Keywords: Selfish genetic elements
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.
Discovery of a Genetic Toxin-Antidote System in Vertebrates
35490Duilio Mazzoni Zerbinato A Silva, Morgan Skinner, Takaya Totsuka, et al., bioRxiv, 2026-03-06 10:25:21.
Toxin-antidote (TA) systems are selfish genetic elements that bias their own inheritance by coupling a toxin that kills daughter cells or offspring with an antidote that specifically rescues those with the TA. TAs are a widespread phenomenon, observed in bacteria, fungi, plants, and invertebrate animals, but have not yet been described in vertebrates. Here we report the first known vertebrate TA system that sabotages mammalian embryogenesis. The HSR locus on mouse chromosome 1 is a selfish genetic element that biases its transmission through the female germline. When HSR heterozygous females are crossed with wild-type males, wild-type embryos show high mortality, leading to preferential survival of embryos with HSR. The mechanism underlying embryo killing was unknown. We find that HSR kills wild-type post implantation embryos by depositing a toxin (SP100) that induces significant DNA damage. Embryos with HSR also inherit the toxin but survive by expressing an antidote (SP110) that blocks the effects of the toxin. Our findings reveal a previously unrecognized genetic cheating strategy in vertebrates and demonstrate its impact on mammalian reproduction.
Is a ‘selfish gene’ making a Utah family have twice as many boys as girls?
35478Ewen Callaway, Nature, 2026-02-27 18:24:37.
By sifting through an anonymized genealogy database, researchers have discovered a Utah family that has been having twice as many boys as girls for seven generations. It is the first clear evidence that humans might have ‘selfish genes’ that distort the sex ratio of offspring from roughly 50:50, the researchers argue in a preprint posted on bioRxiv earlier this month. The findings have not been peer-reviewed. Such sex ‘distorters’ have been discovered — and studied in great depth — in laboratory animals such as mice and flies, in which their effects can be detected through selective breeding. “If you look, more often than not, you find them,” says Nitin Phadnis, an evolutionary geneticist at the University of Utah in Salt Lake City, who co-led the study. Theoretical predictions suggest that sex distorters probably do exist in people as well, and that they could produce excesses of biological boys or girls at birth. But humans’ long generation times and low birth rates as well as ethical issues have made such genes — and other ‘selfish’ genetic elements , meaning that they bias their own transmission to future generations whether or not they improve an individual’s biological fitness — difficult to spot.
Upper bound on the mutational burden imposed by a CRISPR-Cas9 gene-drive element
35463Michael S Overton, Sean E Guy, Xingsen Chen, et al., G3 Genes|Genomes|Genetics, 2026-02-18 10:08:37.
Homing-based CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, with applications from disease eradication to species conservation. However, Cas9 alone and in a complex with guide RNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to unintended loss-of-heterozygosity (LOH) events. These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To measure 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. We found no detectable effects on the genome-wide rates of mutations or LOH events. Our power calculations suggest that CCGD or Cas9 affect these rates by less than 30%, which is much less than natural variation for these traits in yeast. A more detailed examination shows that CCGD or Cas9 may alter the lengths and genomic distributions of LOH events, but the statistical support for these effects is weak. Thus, our results demonstrate that CCGDs impose at most a weak additional mutational burden in the yeast model. Although mutagenic effects of gene drives need to be further evaluated in other systems, our results add credence to the proposition that the evolutionary risks posed by well-designed gene drives may be acceptable.
Signatures of sex ratio distortion in humans
35441James Guy Baldwin-Brown, Sergiusz Wesolowski, Raquel Mae Reisinger, et al., bioRxiv, 2026-02-10 18:42:47.
Segregation distortion, the disproportionate inheritance of selfish genetic elements, is an important evolutionary force. While many species carry distorters, it is not clear if humans do. Major limitations for detecting human distortion are the small size of human families and the lack of genetic markers in most subjects. Here, we present evidence of strong distortion in a large human pedigree. We analyzed pedigrees from the Utah Population Database and identified lineages with a high chance of carrying a distorter. In particular, we identified a family that preferentially produced male offspring at a 2:1 ratio. This pattern is consistent with a distorting Y-chromosome, a rarity in species with degenerate Y-chromosomes. The detection of such non-Mendelian inheritance patterns suggests that human genomes may harbor segregation distorters.
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.
D. melanogaster meiotic driver Stellate compromises sperm development by impeding a process of nuclear envelope remodeling
35390Xuefeng Meng, Yukiko M Yamashita,, Genetics, 2026-01-23 09:55:19.
Meiotic drive is a phenomenon that violates Mendel’s Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that components of the nuclear lamina (such as Lamin Dm0, and the LEM domain proteins Otefin and Bocks) are rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatids retained these nuclear lamina proteins for a prolonged time. Their delayed removal is associated with defective formation of the dense complex, which is composed of a bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatids led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.
Targeted editing of pericentromeric satellite DNA alters sensitivity to meiotic drive
35388Danna G. Eickbush, Jabale Rahmat, Matthew Lindsay, et al., bioRxiv, 2026-01-21 16:51:02.
Eukaryotic genomes are abundant in satellite DNA (satDNA): large blocks of tandemly-repeated sequences that accumulate in heterochromatic genome regions. SatDNAs are dynamic in their genomic location and abundance across species. Some satDNAs overlap essential genome regions such as centromeres and telomeres, but even pericentromeric satDNA can have effects on phenotypes, raising questions about their functional significance. However, it remains unclear whether these effects depend on satDNA sequence, copy number, higher-order structural organization, or genomic context. The highly repetitive nature of satDNA arrays has long hindered detailed genomic and genetic analyses. Recent advances in long-read sequencing now facilitate both the detailed characterization of satDNA structure and the development of more targeted approaches to genetic analysis. Here we present a sequential CRISPR/Cas9-based strategy to make mutations in satDNA arrays and demonstrate its utility using an autosomal pericentromeric satDNA in Drosophila melanogaster called Responder (Rsp). Rsp is the target of a sperm-killing male meiotic driver, Segregation Distorter (SD), where sensitivity to sperm killing positively correlates with Rsp copy number. Using our CRISPR/Cas9 approach, we generated an allelic series of Rsp deletion and expansion variants in two genetic backgrounds and examined their effects on spermatogenesis. Our approach produced precise satDNA variants efficiently, with minimal detectable off-target effects. The resulting mutations affect sensitivity to SD that scale with Rsp copy number. This work establishes a new framework for experimentally dissecting satDNA function and provides insights into the evolutionary and functional roles of satDNA in genome organization.
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.
A male-transmitted B chromosome undergoes strong meiotic drag in females of the jewel wasp Nasonia vitripennis
35373Ferree PM, Cummings J, Garman E, Solomon J, Martinez KS, PLoS Biol, 24. 2026-01-16 16:24:20.
Many organisms carry extra, non-essential chromosomes known as B chromosomes (Bs), which are selfishly transmitted at super-mendelian levels to offspring. This heightened transmission, termed drive, occurs during gametogenesis, usually in one of the two parents. In some cases, Bs can experience an opposing process, drag, which reduces their transmission. If these processes occur together in the same organism, one in each parental sex, then they may facilitate the spread of Bs while countering their accumulation in the genome to harmful levels. While previous studies have elucidated mechanistic aspects of B drive, little is known about drag or other factors that govern the inheritance of these selfish genetic elements. Here, we examined the inheritance of Paternal Sex Ratio (PSR), a single-copy B in the jewel wasp, Nasonia vitripennis, which is transmitted paternally to offspring. PSR drives by converting female-destined embryos into PSR-transmitting males. Using genetic manipulation, we produced exceptional PSR-carrying females, which were used to assess B transmission potential. We found that females transmit PSR at an unexpectedly low level compared to univalent chromosomes in other organisms. This reduced transmission stems from remarkable loss of PSR from the egg’s nucleus upon entry into meiosis, an effect that may be caused by an absence of microtubule-based spindle fibers in meiosis I-arrested wasp eggs. We also found that PSR is strictly limited to a single copy per genome, likely because wasps having two PSR copies die during development. Our findings reveal the successful inheritance of this selfish B chromosome involves its restriction to a single copy and hidden female meiotic drag in addition to strong paternal drive.
