advantage, even an overweight, out of shape, or injured athlete could win the gold. An analogous situation applies in evolution. Mendelian segregation, in which the two alleles carried by a heterozygous individual are passed to equal numbers of gametes, ensures that alleles compete fairly and that they succeed (or fail) on the basis of their effects on survival and fertility. Meiotic drive — the process by which alleles are not represented equally in an individual's gametes — subverts the entire process. In the best documented examples of drive, one allele may be passed on to ?100% of an organism's gametes, equivalent to a runner getting a 50-meter head start in the 100 meter dash. The overrepresentation of such alleles in gametes can more than make up for any associated deficiencies in survival and fertility. As a result, these alleles — and those closely linked to them — can rapidly spread through a population, and thus actually cause a decline in the adaptation of a species to its environment. If such an allele drives all the way to fixation, the species may end up a little less well adapted, but there would be no evidence that meiotic drive was the cause, as drive would no longer be expressed.
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.
Small steps or giant leaps for male-killers? Phylogenetic constraints to male-killer host shifts
4257Tinsley, MCM, M. E. N., BMC Evolutionary Biology, 7:e1000313. 2007-01-15 00:00:00.
Background: Arthropods are infected by a wide diversity of maternally transmitted microbes. Some of these manipulate host reproduction to facilitate population invasion and persistence. Such parasites transmit vertically on an ecological timescale, but rare horizontal transmission events have permitted colonisation of new species. Here we report the first systematic investigation into the influence of the phylogenetic distance between arthropod species on the potential for reproductive parasite interspecific transfer. Results: We employed a well characterised reproductive parasite, a coccinellid beetle male-killer, and artificially injected the bacterium into a series of novel species. Genetic distances between native and novel hosts were ascertained by sequencing sections of the 16S and 12S mitochondrial rDNA genes. The bacterium colonised host tissues and transmitted vertically in all cases tested. However, whilst transmission efficiency was perfect within the native genus, this was reduced following some transfers of greater phylogenetic distance. The bacterium's ability to distort offspring sex ratios in novel hosts was negatively correlated with the genetic distance of transfers. Male-killing occurred with full penetrance following within-genus transfers; but whilst sex ratio distortion generally occurred, it was incomplete in more distantly related species. Conclusion: This study indicates that the natural interspecific transmission of reproductive parasites might be constrained by their ability to tolerate the physiology or genetics of novel hosts. Our data suggest that horizontal transfers are more likely between closely related species. Successful bacterial transfer across large phylogenetic distances may require rapid adaptive evolution in the new species. This finding has applied relevance regarding selection of suitable bacteria to manipulate insect pest and vector populations by symbiont gene-drive systems.
A sex-ratio meiotic drive system in Drosophila simulans. II: An X-linked distorter
4255Tao, YA, L.; Kingan, S. B.; Ke, Y.; Xiao, H.; Hartl, D. L., PLOS Biology, 5:2576-2588. 2007-01-13 00:00:00.
The evolution of heteromorphic sex chromosomes creates a genetic condition favoring the invasion of sex-ratio meiotic drive elements, resulting in the biased transmission of one sex chromosome over the other, in violation of Mendel's first law. The molecular mechanisms of sex-ratio meiotic drive may therefore help us to understand the evolutionary forces shaping the meiotic behavior of the sex chromosomes. Here we characterize a sex-ratio distorter on the X chromosome (Dox) in Drosophila simulans by genetic and molecular means. Intriguingly, Dox has very limited coding capacity. It evolved from another X-linked gene, which also evolved de nova. Through retrotransposition, Dox also gave rise to an autosomal suppressor, not much yang (Nmy). An RNA interference mechanism seems to be involved in the suppression of the Dox distorter by the Nmy suppressor. Double mutant males of the genotype dox; nmy are normal for both sex-ratio and spermatogenesis. We postulate that recurrent bouts of sex-ratio meiotic drive and its subsequent suppression might underlie several common features observed in the heterogametic sex, including meiotic sex chromosome inactivation and achiasmy.
Chromosome-wide linkage disequilibrium as a consequence of meiotic drive
4249Dyer, KAC, B.; Jaenike, J., Proceedings of the National Academy of Sciences of the United States of America, 104:1587-1592. 2007-01-07 00:00:00.
Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (X-D). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the X-D chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The X-D is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and X-D in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the XD chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, X-D chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the X-D in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation.
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.
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.
Sex-ratio meiotic drive in Drosophila simulans: cellular mechanism, candidate genes and evolution
4265Montchamp-Moreau, C, Biochemical Society Transactions, 34:562-565. 2006-01-03 00:00:00.
The sex-ratio trait, reported in a dozen Drosophila species, is a type of naturally occurring meiotic drive in which the driving elements are located on the X chromosome. Typically, as the result of a shortage of Y bearing spermatozoa, males carrying a sex-ratio X chromosome produce a large excess of female offspring. The presence of sex-ratio chromosomes in a species can have considerable evolutionary consequences, because they can affect individual fitness and trigger extended intragenomic conflict. Here, I present the main results of the study performed in Drosophilosimulans. In this species, the loss of Y-bearing spermatozoa is related to the inability of the Y chromosome sister-chromatids to separate properly during meiosis II. Fine genetic mapping has shown that the primary sex-ratio locus on the X chromosome contains two distorter elements acting synergistically, both of which are required for drive expression. one element has been genetically mapped to a tandem duplication. To infer the natural history of the trait, the pattern of DNA sequence polymorphism in the surrounding chromosomal region is being analysed in natural populations of D. simulans harbouring sex-ratio X chromosomes. Initial results have revealed the recent spread of a distorter allele.
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.
Degeneration and domestication of a selfish gene in yeast: Molecular evolution versus site-directed mutagenesis
4278Koufopanou, VB, A., Molecular Biology and Evolution, 22:1535-1538. 2005-01-16 00:00:00.
VDE is a homing endonuclease gene in yeasts with an unusual evolutionary history including horizontal transmission, degeneration, and domestication into the mating-type switching locus HO. We investigate here the effects of these features on its molecular evolution. In addition, we correlate rates of evolution with results from site-directed mutagenesis studies. Functional elements have, lower rates of evolution than degenerate ones and higher conservation at functionally important sites. However, functionally important and unimportant sites are equally likely to have been involved in the evolution of new function during the domestication of VDE into HO. The domestication event also indicates that VDE has been lost in some species and that VDE has been present in yeasts for more than 50 Myr.
Genetic linkage between a sexually selected trait and X chromosome meiotic drive
4276Johns, PMW, L. L.; Wilkinson, G. S., Proceedings of the Royal Society B-Biological Sciences, 272:2097-2103. 2005-01-14 00:00:00.
Previous studies on the stalk-eyed fly, Cyrtodiopsis dalmanni, have shown that males with long eye-stalks win contests and are preferred by females, and artificial selection on male relative eye span alters brood sex-ratios. Subsequent theory proposes that X-linked meiotic drive can catalyse the evolution of mate preferences when drive is linked to ornament genes. Here we test this prediction by mapping meiotic drive and quantitative trait loci (QTL) for eye span. To map QTL we genotyped 24 microsatellite loci using 1228 F2 flies from two crosses between lines selected for long or short eye span. The crosses differed by presence or absence of a drive X chromosome, X-D, in the parental male. Linkage analysis reveals that X-D dramatically reduces recombination between X and X-D chromosomes. In the X-D cross, half of the F2 males carried the drive haplotype, produced partially elongated spermatids and female-biased broods, and had shorter eye span. The largest QTL mapped 1.3 cM from drive on the X chromosome and explained 36% of the variation in male eye span while another QTL mapped to an autosomal region that suppresses drive. These results indicate that selfish genetic elements that distort the sex-ratio can influence the evolution of exaggerated traits.
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.
Evolution of divergent DNA recognition specificities in VDE homing endonucleases from two yeast species
4299Posey, KLK, V.; Burt, A.; Gimble, F. S., Nucleic Acids Research, 32:3947-3956. 2004-01-17 00:00:00.
Homing endonuclease genes (HEGs) are mobile DNA elements that are thought to confer no benefit to their host. They encode site-specific DNA endonucleases that perpetuate the element within a species population by homing and disseminate it between species by horizontal transfer. Several yeast species contain the VMA1 HEG that encodes the intein-associated VMA1-derived endonuclease (VIDE). The evolutionary state of VDEs from 12 species was assessed by assaying their endonuclease activities. Only two enzymes are active, PI-ZbaI from Zygosaccharomyces bailii and PI-ScaI from Saccharomyces cariocanus. PI-ZbaI cleaves the Z-bailii recognition sequence significantly faster than the Saccharomyces cerevisiae site, which differs at six nucleotide positions. A mutational analysis indicates that PI-ZbaI cleaves the S.cerevisiae substrate poorly due to the absence of a contact that is analogous to one made in PI-SceI between Gln-55 and nucleotides +9/+10. PI-ZbaI cleaves the Z.bailii substrate primarily due to a single base-pair substitution (A/T+5 --> T/A(+5)). Structural modeling of the PI-ZbaI/DNA complex suggests that Arg-331, which is absent in PI-SceI, contacts T/A(+5), and the reduced activity observed in a PI-ZbaI R331 A mutant provides evidence for this interaction. These data illustrate that homing endonucleases evolve altered specificity as they adapt to recognize alternative target sites.
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.
The distribution of B chromosomes across species
4297Palestis, BGT, R.; Burt, A.; Jones, R. N., Cytogenetic and Genome Research, 106:151-158. 2004-01-15 00:00:00.
In this review we look at the broad picture of how B chromosomes are distributed across a wide range of species. We review recent studies of the factors associated with the presence of Bs across species, and provide new analyses with updated data and additional variables. The major obstacle facing comparative studies of B chromosome distribution is variation among species in the intensity of cytogenetic study. Because Bs are, by definition, not present in all individuals of a species, they may often be overlooked in species that are rarely studied. We give examples of corrections for differences in study effort, and show that after a variety of such corrections, strong correlations remain. Several major biological factors are associated with the presence of B chromosomes. Among flowering plants, Bs are more likely to occur in outcrossing than in inbred species, and their presence is also positively correlated with genome size and negatively with chromosome number. They are no more frequent in polyploids than in diploids, nor in species with multiple ploidies. Among mammals, Bs are more likely to occur in species with karyotypes consisting of mostly acrocentric chromosomes. We find no evidence for an association with chromosome number or genome size in mammals, although the sample for genome size is small. The associations with breeding system and acrocentric chromosomes were both predicted in advance, but those with genome size and chromosome number were discovered empirically and we can offer only tentative explanations for the very strong associations we have uncovered. Our understanding of why B chromosomes are present in some species and absent in others is still in its infancy, and we suggest several potential avenues for future research. 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.
B chromosomes in Sternorrhyncha (Hemiptera, Insecta)
4293Maryanska-Nadachowska, A, Cytogenetic and Genome Research, 106:210-214. 2004-01-11 00:00:00.
In the hemipteroid insects of the suborder Sternorrhyncha, B chromosomes are relatively common in comparison with other suborders of Hemiptera. However, the occurrence of supernumerary chromosomes is restricted, in most cases, to several genera or closely related species. At least in some species of Psylloidea with the XY sex determination system, a mitotically stable B chromosome integrated into an achiasmatic segregation system with the X, and became fixed as a Y chromosome. In some Aphidoidea with a multiple X system of sex determination, B chromosomes appear to be in fact non-functional X chromosomes. Supernumerary chromosomes thus probably play an important role in the evolution of sex determination systems in Sternorrhyncha. Copyright (C) 2004 S. Karger AG, Basel.
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.
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.