A systematic review and critical analysis of the evidence for transmission ratio distortion in humans
35379Ziyi Dai, Gregory Costain, Genetics, 2026-01-14 16:36:37.
Mendel's law of equal segregation states that during gamete formation, the 2 alleles at a gene locus segregate such that each gamete has an equal probability of containing either allele. Transmission ratio distortion (TRD) occurs when 1 of the 2 alleles from either parent is preferentially transmitted to the offspring, resulting in a deviation from the expected 1:1 ratio. Although TRD has been observed and studied in nonhuman species, the full extent and underlying biology of TRD in humans remains poorly summarized. Here we present a systematic review to assess evidence of TRD in the human genome, tracing reports from the 1970s through 2025. Overall, 96 studies including 42 different human variants/genes/loci met inclusion criteria. These studies provided only preliminary and/or conflicting evidence of TRD. Study methods were limited by multiple recurrent biases. Experimental validation of the biological mechanism(s) underlying the putative distortion was rarely performed or possible. TRD warrants renewed attention in the field of human genetics, especially with the growing availability of very large, family-based genome-wide sequencing datasets.
Selfish chromosomes exploit a germline checkpoint to eliminate competing gametes
35349Ridges, J.T., Bladen, J., King, T.D. et al., Nature, 2026-01-10 09:51:42.
Spermatid individualization is a common stage of spermiogenic failure suggesting that a male germline checkpoint may act at this stage during sperm development in Drosophila. However, the molecular identity of such a male germline checkpoint has remained elusive. Here, we show that Overdrive (Ovd), a gene dispensable for male fertility, is required for the selective elimination of post-meiotic spermatids targeted by selfish chromosomes. Gamete elimination occurs during the individualization stage of spermiogenesis, following histone-to-protamine transition failure of targeted spermatids. We show that Ovd is necessary for the selfish behavior of segregation distorters across distantly related Drosophila species, indicating that independent selfish chromosomes use common mechanisms. Our study suggests that the normal function of an Ovd-mediated germline checkpoint involves the elimination of abnormal gametes during male germline development, which is exploited by selfish chromosomes into eliminating competing sperm.
Evolutionary persistence and divergence of the tdk killer meiotic driver family
35476Fan-Yi Zhang, Guo-Song Jia, Jing-Yi Ren, et al., bioRxiv, 2025-12-29 18:22:02.
Killer meiotic drivers (KMDs) are selfish genetic elements that achieve super-Mendelian inheritance by selectively eliminating gametes lacking the driver. Although predicted to arise recurrently, KMDs are generally considered evolutionarily ephemeral—going extinct after fixation or host suppression. The identification of tdk1, a single-gene KMD in the fission yeast Schizosaccharomyces pombe, provides a model for studying KMD evolution. Here, we identify two divergent tdk1 homologs (tdk210 and tdk203) from S. cryophilus, a fission yeast species that diverged ∼100 million years ago from S. pombe, as active KMDs. These three KMDs all act via post-germination killing, disrupting chromosome segregation in noncarrier progeny. Notably, they also exhibit striking functional divergences: tdk1, tdk210, and tdk203 are mutually incompatible (showing no cross-resistance), and the latter two act independently of Bdf1/Bdf2—host chromatin proteins required for tdk1 killing. Phylogenetic analyses of the dozens of tdk family genes in Schizosaccharomyces support long-term persistence and rapid evolutionary dynamics of this gene family. Remarkably, homologs in distantly related fungal phyla display genomic and structural similarities to Schizosaccharomyces tdk genes, suggesting a deeply rooted origin of this KMD family in fungi. Our findings reveal that a single KMD family can undergo repeated functional innovation—generating mutually incompatible variants and rewiring host dependencies—while maintaining a conserved killing mode over deep evolutionary time.
Pervasive suppressors halt the spread of selfish Segregation Distorter in a natural population
35247Ching-Ho Chang, Tyler Handler, Nick Fuda, et al., bioRxiv, 2025-10-16 09:21:01.
Meiotic drivers are selfish genetic elements that subvert Mendelian inheritance to increase their own transmission, yet they are typically found at low frequencies across natural populations. The factors that limit their spread remain unclear. To investigate this paradox, we studied the Segregation Distorter (SD) system, a selfish coadapted gene complex in Drosophila melanogaster. SD biases its transmission by killing sperm carrying a homologous chromosome bearing a target locus, Responder (Rsp), which appear as satellite repeats. Such selfish killing impairs male fertility and imposes selective pressure on the host genome to evolve resistance, either by deleting Rsp copies or acquiring unlinked suppressors. To characterize the spectrum of Rsp alleles and the frequency of segregating suppressors, we surveyed 90 strains from the Drosophila Genome Reference Panel. Rather than loss of Rsp, we found that over half of the strains (52/90) harbor suppressors located on the X chromosome or autosomes, but not the Y chromosome. The widespread presence of strong suppressors limited the resolution of our genome-wide association mapping; however, recombination analysis identified a strong X-linked suppressor to a ~300 kb interval on the chromosome. Together, our findings suggest that pervasive, multilocus suppression constrains the spread of SD in natural populations.
The Stellate meiotic drive system of Drosophila melanogaster is active in contemporary populations
35215Benjamin K McCormick, Daniel A Barbash, Andrew G Clark, bioRxiv, 2025-10-05 12:58:27.
Meiotic drivers are selfish elements that bias their own transmission so that they are overrepresented among the functional gametes produced. The selective costs imposed by drivers on their hosts may trigger intragenomic conflict, promoting the evolution of suppressors and fueling an ongoing arms race between drivers and suppressors. Stellate (Ste) is an X-linked tandemly arrayed multicopy gene. Its copy number ranges from 3 to more than 300 among Drosophila melanogaster strains from the Global Diversity Lines. In wild-type animals, Ste expression is usually suppressed by homologous piRNAs produced from the Suppressor of Stellate (Su(Ste)) array on the Y chromosome. Derepression of Ste in the absence Su(Ste) results in the formation of proteinaceous crystals in spermatocytes, chromatin compaction defects, reductions in fertility, and female-biased sex ratios arising from under-recovery of Y-bearing sperm. Despite extensive study, the function of the Stellate array and evolutionary significance of its persistence in the genome have remained elusive. It has been suggested to be a now-inactive relic of an ancient meiotic drive system, as perturbations in lab stocks can produce Ste-mediated meiotic distortions. Meiotic drive occurring among natural variants, however, has not been reported. We established crosses between females with high Ste copy number X chromosomes and males carrying low Su(Ste) copy number Y chromosomes and found that the male progeny displayed non-Mendelian sex chromosome transmission. Importantly, deletion of the euSte array in an otherwise matched genetic background rescues this phenotype, demonstrating that Stellate is an active driver in contemporary populations.
D. melanogaster meiotic driver Stellate compromises sperm development by impeding nuclear envelope remodeling
35211Xuefeng M Meng, Yukiko M Yamashita, bioRxiv, 2025-10-02 15:00:55.
Meiotic drive is a phenomenon that violates Mendels Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that Lamin Dm0, a component of the nuclear lamina, is rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatid retained Lamin Dm0 for a prolonged time. Delayed Lamin Dm0 removal is associated with defective formation of the dense complex, which is composed of the bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatid led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.