Homing endonuclease genes: the rise and fall and rise again of a selfish element
4286Burt, AK, V., Current Opinion in Genetics & Development, 14:609-615. 2004-01-04 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing - in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact - which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.
Genetic dissection of hybrid incompatibilities between Drosophila simulans and D-mauritiana. III. Heterogeneous accumulation of hybrid incompatibilities, degree of dominance, and implications for Haldane’s rule
4317Tao, YH, D. L., Evolution, 57:2580-2598. 2003-01-15 00:00:00.
The genetic basis of Haldane's rule was investigated through estimating the accumulation of hybrid incompatibilities between Drosophila simulans and D. mauritiana by means of introgression. The accumulation of hybrid male sterility (HMS) is at least 10 times greater than that of hybrid female sterility (HFS) or hybrid lethality (HL). The degree of dominance for HMS and HL in a pure D. simulans background is estimated as 0.23-0.29 and 0.33-0.39, respectively; that for HL in an F-1 background is unlikely to be very small. Evidence obtained here was used to test the Turelli-Orr model of Haldane's rule. Composite causes, especially, faster-male evolution and recessive hybrid incompatibilities, underlie Haldane's rule in heterogametic male taxa such as Drosophila (XY male and XX female). However, if faster-male evolution is driven by sexual selection, it contradicts Haldane's rule for sterility in heterogametic-female taxa such as Lepidoptera (ZW female and ZZ male). The hypothesis of a faster-heterogametic-sex evolution seems to fit the current data best. This hypothesis states that gametogenesis in the heterogametic sex, instead of in males per se, evolves much faster than in the homogametic sex, in part because of sex-ratio selection. This hypothesis not only explains Haldane's rule in a simple way, but also suggests that genomic conflicts play a major role in evolution and speciation.
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.
B chromosomes in plants: escapees from the A chromosome genome?
4312Jones, NH, A., Trends in Plant Science, 8:417-423. 2003-01-10 00:00:00.
B chromosomes are dispensable elements that do not recombine with the A chromosomes of the regular complement and that follow their own evolutionary track. In some cases, they are known to be nuclear parasites with autonomous modes of inheritance, exploiting 'drive' to ensure their survival in populations. Their I selfishness' brings them into conflict with their host nuclear genome and generates a host-parasite relationship, with anti-B-chromosome genes working to ameliorate the worst of their excesses in depriving their hosts of genetic resources. Molecular studies are homing in on their sequence organization to give us an insight into the origin and evolution of these enigmatic chromosomes, which are, with rare exceptions, without active genes.
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.
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
4306Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003-01-04 00:00:00.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Adaptation for horizontal transfer in a homing endonuclease
4323Koufopanou, VG, M. R.; Burt, A., Molecular Biology and Evolution, 19:239-246. 2002-01-21 00:00:00.
Selfish genes of no function other than self-propagation are susceptible to degeneration if they become fixed in a population. and regular transfer to new species may be the only means for their long-term persistence. To test this idea we surveyed 24 species of yeast for VDE, a nuclear. intein-associated homing endonuclease gene (HEG) originally discovered in Saccharomyces cerevisiae. Phylogenetic analyses show that horizontal transmission has been a regular occurrence in its evolutionary history. Moreover, VDE appears to be specifically adapted for horizontal transmission. Its 31-bp recognition sequence is an unusually well-conserved region in an unusually well-conserved gene. In addition, the nine nucleotide sites most critical for homing are also unusually well conserved. Such adaptation for horizontal transmission presumably arose as a consequence of selection, both among HEGs at different locations in the genome and among variant,,, at the same location. The frequency of horizontal transmission must therefore be a key feature constraining the distribution and abundance of these genes.
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.
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.
Sex chromosome meiotic drive
4332Jaenike, J, Annual Review of Ecology and Systematics, 32:25-49. 2001-01-10 00:00:00.
Sex chromosome drive refers to the unequal transmission of X and Y chromosomes from individuals of the heterogametic sex, resulting in biased sex ratios among progeny and within populations, The presence of driving sex chromosomes can reduce mean fitness within a population, bring about intragenomic conflict between the X chromosome, the Y, and the autosomes, and alter the intensity or mode of sexual selection within species. Sex chromosome drive, or its genetic equivalent, is known in plants, mammals. and flies. Many species harboring driving X chromosomes have evolved Y-linked and autosomal suppressors of drive. If a drive polymorphism is not stable, then driving chromosomes may spread to fixation and cause the extinction of a species. Certain characteristics of species, such as population density and female mating rate, may affect the probability of fixation of driving chromosomes. Thus, sex chromosome drive could be an agent of species-level selection.
The role of selfish genetic elements in eukaryotic evolution
4331Hurst, GDDW, J. H., Nature Reviews Genetics, 2:597-606. 2001-01-09 00:00:00.
'Selfish genetic elements', such as transposons, homing endonucleases, meiotic drive chromosomes and heritable microorganisms, are common features of eukaryotes. However, their importance in the evolution of eukaryotic genomes is still controversial. In this review, we discuss these diverse elements and their potential importance in the evolution of genetic systems, adaptation, and the extinction and birth of species.
Outcrossed sex allows a selfish gene to invade yeast populations
4329Goddard, MRG, D.; Burt, A., Proceedings of the Royal Society B-Biological Sciences, 268:2537-2542. 2001-01-07 00:00:00.
Homing endonuclease genes (HEGs) in eukaryotes are optional genes that have no obvious effect on host phenotype except for causing chromosomes not containing a cop), of the gene to be cut, thus causing them to be inherited at a greater than Mendelian rate via gene conversion. These genes are therefore expected to increase in frequency in outcrossed populations, but not in obligately selfed populations. In order to test this idea, we compared the dynamics of the VDE HEG in six replicate outcrossed and inbred populations of yeast (Saccharomyces cerevisiae). VDE increased in frequency from 0.21 to 0.55 in four outcrossed generations, but showed no change in frequency in the inbred populations. The absence of change in the inbred populations indicates that any effect of VDE on mitotic replication rates is less than 1%. The data from the outcrossed populations best fit a model in which 82% of individuals are derived from outcrossing and VDE is inherited by 74% of the meiotic products from heterozygotes (as compared with 50% for Mendelian genes), These results empirically demonstrate how a host mating system plays a key role in determining the population dynamics of a selfish gene.
Co-existence of hosts and sex ratio distorters in structured populations
4343Hatcher, MJD, A. M.; Tofts, C., Evolutionary Ecology Research, 2:185-205. 2000-01-21 00:00:00.
Vertically transmitted parasites occur in several invertebrate species, and alter host reproduction by a variety of mechanisms, including sex ratio distortion via feminization. Efficient feminizers are predicted to drive homogenous host populations extinct due to the absence of males. However, group (interdemic) selection may enable host-parasite co-existence through extinction-colonization turnover of local subpopulations. Here we analyse the effects of feminizers on host metapopulations, in relation to the underlying mechanism of host sex determination. We examine host metapopulations with (a) fixed probabilistic sex ratio control, (b) female heterogamety (WZ/ZZ) and (c) male heterogamety (XX/XY) with and without YY viability. Under some circumstances, host and parasite can co-exist in metapopulations despite deterministic instability of local populations, in which case the parasite persists at lower frequency than predicted for homogenous populations. However, co-existence is sensitive to host sex determining mechanism. Long-term co-existence is unlikely in chromosomal systems, where sex ratio selection and novel mating type combinations result in the loss of female-determining alleles from infected host subpopulations. The consequent loss of uninfected females precludes stochastic parasite exclusion and thus prevents local population recovery. Hence, host-feminizer co-existence via interdemic selection requires intrinsic patch recovery in addition to recolonization from neighbouring subpopulations. We conclude that metapopulation structure can only buffer host populations against parasite-mediated extinction if female-determining alleles are retained in the host population.
Persistence of selfish genetic elements: population structure and conflict
4342Hatcher, MJ, Trends in Ecology & Evolution, 15:271-277. 2000-01-20 00:00:00.
Selfish genetic elements are vertically transmitted factors that spread by obtaining a transmission advantage relative to the rest of the genome of their host organism, often with a cost to overall host fitness. In many cases, conventional population genetics theory predicts them spreading through populations, reaching fixation and becoming undetectable or sometimes driving the population extinct. However, in several well studied systems, these genetic elements are known to persist at relatively low, stable frequencies. Recent research suggests that several processes might explain these observations, including population structure, intragenomic conflict and coevolution.
Models of sex-ratio meiotic drive and sexual selection in stalk-eyed flies
4358Lande, RW, G. S., Genetics Research, 74:245-253. 1999-01-16 00:00:00.
Hypertrophied sexually dimorphic eye stalks have evolved independently in several families of Diptera, with the eyespan of males exceeding their total body length in some species. These structures function in intermale contests for territories and in mate attraction, the classical mechanisms of sexual selection. In the family Diopsidae, species with extremely exaggerated eye stalks and marked sexual dimorphism in relative eyespan also usually have strongly female-biased sex ratios in nature caused by X-linked meiotic drive, whereas species with relatively small eye stalks have little or no sexual dimorphism, often lack meiotic drive and have even sex ratios. We investigate the possible connection between sexual selection and sex-ratio meiotic drive by analysing a three-locus model for the evolution of female choice for a male character associated with meiotic drive. Both meiotic drive and the male character are X-linked and the female preference is autosomal. Our model shows that suppressed recombination between meiotic drive and the male character, e.g. by inversion of the X chromosome, is necessary for sex-ratio selection to promote the origin of female mating preferences and exaggerated secondary sexual characters. With complete suppression of recombination, sexual selection reduces the frequency of meiotic drive, and may eliminate it. Very rare recombination, gene conversion or mutation, at rates characteristic of chromosome inversions in Drosophila, restores the meiotic drive polymorphism to its original equilibrium. Sex-ratio meiotic drive may thus act as a catalyst accelerating the origin of female mating preference and exaggerated male traits.
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.
Suppression of sex-ratio meiotic drive and the maintenance of Y-chromosome polymorphism in Drosophila
4356Jaenike, J, Evolution, 53:164-174. 1999-01-14 00:00:00.
Like several other species of Drosophila, D. quinaria is polymorphic for X-chromosome meiotic drive; matings involving males that carry a "sex-ratio" X chromosome (X(SR)) result in the production of strongly female-biased offspring sex ratios (Jaenike 1996). A survey of isofemale lines of D, quinaria from several populations reveals that there is genetic variation for partial suppression of this meiotic drive. Crossing experiments show that there is Y-linked. and probably autosomal, variation for suppression of drive. Y-linked suppressors of X-chromosome drive have now been described in several species of Diptera. I develop a simple model for the maintenance of Y-chromosome polymorphism in species polymorphic for X-linked meiotic drive. One interesting feature of this model is that, if there is a stable Y-chromosome polymorphism, then the equilibrium frequency of the standard and sex-ratio X chromosomes is determined solely by Y-chromosome parameters, not by the fitness effects of the different X chromosomes on their carriers. This model suggests that Y-chromosome polymorphism may be easier to maintain than previously thought, and I hypothesize that karyotypic variation in Y chromosomes will be found to be associated with suppression of sex-ratio meiotic drive in other species of Drosophila.
Invasion of one insect species, Adalia bipunctata, by two different male-killing bacteria
4355Hurst, GDDvdS, J. H. G.; Majerus, T. M. O.; Bertrand, D.; Zakharov, I. A.; Baungaard, J.; Volkl, W.; Stouthamer, R.; Majerus, M. E. N., Insect Molecular Biology, 8:133-139. 1999-01-13 00:00:00.