Rapid protamine evolution suppresses meiotic drive in Drosophila
35159Ching-Ho Chang, Aida Flor de la Cruz, Isabel Mejia Natividad, Alex Noyola, Harmit S. Malik, bioRxiv, 2025-09-22 10:55:08.
Many animal species replace histones with protamines during spermatogenesis. Despite their importance for sperm function, protamines rapidly evolve in many species; the biological causes behind their rapid evolution remain unknown. Here, using in vivo gene replacement, we investigated the causes and consequences underlying the rapid evolution of protamine Mst77F, which is essential for male fertility in D. melanogaster. Mst77F ortholog replacements led to defects in DNA compaction of X-chromosome-bearing sperm compared to Y-chromosome-bearing sperm during spermatogenesis, resulting in fewer X-bearing mature sperm and male-biased progeny. Unlike D. melanogaster, Mst77F is not essential for male fertility in D. yakuba but is still required to suppress sex-ratio distortion. Our results suggest that relentless pressure to suppress sex chromosomal meiotic drive drives the rapid evolution of protamines.
Single-cell consequences of X-linked meiotic drive in stalk-eyed flies
35155Price PD, Parkus SM, Lloyd VJ, Alston BT, Bradshaw SL, Bates S, et al., PLoS Genet, 21. 2025-09-22 10:33:47.
Meiotic drivers, a class of selfish gene, are frequently located on sex chromosomes and have dramatic impacts on gamete development. However, our understanding of their molecular consequences for gamete production and sex chromosome regulation has focused on a handful of model organisms. In this study, we use single-cell RNA-sequencing approaches to produce a single-cell atlas of the testis of the stalk-eyed fly, Teleopsis dalmanni. This species harbours an X-linked meiotic driver where drive males produce more than 90% female offspring. First, we generate a comprehensive profile of the cellular and transcriptional landscape of spermatogenesis. We show limited evidence for meiotic sex chromosome inactivation and unique patterns of dosage compensation across spermatogenesis, relative to both other dipterans and insects in general. Finally, by comparing single-cell expression data between standard and drive males, we show that although there are significant differences in genome regulation, broad expression dynamics in the testis are conserved in the presence of meiotic drive. Notably, we highlight key genes with perturbed expression as a potential consequence of the disruption of spermatogenesis by the X-linked meiotic driver.
Autosomally-encoded segregation distortion of sex chromosomes
35096Greenberg Naomi L., Patten Manus M. and Schenkel Martijn A., Proc. R. Soc. B., 292. 2025-09-01 19:48:42.
Some selfish genetic elements drive at meiosis to achieve transmission distortion, breaking the rules of Mendelian segregation to enhance their own evolutionary success. It has been shown that enhancers of drive must act in cis in order to gain the selfish benefit of drive and that suppressors of drive will be selected at unlinked loci. Here, we model the evolution of an autosomal trans-acting gene (Distorter) that causes the Y chromosome (or even 0 chromosome) to drive without driving itself, a phenomenon we call ‘remote-control meiotic drive’. We show that such a gene may spread in the population when linked to a second locus, Assister, whose alleles are transmitted at different frequencies through sperm as compared to eggs, for which we consider various scenarios, such as sexually antagonistic selection or sex-limited drive. Depending on the mechanistic details of sex-chromosome drive, Distorter’s spread can additionally facilitate transitions between XY and X0 sex determination. Our results provide a proof of principle that stretches the current understanding of segregation modifier and sex allocation theory. Moreover, we identify alternative evolutionary trajectories that could also lead to remote control drive and discuss its potential applications in developing synthetic sex-ratio-distorting elements for use in pest management, for example.
Spindle checkpoint can secure additional cheating time for selfish expanded centromeres
35092Walton, R. Zaak et al., Current Biology, 35:3687-3696. 2025-09-01 19:39:54.
Expanded centromeric satellite repeats can violate Mendel’s law of segregation by preferentially segregating to the egg. In mice, these selfish centromeres enrich microtubule destabilizers at pericentromeres to detach from the spindle and flip toward the egg side of the meiotic spindle, thereby achieving preferential segregation. However, despite the consistent enrichment of destabilizers upon centromere expansion, such enrichment alone is insufficient to drive the preferential retention of expanded centromeres, suggesting a missing component in understanding their non-Mendelian segregation. Here, we propose that prolonged spindle checkpoint activation is crucial for expanded centromeres to cheat the segregation process by providing sufficient time for them to flip toward the egg side. By experimentally manipulating kinetochore size in a species-specific manner, we found that assembling larger kinetochores triggers robust spindle checkpoint activation, leading to anaphase delay and preferential retention of expanded centromeres in the egg. Comparisons across multiple hybrid mouse models revealed that centromeric satellite asymmetry does not consistently lead to kinetochore asymmetry and anaphase delay, explaining why satellite asymmetry does not always result in the preferential retention of larger centromeres. Altogether, this work highlights the significance of checkpoint activation in exploiting the inherent asymmetry in female meiosis and the distinct responses of kinetochore proteins and microtubule destabilizers to centromere expansion.
Novel stressors and trait variation determine X-linked meiotic drive frequency
35021Fisher Adam M., White Nicola, Bonsall Michael B., Price Tom AR. and Knell Robert J., Proc. R. Soc. B., 292. 2025-08-13 16:09:01.
Sex ratio meiotic drive alleles bias their transmission by impairing the viability of non-drive gametes, leading to skewed population sex ratios. Despite theoretical predictions that drive alleles should reach fixation causing population extinction, meiotic drive persists at intermediate frequencies in wild populations, though the reasons for this are unclear. Here, we investigate how novel environmental stress and genotype-specific fitness costs contribute to drive frequency. Using a suppression-free X-linked meiotic drive system in Drosophila pseudoobscura, we exposed flies to varying doses of the pesticide permethrin and measured mortality and fecundity across genotypes. We found that drive-bearing males (SR) and drive-homozygous females (SRSR) exhibited heightened mortality, both in the presence and absence of pesticide, while heterozygous (SRST) females exhibited superior fecundity. Using a mathematical model parametrized with our empirical findings, we explored the long-term population dynamics of meiotic drive under different conditions. Our model predicts that drive frequency has a concave relationship with pesticide dose and is strongly modulated by genotype-specific female fecundity. These results suggest that novel environmental stressors and drive-induced fitness effects play key roles in determining meiotic drive frequencies. Our findings improve our understanding of drive frequencies in the wild and have direct implications for drive-based pest control.
Drive, suppression, and escape from suppression of a selfish chromosome
35016Jackson Taylor Ridges, Jackson Bladen, Robert L. Unckless, Nitin Phadnis, bioRxiv, 2025-08-11 14:46:50.
Meiotic drivers are selfish chromosomes that are predicted to spark a rapid intragenomic arms-race 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 reconstruct the evolutionary history of this SR chromosome and show that its genetic architecture and complexity has been shaped by a history of drive, suppression, and escape from suppression. Our results indicate that the current lack of resistance to the SR chromosome represents a transient condition awaiting the emergence of new suppressors.
Suppression of sex-ratio drive in Drosophila subobscura
35233Sophie Lyth, Tom Gill, Andri Manser, et al., Evolution, 2025-07-30 15:46:21.