Male-killing bacteria, which are inherited through the female line and kill male progeny only, are known from five different orders of insect. Our knowledge of the incidence of these elements has stemmed from discovery of their phenotype in different species, Our estimate of the frequency with which insects have been invaded by these elements therefore depends on each observation of the male-killing phenotype within a species being associated with a single microorganism. We here record an example of a single insect species being infected with two taxonomically distinct male-killing bacteria. Western European populations of the two-spot ladybird, Adalia bipunctata, have previously been shown to bear a male-killing Rickettsia, However, we here show that the majority of the male-killing lines tested from Central and Eastern Europe do not bear this bacterium. Rather, 16S rDNA sequence analysis suggests male-killing is associated with st member of the genus Spiroplasma. We discuss this conclusion in relation to the evolutionary genetics of male-killing bacteria, and the evolution of male-killing behaviour in the eubacteria.
Population dynamics under parasitic sex ratio distortion
4354Hatcher, MJT, D. E.; Dunn, A. M.; Tofts, C., Theoretical Population Biology, 56:11-28. 1999-01-12 00:00:00.
We analyse the population dynamic effects of sex ratio distortion by vertically transmitted, feminizing parasites, We show that, for diploid hosts, sex ratio distortion may lead to extinction as males become too rare to maintain the host population through reproduction. Feminizers can magnify Allee effects, broadening the range of conditions leading to extinction of small populations, Depending on male mating constraints and strength of density dependence, feminizers may either increase or decrease the equilibrium host density. Under conditions leading to deterministic host extinction, stochastic elimination of the parasite may allow the host population to recover. Hence, infection by parasitic sex ratio distorters may be transient in finite populations. We consider the implications of this process for parasite prevalence, host population regulation, and sex ratio evolution. (C) 1999 Academic Press.
Recurrent invasion and extinction of a selfish gene
4353Goddard, MRB, A., Proceedings of the National Academy of Sciences of the United States of America, 96:13880-13885. 1999-01-11 00:00:00.
Homing endonuclease genes show super-Mendelian inheritance, which allows them to spread in populations even when they are of no benefit to the host organism. To test the idea that regular horizontal transmission is necessary for the long-term persistence of these genes, we surveyed 20 species of yeasts for the omega-homing endonuclease gene and associated group I intron. The status of omega could be categorized into three states (functional, nonfunctional, or absent), and status was not clustered on the host phylogeny. Moreover, the phylogeny of w differed significantly from that of the host, strong evidence of horizontal transmission. Further analyses indicate that horizontal transmission is more common than transposition, and that it occurs preferentially between closely related species. Parsimony analysis and coalescent theory suggest that there have been 15 horizontal transmission events in the ancestry of our yeast species, through simulations indicate that this value is probably an underestimate. Overall, the data support a cyclical model of invasion, degeneration, and loss, followed by reinvasion, and each of these transitions is estimated to occur about once every 2 million years. The data are thus consistent with the idea that frequent horizontal transmission is necessary for the long-term persistence of homing endonuclease genes, and further, that this requirement limits these genes to organisms with easily accessible germ lines. The data also show that mitochondrial DNA sequences are transferred intact between yeast species; if other genes do not show such high levels of horizontal transmission, it would be due to lack of selection, rather than lack of opportunity.
Are Drosophila SR drive chromosomes always balanced?
4351Carvalho, ABV, S. C., Heredity, 83:221-228. 1999-01-09 00:00:00.
SR chromosomes are the best-known case of sex chromosome meiotic drive. These X chromosomes cause the production of female-biased progenies in several Drosophila species; Due to their meiotic drive advantage, they are expected to spread and become fixed, resulting in population extinction due to the lack of males. However, this apparently does not occur: SR chromosomes are maintained in balanced polymorphisms, resulting from the equilibrium between their meiotic drive advantage and deleterious fitness effects. In this paper we review the current explanations for their deleterious effects and we argue that it is highly improbable that all newly emerged SR are sufficiently deleterious to avoid fixation. Unbalanced SR almost certainly arise and go unnoticed because of three possible outcomes: (i) fixation followed by extinction of the population or species; (ii) fixation followed by the emergence and fixation of drive suppressors, restoring the normal 1:1 sexual proportion; or (iii) transformation into balanced SR due to partial suppression. If these outcomes really occur, then extant cases of sex-chromosome meiotic drive such as SR, causing small deviations on the population sexual proportion are only the tip of the iceberg and strong sexual proportion shifts (possibly followed by extinction) are a more common feature of species evolution than is usually assumed.
Evolution of driving X chromosomes and resistance factors in experimental populations of Drosophila simulans
4350Capillon, CA, A., Evolution, 53:506-517. 1999-01-08 00:00:00.
Sex-ratio drive is a particular case of meiotic drive, described in several Drosophila species, that causes males bearing driving X chromosome to produce a large excess of females in their progeny. In Drosophila simulans, driving X chromosomes and resistance factors located on the Y chromosome and on the autosomes have been previously reported. In this paper, we report the study of the dynamics of sex-ratio factors in experimental populations. We followed the evolution in frequency of driving X chromosomes in the absence of resistance factors and the evolution of resistance factors in the presence of driving X chromosomes. The driving X chromosome was lost, contrarily to theoretical expectations that predict its rapid invasion. Autosomal resistances increased in frequency, and resistant Y chromosomes invaded the population very quickly, as predicted by theoretical models. Fitness measurements showed that the loss of the driving X chromosome was due to a strong deleterious effect that was expressed only when distorting males were in competition with standard males. However, the spread of autosomal resistances reduced this deleterious effect. Implications for the maintenance of polymorphism in natural populations are discussed.
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).
Sex determination, sex ratios, and genetic conflict
4378Werren, JHB, L. W., Annual Review of Ecology and Systematics, 29:233-261. 1998-01-16 00:00:00.
Genetic mechanisms of sex determination are unexpectedly diverse and change rapidly during evolution. We review the role of genetic conflict as the driving force behind this diversity and turnover. Genetic conflict occurs when different components of a genetic system are subject to selection in opposite directions. Conflict may occur between genomes (including paternal-maternal and parental-zygotic conflicts) or within genomes (between cytoplasmic and nuclear genes or sex chromosomes and autosomes). The sex-determining system consists of parental sex-ratio genes, parental-effect sex determiners, and zygotic sex determiners, which are subject to different selection pressures because of differences in their modes of inheritance and expression. Genetic conflict theory is used to explain the evolution of several sex-determining mechanisms, including sex chromosome drive, cytoplasmic sex-ratio distortion, and cytoplasmic male sterility in plants. Although still limited, there is growing evidence that genetic conflict could be important in the evolution of sex-determining mechanisms.
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.
The dynamics of maternal-effect selfish genetic elements
4376Smith, NGC, Journal of Theoretical Biology, 191:173-180. 1998-01-14 00:00:00.
Maternal-effect selfish genes such as Medea or Seat act to kill progeny that do not bear a copy of the selfish gene present in the mother. Previous models of this system allowed for two types of allele, the selfish (killer) type and the sensitive (susceptible) wild-type. These models predict that the invasion conditions of the selfish allele are quite broad and that if invasion is possible a high frequency equilibrium is to be expected. The selfish element is therefore predicted to persist. Here a hypothetical third allele that neither kills nor is killed (i.e, insensitive) is considered. Such an allele could enter a population by recombination, mutation or migration. The incorporation of this third allele profoundly affects the dynamics of the system and, under some parameter values, it is possible for the spread of the insensitive allele to lead, eventually, to the fixation of the wild-type allele (reversible evolution). This is most likely if the death of progeny provides no direct benefit to the surviving sibs (i.e. in the absence of fitness compensation), as in insects without gregarious broods. Under these circumstances the selfish element cannot spread when infinitely rare, only after having risen to some finite frequency. A fitness cost to bearing the killer allele then causes its loss. However, if fitness compensation is found (e.g, in placental mammals) the invasion of the selfish element from an infinitely low level is possible for a wide range of costs and both stable coexistences of all three alleles and limit cycles of all three are then found. It is therefore to be expected that in mammals selfish maternal-effect genes are more likely both to spread and to persist than in insects, due to their different levels of fitness compensation. (C) 1998 Academic Press Limited.
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 genetic elements and speciation
4371Hurst, GDDS, M., Heredity, 80:2-8. 1998-01-09 00:00:00.
This review concerns the importance of selfish genetic elements (SGEs) in speciation. We assess the importance of medea genes, meiotic drive elements, transposable elements and the bacterium Wolbachia in the creation of postzygotic isolation. Although all of these elements can contribute to postzygotic isolation, their contribution will often disappear if there is gene flow between the populations. Further, there is the possibility that incompatibilities produced by SGEs may lessen over time. We conclude that although some of the case studies are tantalizing, particularly those associated with Wolbachia, the role of selfish genetic elements in speciation remains unproven.
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.
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 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.
Meiotic drive an Myotonic Dystrophy – Reply
4404Carey, NJ, K.; Nokelainen, P.; Peltonen, L.; Savontaus, M. L.; Juvonen, V.; Anvret, M.; Grandell, U.; Chotai, K.; Robertson, E.; Middletonprice, H.; Malcolm, S., Nature Genetics, 10:133-133. 1995-01-02 00:00:00.
Myotonic dystrophy (DM) is a trinucleotide disorder and in sub-clinical individuals there is considerable variation in the length of the CTG repeat. Two groups have recently analysed the patterns of segregation of different sized alleles at this locus and both report an excess of the longer version of the allele in the progeny of sub-clinical individuals1•2• This excess they claim to be due to meiotic drive1•2• Our re-analysis of these two studies indic
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 evolution of lethals in the t-haplotype system of the mouse
4411Charlesworth, B, Proceedings of the Royal Society B-Biological Sciences, 258:101-107. 1994-01-09 00:00:00.
The evolution of lethal haplotypes in the t-haplotype segregation distortion system of Mus is examined by mathematical and computer models. The models assume that there is reproductive compensation for the loss of lethal embryos, such that the net reproductive success of a female is not reduced in proportion to the frequency of lethal offspring which she produces. The initial population consists of a mixture of wildtype and homozygous male-sterile t-haplotypes. The failure of sterile males to reproduce may cause a higher fitness cost to mothers heterozygous for t-haplotypes than does elimination of a recessive lethal. Under certain conditions, a recessive lethal will spread and come to a polymorphic equilibrium. Wildtype, lethal and non-lethal haplotypes are all present at this equilibrium. Ifa second lethal mutation arises on a non-lethal t-haplotype in such an equilibrium population, it will increase in frequency and eventually displace the non-lethal t-haplotypes. A third lethal t-haplotype introduced at a low frequency into an equilibrium with two lethals can sometimes be selected for, although this is less likely if compensation is strong. The theoretical predictions are compared with data on natural populations.
Hypothetical sisterkiller
4409Butcher, DLD, H. W., Nature, 369:26-26. 1994-01-07 00:00:00.
It was premature of Hurst in his News and Views article I to accept Haig's claim2 that a hypothetical meiotic drive element, SisterKiller, can lead to evolution from one-step to multi-step meiosis. The basis of Haig's claim is that a SisterKiller allele that causes a gamete to kill its sister gamete can invade and go to fixation in a population using one-step meiosis, whereas in a population using multi-step meiosis, Sister Killer cannot invade. Hurst concludes that SisterKiller could have caused the evolution of multi-step meiosis. The conditions under which this is true are more restrictive than Haig suggests.
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.
The evolution of unusual chromosomal systems in coccoids: Extraordinary sex-ratios revisited
4424Haig, D, Journal of Evolutionary Biology, 6:69-77. 1993-01-02 00:00:00.