Selfish genetic elements enjoy an evolutionary advantage by enhancing their own transmission to offspring, and their genetic suppressors are favored when they re-establish fair inheritance patterns. Here, we study an X-linked sex ratio drive system (SR) in Drosophila subobscura, which kills Y-bearing sperm of SR males, resulting in the over-transmission of the SR chromosome and a strong female bias in their offspring. We surveyed D. subobscura populations in North Africa, which naturally harbor SR, and found that suppression occurs in ∼13.5% of wild-derived lines. We characterize this suppression phenotype through a series of crossing experiments, including multigenerational introgression of SR chromosomes into a suppressing genetic background. We show that introgression can restore normal offspring sex ratios or, in some cases, result in an excess of male offspring. This suppression appears to be a multilocus trait, involving autosomes and the Y chromosomes. Suppression of SR fails to ameliorate all costs of drive, with fully suppressed SR-carrying males having depressed fertility and low offspring egg hatch rates. Further examination of internal male reproductive organs using microscopy suggests that suppressed SR males also have abnormal testes. These factors may explain why the suppression fails to reach high frequencies, despite the strong advantage of suppressing SR.
The B Chromosome of Pseudococcus viburni: A Selfish Chromosome that Exploits Whole-Genome Meiotic Drive
34939Isabelle M Vea, Andrés G de la Filia, Kamil S Jaron, Scott E J Barlow, Marion Herbette, Andrew J Mongue, Ross Nelson, Francisco J Ruiz-Ruano, Laura Ross, Genome Biology and Evolution, 17. 2025-06-24 08:56:02.
Meiosis is generally a fair process: each chromosome has a 50% chance of being included into each gamete. However, meiosis can become aberrant with some chromosomes having a higher chance of making it into gametes than others. Yet, why and how such systems evolve remains unclear. Here, we study the unusual reproductive genetics of mealybugs, where only maternal-origin chromosomes are included in gametes during male meiosis, while paternal chromosomes are eliminated. One species—Pseudococcus viburni—has a segregating B chromosome that drives by escaping paternal genome elimination. We present whole genome and gene expression data from lines with and without B chromosomes. We identify B-linked sequences including 204 protein-coding genes and a satellite repeat that makes up a significant proportion of the chromosome. The few paralogs between the B and the core genome are distributed throughout the genome, arguing against a simple, or at least recent, chromosomal duplication of one of the autosomes to create the B. We do, however, find one 373 kb region containing 146 genes that appears to be a recent translocation. Finally, we show that while many B-linked genes are expressed during meiosis, most of these are encoded on the recently translocated region. Only a small number of B-exclusive genes are expressed during meiosis. Of these, only one was overexpressed during male meiosis, which is when the drive occurs: an acetyltransferase involved in H3K56Ac, which has a putative role in meiosis and is, therefore, a promising candidate for further studies.
Conflicting Kinesin-14s in a single chromosomal drive haplotype
34899Meghan J Brady, Anjali Gupta, Jonathan I Gent, et al., Genetics, 2025-06-06 08:37:38.
In maize, there are 2 meiotic drive systems that target large heterochromatic knobs composed of tandem repeats known as knob180 and TR-1. The first meiotic drive haplotype, abnormal chromosome 10 (Ab10) confers strong meiotic drive (∼75% transmission as a heterozygote) and encodes 2 kinesins: KINDR, which associates with knob180 repeats, and TRKIN, which associates with TR-1 repeats. Prior data show that meiotic drive is conferred primarily by the KINDR/knob180 system while the TRKIN/TR-1 system seems to have little or no role, making it unclear why Trkin has been maintained in Ab10 haplotypes. The second meiotic drive haplotype, K10L2, confers a low level of meiotic drive (∼51–52%) and only encodes the TRKIN/TR-1 system. Here, we used long-read sequencing to assemble the K10L2 haplotype and showed that it has strong homology to an internal portion of the Ab10 haplotype. We also carried out CRISPR mutagenesis to test the role of Trkin on Ab10 and K10L2. The data indicate that the Trkin gene on Ab10 does not improve drive or fitness but instead has a weak deleterious effect when paired with a normal chromosome 10. The deleterious effect is more severe when Ab10 is paired with K10L2: in this context, functional Trkin on either chromosome nearly abolishes Ab10 drive. Mathematical modeling based on the empirical data suggests that Trkin is unlikely to persist on Ab10. We conclude that Trkin either confers an advantage to Ab10 in untested circumstances or that it is in the process of being purged from the Ab10 population.
Intrinsically weak sex chromosome drive through sequential asymmetric meiosis
34889Xuefeng Meng, Yukiko M. Yamashita, Science Advances, 11. 2025-06-02 19:06:59.
Meiotic drivers are selfish genetic elements that bias their own transmission, violating Mendel’s Law of Equal Segregation. It has long been recognized that sex chromosome–linked drivers present a paradox: Their success in transmission can severely distort populations’ sex ratio and lead to extinction. This paradox is typically solved by the presence of suppressors or fitness costs associated with the driver, limiting the propagation of the driver. Here, we show that Stellate (Ste) in Drosophila melanogaster represents a novel class of X chromosome–linked driver that operates with an inherent mechanism that weakens its drive strength. Ste protein asymmetrically segregates into Y-bearing cells during meiosis I, subsequently causing their death. Unexpectedly, Ste segregates asymmetrically again during meiosis II, sparing half of the Y-bearing spermatids from Ste-induced defects, thereby weakening the drive strength. Our findings reveal a mechanism by which sex chromosome drivers avoid suicidal success.
A male-transmitted B chromosome undergoes strong meiotic drag in females
34850Patrick M Ferree, Jayla Cummings, Emma Garman, et al, bioRxiv, 2025-05-26 20:12:34.
Many organisms carry extra, non-essential chromosomes known as B chromosomes (Bs), which are selfishly transmitted at super-Mendelian levels to offspring. This heightened transmission, termed drive, occurs during gametogenesis, usually in one of the two parents. In some cases, Bs can experience an opposing process, drag, which reduces their transmission. If these processes occur together in the same organism, one in each parental sex, then they may facilitate the spread of Bs while countering their accumulation in the genome to harmful levels. While previous studies have elucidated mechanistic aspects of B drive, little is known about drag or other factors that govern the inheritance of these selfish genetic elements. Here we examined the inheritance of Paternal Sex Ratio (PSR), a single-copy B in the jewel wasp, Nasonia vitripennis, which is transmitted paternally to offspring. PSR drives by converting female-destined embryos into PSR-transmitting males. Using genetic manipulation, we produced exceptional PSR-carrying females, which were used to assess B transmission potential. We found that females transmit PSR at unexpectedly low levels compared to univalent chromosomes in other organisms. This reduced transmission stems from remarkable loss of PSR from the egg's nucleus upon entry into meiosis, an effect that may be caused by an absence of microtubule-based spindle fibers in meiosis I-arrested wasp eggs. We also found that PSR is strictly limited to a single copy per genome, suggesting that two PSR copies are lethal during development. Our findings reveal the successful inheritance of this selfish B chromosome involves a restriction to a single copy and hidden female meiotic drag in addition to its strong paternal drive.
A selfish supergene causes meiotic drive through both sexes in Drosophila
34805G.L. Keais,C.M. Saad-Roy,E. Gonzalez-Sqalli, et al., Proceedings of the National Academy of Sciences, 122. 2025-04-25 12:15:11.
Meiotic drivers are selfish genetic elements that bias their own transmission during meiosis or gamete formation. Due to the fundamental differences between male and female meiosis in animals and plants, meiotic drivers operate through distinct mechanisms in the two sexes: In females, they exploit the asymmetry of meiosis to ensure their inclusion in the egg, whereas in males, they eliminate competing gametes after symmetric meiosis. Meiotic drive is commonly reported in males, where it strongly influences the evolution of spermatogenesis, while the few known cases in females have highlighted its crucial role in centromere evolution. Despite a growing number of examples in a wide range of organisms, meiotic drive has so far only been observed in one sex or the other since its discovery nearly 100 y ago. Here, we show that a selfish X chromosome known to cause meiotic drive in male Drosophila testacea flies also causes meiotic drive in females. We find that this X chromosome has supergene architecture, harboring extensive structural rearrangements that suppress recombination between the two X chromosomes. This has contributed to a substantial expansion of its size compared to the wild-type chromosome, partly due to the accumulation of species-specific repetitive elements. Our findings suggest that female meiotic drive may play an important role in the evolutionary dynamics of polymorphic structural variants that suppress recombination, including inversions, translocations, and supergenes.