Coccoids (scale insects) exhibit a wide variety of chromosomal systems. In many species, paternal chromosomes are eliminated from the male germline such that all of a male's sperm transmit an identical set of maternal chromosomes. In such species, an offspring's sex is determined by whether or not paternal chromosomes are inactivated in the egg's cytoplasm after fertilization. This paper presents a model of the evolution of paternal genome loss in coccoids from an ancestral system of XX-XO sex determination. The model is based on Hamilton's (1967) theory that different genetic elements within the genome have different unbeatable sex ratios. In this model (1) meiotic drive by the X chromosome in XO males causes female-biased sex ratios; (2) the maternal set of autosomes in males evolves effective sex linkage to exploit X-drive; and (3) genes expressed in mothers are selected to convert some of their XX daughters into sons. A similar model may explain the evolution of haplodiploidy.
Evolution of the mouse t-haplotype – Recent and worldwide introgression to Mus musculus
4433Morita, TK, H.; Murata, K.; Nozaki, M.; Delarbre, C.; Willison, K.; Satta, Y.; Sakaizumi, M.; Takahata, N.; Gachelin, G.; Matsushiro, A., Proceedings of the National Academy of Sciences of the United States of America, 89:6851-6855. 1992-01-11 00:00:00.
Mouse t haplotypes are variants of chromosome 17, consisting of four inversions. Despite the homozygous lethality and pleiotropic effect on embryonic development, sperm production, and recombination, they have widely spread in natural populations of the house mouse (10-40% in frequency) because of the meiotic drive advantage. We sequenced 14 Tcp-1 (t-complex polypeptide 1) genes from four t haplotypes, nine wild mice, and a rat as a reference. From a comparison of intron sequences of 610 base pairs, we dated the origin of t haplotypes to 2.9 +/- 0.7 million years ago, which predates the splitting of Mus musculus subspecies (almost-equal-to 1 million years ago). However, the Tcp-1 intron sequences of t haplotypes from different M. musculus subspecies from various parts of the world show no divergence, indicating the recent introgression (no earlier than 0.8 million years ago) of a single ancestral type. Nucleotide changes in coding regions are also consistent with this conclusion. Hence, polymorphisms among t haplotypes including lethality factors have accumulated during this short time period independently in each M. musculus subspecies.
Can transposable elements be used to drive disease refractoriness genes into vector populations?
6271M. G. Kidwell and J. M. C. Ribeiro, Parasitology Today, 8:325-329. 1992-01-08 16:40:55.
A number of biological procedures are currently being considered as alternatives to insecticide-based methods for the control of insect vectors of disease. Among these are the adaptation of various genetic mechanisms to drive genes of interest, such as refractoriness to malaria in mosquitoes, into natural populations, for vector control purposes. Here, Margaret Kidwell and Jose Ribeiro develop a rationale for the possible use of transposable genetic elements, one of these potential drive mechanisms, and some of the problems being faced in seeking to determine the feasibility of such a strategy are described.
Genetic scrambling as a defense against meiotic drive
4443Haig, DG, A., Journal of Theoretical Biology, 153:531-558. 1991-01-21 00:00:00.
Genetic recombination has important consequences, including the familiar rules of Mendelian genetics. Here we present a new argument for the evolutionary function of recombination based on the hypothesis that meiotic drive systems continually arise to threaten the fairness of meiosis. These drive systems act at the expense of the fitness of the organism as a whole for the benefit of the genes involved. We show that genes increasing crossing over are favoured, in the process of breaking up drive systems and reducing the fitness loss to organisms.
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.
X-chromosome segregation distortion in Drosophila
4439Curtsinger, JW, American Naturalist, 137:344-348. 1991-01-17 00:00:00.
The sex-ratio trait exhibits both discrete and continuous variation in Drosophila pseudoobscura. The discrete variation is caused by X-chromosome meiotic drive. The evolutionary forces maintaining the meiotic-drive polymorphism include strong viability selection against homozygous females and virility selection in males. The relative importance of the two factors is unresolved. The evidence for a genetic component in the continuous sex-ratio variation comes from artificial-selection experiments, large-scale estimation of segregation ratios corrected for viability effects, and an examination of the rates of spermatid loss. Segregation ratio can be treated as a typical quantitative character subject to major and minor genetic modifiers.
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.
Sex ratio polymorphism in Drosophila pseudoobscura
4436Beckenbach, AT, American Naturalist, 137:340-343. 1991-01-14 00:00:00.
I studied "sex-ratio" (SR) genotype frequencies in two populations of Drosophila pseudoobscura from southeastern Arizona: Bear Creek Canyon and Tucson. Wild-inseminated females were collected, their fecundities measured in the laboratory, and their SR genotypes inferred by cytological analysis of their progenies. A statistically significant fecundity deficiency was observed among SR/SR females from Bear Creek Canyon. The SR frequency in the Tucson population increased at a rate consistent with the operation of meiotic drive unopposed by selection.
B-chromosome drive
4445Jones, RN, American Naturalist, 137:430-442. 1991-01-03 00:00:00.
The view of B-chromosome polymorphisms that is coming into favor resembles the so-called "parasitic" model, which was first advanced 45 yr ago. Since that time, repeated and ongoing efforts have been made to ascribe an adaptive role to B's (e.g., in terms of phenotypic advantage, effects of variability, etc.), but success in this direction has been singularly lacking. Consistently and repeatedly, the data indicate that harmful effects, or at best neutral or undetectable effects, are associated with B's and provide evidence of the potency of accumulation mechanisms based on drive. Modeling exercises have proved useful in examining these polymorphisms, and of the ones that have been published to date, all have favored drive as the main force generating B-chromosome polymorphisms.
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.
Sex-ratio meiotic drive in Drosophila testacea
4462James, ACJ, J., Genetics, 126:651-656. 1990-01-20 00:00:00.
We document the occurrence of "sex ratio" meiotic drive in natural populations of Drosophila testacea. "Sex ratio" males sire greater than 95% female offspring. Genetic analysis reveals that this effect is due to a meiotically driven X chromosome, as in other species of Drosophila in which "sex ratio" has been found. In contrast to other drosophilids, the "sex ratio" and standard chromosomes of D. testacea do not differ in gene arrangement, implying that the effect may be due to a single genetic factor in this species. In all likelihood, the "sex ratio" condition has evolved independently in D. testacea and in the Drosophila obscura species group, as the loci responsible for the effect occur on different chromosomal elements. An important ecological consequence of "sex ratio" is that natural populations of D. testacea exhibit a strong female bias. Because D. testacea mates, oviposits, and feeds as adults and larvae on mushrooms, this species provides an excellent opportunity to study the selective factors in nature that prevent "sex ratio" chromosomes from increasing to fixation and causing the extinction of the species.
Evolution of the segregation ratio – Modification of gene conversion and meiotic drive
4461Bengtsson, BOU, M. K., Theoretical Population Biology, 38:192-218. 1990-01-19 00:00:00.
We compare the evolutionary pressures that direct the modification of gene conversion and meiotic drive at loci subject to purifying and overdominant viability selection. Gene conversion differs from meiotic drive in that modifers do not affect their own segregation ratios, even when linked to the viability locus. Segregation distortion generates gametic level disequilibria between alleles at the viability locus and modifiers of gene conversion and meiotic drive: enhancers of segregation distortion become positively associated with driven alleles. Suppression of gene conversion evolves if the driven allele is marginally disadvantageous (overdominant viability selection), and higher rates evolve if the driven alleles are relatively advantageous (purifying viability selection). Gametic disequilibria permit enhancers of meiotic drive that are linked to the driven locus to promote their own segregation. We attribute the failure of genetic modifiers of gene conversion and meiotic drive to maximinize mean fitness to the generation of such associations.
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
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.
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 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.
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.
Sex-ratio trait in Drosophila pseudoobscura – Fertility relations of males and meiotic drive.
4483Beckenbach, AT, American Naturalist, 112:97-117. 1978-01-21 00:00:00.
In the early analysis of the "sex-ratio" polymorphism (SR) of Drosophila pseudoobscura, complete meiotic drive was assumed, and study centered on the nature of the selective forces opposing its spread. Policansky and Ellison (1970) found that the mechanism of SR involved the degeneration of half the spermatids during spermatogenesis. They suggested that little or no drive may be expressed due to a fertility deficiency of SR males. Thus little or no selection is required to balance the drive. I report studies conducted to determine the conditions under which either of these alternatives might hold. Virgin females were mated once to either SR or ST (standard) males aged as virgins for 3 days, and their fecundities were determined by daily egg counts. No differences were found between the two groups in either daily egg production or egg-to-adult survival of the progenies. Only females maintained with males throughout the experiment were clearly superior in these parameters. No fertility differences between SR and ST males are unconditional. Fertilities of males aged for varying lengths of time as virgins were determined by mating them to as many virgin females as they would inseminate in a brief span of time. Time periods ranged from 3 to 8 h, depending on the ages of the males. Fertility of the SR males was lower than that of ST males of the same age for males aged 20-33 h from eclosion. Differences in 4-day-old males were not so clear. When 4-day-old males which had depleted their stores of sperm by repeated matings were retested after 12 h of rest, SR males again showed lower fertility than ST males. The fertility reduction of SR males occurs only during the first few days as adults or after repeated matings. The effect of different degrees of insemination on the pattern of production of fertile eggs was examined by mating virgin females to males which were either virgin (heavy insemination) or with seminal vesicles partially depleted by three previous matings (light insemination). No differences in either fecundity or hatchability between the groups were observed early in the reproductive period, but the hatchability of the eggs produced by the lightly inseminated females declined sooner than that of the heavily inseminated group. This response would minimize the populational consequences of fertility differences in males unless the females remate. It is suggested that the conditional fertility differences between SR and ST males are of little consequence until the females remate. Depending on the time of remating, there is potentially a wide range in the amount of meiotic drive expressed.
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.
Analysis of a general population genetic model of meiotic drive
4501Hartl, DL, Evolution, 24:538-545. 1970-01-19 00:00:00.
The purpose of this article is to present the detailed solution of a model of meiotic drive which Lewontin (1968) has suggested would be helpful in understanding the evo- lutionary dynamics of the t-alleles in the house mouse. Because mice tend to breed in small endogamous family units, however, the deterministic model is only a very rough approximation to what would be expected to occur in nature, and to gain better insight one is forced to undertake Monte Carlo simulation of small populations (Lewontin and Dunn, 1960; Lewontin, 1968).
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.
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.
Genetic distortion of sex ratio in a mosquito Aedes aegypti
4505Hickey, WAC, G. B., Genetics, 53:1177-1196. 1966-01-03 00:00:00.
CRAIG, HICKEY and VANDEHEY (1960) reported that a hereditary factor transmitted by males was responsible for high male ratios in A. aegypti. This phenomenon was designated as male-producing or MP. Males from high maleproducing families produced a high proportion of males in their own progeny, regardless of the type of female to which they were crossed. This condition was not due to selective mortality, at least in postgametic stages. In 1960, nothing was known about the sex-determining mechanism in A. aegypti. In addition, the male-producing lines available for study were highly variable in expression. These factors hampered more precise analysis of the mechanism of inheritance of MP. The present work was initiated because new crosses with different strains gave more pronounced and predictable distortion of sex ratios. Earlier strains gave about 15 to 30% female, whereas present lines produce about 0 to 15% female. This paper presents an analysis of the mode of inheritance of MP. In addition, data suggesting the mechanism of action are included. Separate reports will be published elsewhere on ( 1 ) the distribution and behavior of MP in experimental populations and (2) the effect of environment on expression of MP. A more detailed account of some of this work is given by HICKEY (1965a, b). Nomenclature used ih these preliminary reports is superseded by that in the present work.
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.
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 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.
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