An innovation in host responses to escalating genomic conflicts
34753Martí, Emiliano et al., Trends in Genetics, 2025-04-07 12:54:24.
Conflicts between selfish elements and their hosts can trigger rapid structural and regulatory changes in genomes. Chen et al. discovered a novel species-specific innovation in response to a meiotic driver in Drosophila melanogaster. Their discovery highlights a new dimension in adaptive responses to selfish elements, with broad evolutionary consequences.
Functional constraints of wtf killer meiotic drivers
34646Nidamangala Srinivasa A., Campbell S., Venkatesan S., et al., PLOS Genetics, 21. 2025-03-21 14:59:22.
Diploid organisms, such as humans, have two copies of most genes. Only one copy, however, is transmitted through gametes (e.g., sperm and egg) to any given offspring. Alternate copies of the same gene are expected to be equally represented in the gametes, resulting in random transmission to the next generation. However, some genes can “cheat” to be transmitted to more than half of the gametes, often at a cost to the host organism. Killer meiotic drivers are one such class of cheater genes that act by eliminating gametes lacking the driver. In this work, we studied the wtf family of killer meiotic drivers found in fission yeasts. Each wtf driver encodes a poison and an antidote protein to specifically kill gametes that do not inherit the driver. Through analyzing a large suite of diverse natural and engineered mutant wtf genes, we identified multiple properties—such as poison self-assembly and poison-antidote co-assembly—that can constrain poison toxicity and antidote rescue. These constraints could influence the evolution of wtf genes. Additionally, we discovered several incompatible wtf poison-antidote pairs, demonstrating expanded potential for self-killing wtf alleles. Such alleles could potentially arise spontaneously in populations cause infertility.
Stowers scientists uncover principles underlying the toxicity of “selfish” genes
34644Stowers Institute for Medical Research, PRNewswire, 2025-03-21 14:55:28.
Lurking within the genomes of nearly all species—including plants, fungi, and even humans—are genes that are passed from generation to generation with no clear benefit to the organism. Called "selfish" genes, they can sometimes be harmful or even lethal. A recent study from the Stowers Institute for Medical Research sheds new light on how selfish genes "cheat" inheritance to ensure they are passed to the next generation, often at the expense of an organism's fertility. The collaboration between the labs of Associate Investigators SaraH Zanders, Ph.D., and Randal Halfmann, Ph.D., investigated these selfish genes in fission yeast, a single-celled organism and powerful system for genetic research. The teams uncovered common principles in how the widely variable wtf selfish gene family harms cells, and these properties likely exist across many forms of life. Published in PLoS Genetics on [date], the findings reveal that the ability of these selfish genes to rapidly evolve contributes to their long-term evolutionary success yet can also occasionally lead to their own self-destruction. Selfish genes operate by "driving" or favoring their own transmission during reproduction. The most extreme class, called killer meiotic drivers, create toxic proteins that destroy reproductive cells—except for those that inherit the gene that are saved by also making a protein "antidote."
Antagonistic kinesin-14s within a single chromosomal drive haplotype
34531Meghan J. Brady, Anjali Gupta, Jonathan I. Gent, et al., bioRxiv, 2025-02-21 10:31:41.
In maize, there are two meiotic drive systems that operate on large tandem repeat arrays called knobs that are found on chromosome arms. One meiotic drive haplotype, Abnormal chromosome 10 (Ab10), encodes two kinesin proteins that interact with two distinct tandem repeat arrays in a sequence-specific manner to confer meiotic drive. The kinesin KINDR associates with knob180 repeats while the kinesin TRKIN associates with TR-1 repeats. Prior data show that meiotic drive is conferred primarily by the KINDR/knob180 system, with the TRKIN/TR-1 system having little or no role. The second meiotic drive haplotype, K10L2, shows low levels of meiotic drive and only encodes the TRKIN/TR-1 system. Here we used long-read sequencing to assemble the K10L2 haplotype and showed that it has strong homology to an internal portion of the Ab10 haplotype. We also carried out CRISPR mutagenesis of Trkin to test the role of Trkin on Ab10 and K10L2. The data indicate that the Trkin gene on Ab10 does not improve drive or fitness but instead has a weak deleterious effect when paired with a normal chromosome 10. The deleterious effect is more severe when Ab10 is paired with K10L2: in this context functional Trkin on either chromosome nearly abolishes Ab10 drive. We modeled the effect of Trkin on Ab10 and found it should not persist in the population. We conclude that Trkin either confers an advantage to Ab10 in untested circumstances or that it is in the process of being purged from the Ab10 population.
Functional constraints of wtf killer meiotic drivers
34527Nidamangala Srinivasa A, Campbell S, Venkatesan S, et al., PLOS Genetics, 21. 2025-02-21 09:42:22.
Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver− heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver− gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.
Selfish Genetic Elements and Meiotic Drive in Drosophila
34367Nature Research Intelligence, 2025-01-28 14:04:45.
Selfish genetic elements are segments of DNA that can enhance their own transmission to the next generation, often at a cost to the organism's overall fitness. In Drosophila, or fruit flies, these elements can lead to a phenomenon known as meiotic drive, where certain alleles are preferentially passed on during reproduction, violating Mendel's law of equal segregation. Recent research has focused on understanding the mechanisms behind these selfish elements, their evolutionary implications, and how they can affect the fitness and reproductive success of their hosts.
Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana
34259Ricou, A., Simon, M., Duflos, R., et al, PLOS Genetics, 21. 2025-01-14 09:53:12.
Gamete killers are genetic loci that distort segregation in the progeny of hybrids because the killer allele promotes the elimination of the gametes that carry the sensitive allele. They are widely distributed in eukaryotes and are important for understanding genome evolution and speciation. We had previously identified a pollen killer in hybrids between two distant natural accessions of Arabidopsis thaliana. This pollen killer involves three genetically linked genes, and we previously reported the identification of the gene encoding the antidote that protects pollen grains from the killer activity. In this study, we identified the two other genes of the pollen killer by using CRISPR-Cas9 induced mutants. These two genes are necessary for the killer activity that we demonstrated to be specific to pollen. The cellular localization of the pollen killer encoded proteins suggests that the pollen killer activity involves the mitochondria. Sequence analyses reveal predicted domains from the same families in the killer proteins. In addition, the C-terminal half of one of the killer proteins is identical to the antidote, and one amino acid, crucial for the antidote activity, is also essential for the killer function. Investigating more than 700 worldwide accessions of A. thaliana, we confirmed that the locus is subject to important structural rearrangements and copy number variation. By exploiting available de novo genomic sequences, we propose a scenario for the emergence of this pollen killer in A. thaliana. Furthermore, we report the co-occurrence and behavior of killer and sensitive genotypes in several local populations, a prerequisite for studying gamete killer evolution in the wild. This highlights the potential of the Arabidopsis model not only for functional studies of gamete killers but also for investigating their evolutionary trajectories at complementary geographical scales.
Escalation of genome defense capacity enables control of an expanding meiotic driver
34251P. Chen, K.C. Pan, E.H. Park, et al., Proceedings of the National Academy of Sciences, 122. 2025-01-13 15:02:27.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via innovation of specificity factors. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to specificity factor innovations, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the genome defense capacity to control a recently expanded selfish gene in Drosophila melanogaster. Through a targeted RNAi screen for repressors of Stellate—a recently evolved meiotic driver—we identified a defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to elevate Aub and AGO3 expression, thereby escalating the silencing capacity of piRNA pathway to tame expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life, we envision that augmenting the defense capacity to quantitatively match selfish genes is a repeatedly employed defense strategy in evolution.
Biased social chromosome transmission in males of the fire ant Solenopsis invicta
34049Daniel R Hettesheimer, Haolin Zeng, Brendan G Hunt, Kenneth G Ross, G3: Genes|Genomes|Genetics, 2024-12-16 14:21:28.
Selfish genetic elements subvert the normal rules of inheritance to unfairly propagate themselves, often at the expense of other genomic elements and the fitness of individuals carrying them. Social life provides diverse avenues for the propagation of such elements. In the fire ant Solenopsis invicta, polymorphic social organization is controlled by a social chromosome, one variant of which (Sb) enhances its own transmission in polygyne colonies through effects on caste development and queen acceptance by workers. Whether the selfish effects of Sb extend to haploid (reproductive) males in this system is less clear. Here, we demonstrate a strong overrepresentation of the Sb social chromosome haplotype in reproductive males, relative to Mendelian expectations, in both the pupal and adult stages. We tested for the presence of selective execution of adult SB males by workers but did not detect such behavior. Combined with the presence of a strong imbalance in the haplotype frequencies already early in the pupal stage, these results indicate that the Sb supergene may distort male haplotype frequencies during larval or embryonic development. These findings are significant because they demonstrate yet another mode by which the selfish tendencies of the Sb supergene are manifested, illuminate complex interactions between Sb and the fire ant breeding system, inform the development of models of the population dynamics of Sb, and illustrate how a selfish supergene can increase in frequency in a population despite harboring deleterious mutations.
A meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring
33620Yu Hua, Jianxiu Zhang, et al., PNAS, 121. 2024-11-12 14:39:25.
Killer meiotic drivers (KMDs) are selfish genetic elements that distort Mendelian inheritance by selectively killing meiotic products lacking the KMD element, thereby promoting their own propagation. Although KMDs have been found in diverse eukaryotes, only a limited number of them have been characterized at the molecular level, and their killing mechanisms remain largely unknown. In this study, we identify that a gene previously deemed essential for cell survival in the fission yeast Schizosaccharomyces pombe is a single-gene KMD. This gene, tdk1, kills nearly all tdk1Δ progeny in a tdk1+ × tdk1Δ cross. By analyzing polymorphisms of tdk1 among natural strains, we identify a resistant haplotype, HT3. This haplotype lacks killing ability yet confers resistance to killing by the wild-type tdk1. Proximity labeling experiments reveal an interaction between Tdk1, the protein product of tdk1, and the epigenetic reader Bdf1. Interestingly, the nonkilling Tdk1-HT3 variant does not interact with Bdf1. Cryoelectron microscopy further elucidated the binding interface between Tdk1 and Bdf1, pinpointing mutations within Tdk1-HT3 that disrupt this interface. During sexual reproduction, Tdk1 forms stable Bdf1-binding nuclear foci in all spores after meiosis. These foci persist in germinated tdk1Δ progeny and impede chromosome segregation during mitosis by generating aberrant chromosomal adhesions. This study identifies a KMD that masquerades as an essential gene and reveals the molecular mechanism by which this KMD hijacks cellular machinery to execute killing. Additionally, we unveil that losing the hijacking ability is an evolutionary path for this single-gene KMD to evolve into a nonkilling resistant haplotype.
Genetic study solves the mystery of ‘selfish’ B chromosomes in rye
33606Leibniz Institute of Plant Genetics and Crop Plant Research, Phys.org, 2024-11-12 09:04:08.
Some chromosomes, such as B chromosomes, can increase their inheritance rate to their own advantage. These extra chromosomes are found in many plants, animals, and fungi and rely upon various strategies to avoid being eliminated over time, as most organisms tend to remove non-essential genetic elements. However, the genetic mechanisms by which B chromosomes avoid elimination are poorly understood. An international research team led by IPK Leibniz Institute identified genes on the rye B chromosome that are likely responsible for regulating this process. The results were published in Nature Communications. Supernumerary B chromosomes, unlike A (standard) chromosomes, are not required for the normal growth and development of organisms and as of 2024, B chromosomes have been discovered in almost 3,000 species from all eukaryotic phyla. Most B chromosomes confer no detectable selective consequences at low numbers, but increased numbers can result in phenotypic aberrations and reduced fertility. To avoid elimination, many B chromosomes influence cell division in their favor and increase their copy number in the process. This phenomenon is called chromosome drive. The "selfish" B chromosomes, therefore, only become active when their existence is at stake and not for the benefit of the plant.
Engineering Resilient Gene Drives Towards Sustainable Malaria Control: Predicting, Testing and Overcoming Target Site Resistance
33379Ioanna Morianou, Lee Phillimore, Bhavin S. Khatri,, bioRxiv, 2024-11-04 13:56:24.
CRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance. Here, we present a pipeline for the accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our method to stress-test a highly effective gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, and discovered novel, partially resistant alleles that can perturb drive-invasion dynamics. We then engineered next-generation gene drives that can actively remove resistant alleles by targeting several highly conserved and non-overlapping sites in the female-specific exon of the doublesex gene. Our models predict that such gene drive designs could suppress large, natural populations of the malaria mosquito in the field.
Using genomics to find solutions to malaria
32714Morgan Morris, Nature Africa, 2024-10-22 17:47:10.
Joel Odero’s experiences of malaria is wide and deep. Growing up in a village in Kenya, he not only contracted the disease numerous times, but was all too familiar with the relentless daily regimen of spraying insecticides and checking malaria nets were not ripped. Decades later, as a research scientist with the Ifakara Health Institute in Tanzania, he witnessed firsthand how, for many, that daily grind is still ongoing. As part of the institute’s teams that, between 2018 and 2022, spread out across the country to capture a range of malaria-transmitting mosquitoes for studying, he would collect samples from homes where people had to spray and check their nets every day. Odero is part of a generation of scientists trying to break the stranglehold of the Anopheles mosquitoes that transmit the disease-causing parasite. Their weapon of choice is genomics. It’s a challenge taken up by organizations like Target Malaria, a not-for-profit international research consortium featuring teams in Africa, the US and Europe, and funded by, among others, the Bill & Melinda Gates Foundation and Open Philanthropy. There, researchers’ game plan is simple: reduce the population numbers of the mosquitoes, specifically those of three related species responsible for most malaria transmissions in Africa – Anopheles gambiae, Anopheles coluzzii and Anopheles arabiensis. To do so, they are looking to capitalize on a naturally occurring phenomenon, gene drive. Often described as “selfish genetic elements”, taking the form of bits of DNA code, genes are ‘driven’ when a gene that has a favorable effect becomes more prevalent in successive generations. Typically, with both humans and mosquitoes, offspring inherit two copies of any gene, one from each parent. As a result, there is a 50/50 chance of either of the two copies being passed on to later generations. Using gene drives, researchers are manipulating the bias that is introduced to that rate of inheritance so that a specific trait is nearly 100% guaranteed to be passed on. Gene-drive malaria research takes on many forms. Two of the most popular are known as ‘population replacement’ and ‘population suppression’. With population replacement, the aim is to modify the mosquitoes so that they are no longer vectors, aka transmitters, of the malaria parasite. With population suppression – which the work of Target Malaria falls under – the goal is to reduce the mosquito population. Target Malaria’s strategy is to sterilise and reduce the number of female mosquitoes. The females transmit the malaria-causing parasite known as Plasmodium falciparum to humans, and whose numbers typically determine the size of a mosquito population. The gene drive approach would be a game changer, says Target Malaria’s Abdoulaye Diabaté, head of medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences in Bobo-Dioulasso. “It’s clear that the tools that we have today are not the ones that can take us to malaria elimination,” says Diabaté. It is the failure of these ageing tools, or the fear that they might fail, that is driving the gene-based approach to malaria research in Africa and elsewhere.
Stalk-eyed flies carrying a driving X chromosome compensate by increasing fight intensity
32712Kimberly A. Paczolt, Macy E. Pritchard, Gabrielle T. Welsh, et al., Frontiers in Ethology, 3. 2024-10-22 17:39:40.
Exaggerated ornaments provide opportunities to understand how selection can operate at different levels to shape the evolution of a trait. While these features aid their bearer in attracting mates or fending off competitors, they can also be costly and influenced by the environment and genetic variation. The eyestalks of the stalk-eyed fly, Teleopsis dalmanni, are of interest because eyestalk length is the target of both intra- and intersexual selection and is also reduced by loci on a highly-divergent sex ratio X chromosome (XSR), a meiotic driver accounting for up to 30% of wild X chromosomes. Male stalk-eyed flies fight to control access to females and over food using a combination of low-intensity displays and high-intensity physical fights. We staged, filmed, and scored contests between pairs of eyespan-matched males to evaluate whether X chromosome type impacts the behavior and outcome of aggressive interactions. While our results broadly match expectations from previous studies, we found that XSR males used more high-intensity behaviors than males carrying a non-driving, standard X chromosome (XST), particularly when their eyestalks were of similar size or smaller than their opponents. Additionally, we found that when XSR males use high-intensity behaviors, they win more bouts than when they use low-intensity behaviors. Taken together, these results suggest that XSR impacts male aggressive behavior to compensate for the shorter eyestalks of XSR males and may help to explain how this selfish chromosome is maintained.
Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana
32527Anthony Ricou, Matthieu Simon, et al., bioRxiv, 2024-10-15 11:51:17.
Certain genetic elements are qualified as selfish because they favor their transmission to the progeny during reproduction to the detriment of gametes that do not carry them. These elements are widespread in fungi as well as in plants or in animals, and they are made up of two or even three components, which are specific to each species. Therefore, they must be studied on a case-by-case basis. Moreover, understanding how they appear and propagate in local population remains a major issue in evolutionary biology. Here we have characterized, in the model plant Arabidopsis, the three genes involved in such an element, called a pollen killer. This pollen killer targets the mitochondria to cause the death of pollen grains that do not carry it. We investigated the three genes in several hundred genotypes collected worldwide, giving us a global view of their diversity at the species level. We also found that some French local populations contain both sensitive and killer plants, which constitutes an invaluable resource for studying the evolution of a pollen killer in the wild.
Evolutionary modes of wtf meiotic driver genes in Schizosaccharomyces pombe
32524Yan-Hui Xu, Fang Suo, Xiao-Ran Zhang, et al., Genome Biology and Evolution, 2024-10-15 11:46:16.
Killer meiotic drivers (KMDs) are a class of selfish genetic elements that bias inheritance in their favor by destroying meiotic progeny that do not carry them. How KMDs evolve is not well understood. In the fission yeast Schizosaccharomyces pombe, the largest gene family, known as the wtf genes, is a KMD family that causes intraspecific hybrid sterility. Here, we investigate how wtf genes evolve using long-read-based genome assemblies of 31 distinct S. pombe natural isolates, which encompass the known genetic diversity of S. pombe. Our analysis, involving nearly 1,000 wtf genes in these isolates, yields a comprehensive portrayal of the intraspecific diversity of wtf genes. Leveraging single-nucleotide polymorphisms in adjacent unique sequences, we pinpoint wtf-gene-containing loci that have recently undergone gene conversion events and infer their pre-gene-conversion state. These events include the revival of wtf pseudogenes, lending support to the notion that gene conversion plays a role in preserving this gene family from extinction. Moreover, our investigation reveals that solo long terminal repeats (LTRs) of retrotransposons, frequently found near wtf genes, can act as recombination arms, influencing the upstream regulatory sequences of wtf genes. Additionally, our exploration of the outer boundaries of wtf genes uncovers a previously unrecognized type of directly oriented repeats flanking wtf genes. These repeats may have facilitated the early expansion of the wtf gene family in S. pombe. Our findings enhance the understanding of the mechanisms influencing the evolution of this KMD gene family.
The ultra-selfish gene
31608Mathias Kirk Bonde, Works in Progress, 2024-09-18 20:59:37.
Almost every cell in our bodies contains 23 pairs of chromosomes, which are packages of the DNA and genes that provide the code for producing living things. Sperm and egg cells, however, each contain only one set of chromosomes. This set of chromosomes has been recombined from their parents’ chromosomes, meaning it contains a random mixture of segments from the parents. When a sperm and egg cell fuse, the resulting cell has a pair of each chromosome once again, resulting in 23 pairs. Because the sections of each chromosome to be passed on were selected randomly, any specific gene in a parent has only a 50 percent chance of making it to the next generation. A gene that helps organisms to have more surviving offspring will gradually become more widespread in the population. But some genes have found ways of overriding this process. For example, what if a gene makes the sperm or egg more likely to inherit the section of DNA where the gene itself is located? In that case, the selection process is no longer random, and the gene can spread across the population even if the gene carries no advantage to the animal’s fitness.
Autosomal suppression of sex-ratio meiotic drive influences the dynamics of X and Y chromosome coevolution
31322Anjali Gupta, Robert L Unckless, Journal of Heredity, 2024-09-03 15:54:00.
Sex-ratio meiotic drivers are selfish genes or gene complexes that bias the transmission of sex chromosomes resulting in skewed sex ratios. Existing theoretical models have suggested the maintenance of a four-chromosome equilibrium (with driving and standard X and suppressing and susceptible Y) in a cyclic dynamic, studies of natural populations have failed to capture this pattern. Although there are several plausible explanations for this lack of cycling, interference from autosomal suppressors has not been studied using a theoretical population genetic framework even though autosomal suppressors and Y-linked suppressors coexist in natural populations of some species. In this study, we use a simulation-based approach to investigate the influence of autosomal suppressors on the cycling of sex chromosomes. Our findings demonstrate that the presence of an autosomal suppressor can hinder the invasion of a Y-linked suppressor under some parameter space, thereby impeding the cyclic dynamics, or even the invasion of Y-linked suppression. Even when a Y-linked suppressor invades, the presence of an autosomal suppressor can prevent cycling. Our study demonstrates the potential role of autosomal suppressors in preventing sex chromosome cycling and provides insights into the conditions and consequences of maintaining both Y-linked and autosomal suppressors.
Functional and evolutionary constraints of wtf killer meiotic drivers
31213Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders, bioRxiv, 2024-08-29 10:38:59.
Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver- heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver- gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.
An egg-sabotaging mechanism drives non-Mendelian transmission in mice
31028Frances E. Clark, Naomi L. Greenberg, Duilio M.Z.A. Silva, et al, Current Biology, 2024-08-05 11:40:23.
Selfish genetic elements drive in meiosis to distort their transmission ratio and increase their representation in gametes, violating Mendel’s law of segregation. The two established paradigms for meiotic drive, gamete killing and biased segregation, are fundamentally different. In gamete killing, typically observed with male meiosis, selfish elements sabotage gametes that do not contain them. By contrast, killing is predetermined in female meiosis, and selfish elements bias their segregation to the single surviving gamete (i.e., the egg in animal meiosis). Here, we show that a selfish element on mouse chromosome 2, Responder to drive 2 (R2d2), drives using a hybrid mechanism in female meiosis, incorporating elements of both killing and biased segregation. We propose that if R2d2 is destined for the polar body, it manipulates segregation to sabotage the egg by causing aneuploidy, which is subsequently lethal in the embryo, ensuring that surviving progeny preferentially contain R2d2. In heterozygous females, R2d2 orients randomly on the metaphase spindle but lags during anaphase and preferentially remains in the egg, regardless of its initial orientation. Thus, the egg genotype is either euploid with R2d2 or aneuploid with both homologs of chromosome 2, with only the former generating viable embryos. Consistent with this model, R2d2 heterozygous females produce eggs with increased aneuploidy for chromosome 2, increased embryonic lethality, and increased transmission of R2d2. In contrast to typical gamete killing of sisters produced as daughter cells in a single meiosis, R2d2 prevents production of any viable gametes from meiotic divisions in which it should have been excluded from the egg.
Male-killing virus leads to more female moths
28365Anonymous, Nature, 2023-11-07 09:51:08.
Keisuke Nagamine at Minami Kyushu University in Miyazaki, Japan, and his colleagues have identified another virus that kills male embryos of the tobacco caterpillar, Spodoptera litura. Female moths infected with the virus produced an equal number of male and female embryos, but almost no male embryos survived. The virus doesn’t share male-killing genes with other known male-killing viruses or bacteria, suggesting that these mechanisms evolved independently.
Male-killing virus in a noctuid moth Spodoptera litura
28367K. Nagamine, Y. Kanno, K. Sahara, T. Fujimoto, A. Yoshido, Y. Ishikawa, M. Terao, D. Kageyama and Y. Shintani, Proceedings of the National Academy of Sciences, 120:e2312124120. 2023-11-06 09:56:12.
A female-biased sex ratio is considered advantageous for the cytoplasmic elements that inhabit sexually reproducing organisms. There are numerous examples of bacterial symbionts in the arthropod cytoplasm that bias the host sex ratio toward females through various means, including feminization and male killing. Recently, maternally inherited RNA viruses belonging to the family Partitiviridae were found to cause male killing in moths and flies, but it was unknown whether male-killing viruses were restricted to Partitiviridae or could be found in other taxa. Here, we provide compelling evidence that a maternally inherited RNA virus, Spodoptera litura male-killing virus (SlMKV), selectively kills male embryos of the tobacco caterpillar Spodoptera litura, resulting in all-female broods. SlMKV injected into uninfected S. litura can also be inherited maternally and causes male killing. SlMKV has five genomic segments encoding seven open reading frames, has no homolog of known male-killing genes, and belongs to an unclassified group of arthropod-specific viruses closely related to Tolivirales. When transinfected into larvae, both male and female recipients allow SlMKV to proliferate, but only males die at the pupal stage. The viral RNA levels in embryonic and pupal male killing suggest that the mechanism of male killing involves the constitutive expression of viral products that are specifically lethal to males, rather than the male-specific expression of viral products. Our results, together with recent findings on male-killing partiti-like viruses, suggest that diverse viruses in arthropods tend to acquire male killing independently and that such viruses may be important components of intragenomic conflict in arthropods.
Gene drive in plants emerges from infancy
28152M. J. A. Awan, R. Z. Naqvi, I. Amin and S. Mansoor, Trends in Plant Science, 2023-10-18 11:43:35.
Selfish genetic elements (SGEs) display biased transmission to offspring. However, their breeding potential has remained obscure. Wang et al. recently reported a natural gene-drive system that can be harnessed to prevent hybrid incompatibility and to develop a synthetic gene-drive (SGD) system for crop improvement.
New perspectives on the causes and consequences of male meiotic drive
27827Courret, Cécile Wei, Xiaolu Larracuente, Amanda M., Current Opinion in Genetics & Development, 2023-09-11 08:34:27.
Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.
The role of conflict in shaping plant biodiversity
27753J. M. Coughlan, New Phytologist, 2023-09-04 07:45:46.
Although intrinsic postzygotic reproductive barriers can play a fundamental role in speciation, their underlying evolutionary causes are widely debated. One hypothesis is that incompatibilities result from genomic conflicts. Here, I synthesize the evidence that conflict generates incompatibilities in plants, thus playing a creative role in plant biodiversity. While much evidence supports a role for conflict in several classes of incompatibility, integrating knowledge of incompatibility alleles with natural history can provide further essential tests. Moreover, comparative work can shed light on the relative importance of conflict in causing incompatibilities, including the extent to which their evolution is repeatable. Together, these approaches can provide independent lines of evidence that conflict causes incompatibilities, cementing its role in plant speciation.
Proliferation and dissemination of killer meiotic drive loci
27711E. C. Lai and A. A. Vogan, Current Opinion in Genetics and Development, 82:102100. 2023-08-23 09:49:07.
Killer meiotic drive elements are selfish genetic entities that manipulate the sexual cycle to promote their own inheritance via destructive means. Two broad classes are sperm killers, typical of animals and plants, and spore killers, which are present in ascomycete fungi. Killer meiotic drive systems operate via toxins that destroy or disable meiotic products bearing the alternative allele. To avoid suicidal autotargeting, cells that bear these selfish elements must either lack the toxin target, or express an antidote. Historically, these systems were presumed to require large nonrecombining haplotypes to link multiple functional interacting loci. However, recent advances on fungal spore killers reveal that numerous systems are enacted by single genes, and similar molecular genetic studies in Drosophila pinpoint individual loci that distort gamete sex. Notably, many meiotic drivers duplicate readily, forming gene families that can have complex interactions within and between species, and providing substrates for their rapid functional diversification. Here, we summarize the known families of meiotic drivers in fungi and fruit flies, and highlight shared principles about their evolution and proliferation that promote the spread of these noxious genes.
Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis
27561H. Lee, P. Seo, S. Teklay, E. Yuguchi, E. D. Benetta, J. H. Werren and P. M. Ferree, Heredity, 2023-07-31 07:06:11.
B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR's own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp's genome also seem to evade chromatin disruption by PSR, suggesting that PSR's genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.
X chromosome drive is constrained by sexual selection and influences ornament evolution
27304K. A. Paczolt, G. T. Welsh and G. S. Wilkinson, Proceedings of the Royal Society B: Biological Sciences, 290:20230929. 2023-07-26 07:17:43.
Experimental evolution provides an integrative method for revealing complex interactions among evolutionary processes. One such interaction involves sex-linked selfish genetic elements and sexual selection. X-linked segregation distorters, a type of selfish genetic element, influence sperm transmission to increase in frequency and consequently alter the population sex ratio and the opportunity for sexual selection, while sexual selection may impact the spread of X-linked distorters. Here we manipulated sexual selection by controlling female mating opportunities and the presence of a distorting X chromosome in experimental lines of the stalk-eyed fly, Teleopsis dalmanni, over 11 generations. We find that removal of sexual selection leads to an increase in the frequency of the X-linked distorter and sex ratio across generations and that post-copulatory sexual selection alone is sufficient to limit the frequency of distorters. In addition, we find that male eyestalk length, a trait under pre-copulatory sexual selection, evolves in response to changes in the strength of sexual selection with the magnitude of the response dependent on X chromosome type and the frequency of distorting X chromosomes. These results reveal how a selfish X can interact with sexual selection to influence the evolution of sexually selected traits in multiple ways.
Impacts of sex ratio meiotic drive on genome structure and function in a stalk-eyed fly
26279J. A. Reinhardt, R. H. Baker, A. V. Zimin, C. Ladias, K. A. Paczolt, J. H. Werren, C. Y. Hayashi and G. S. Wilkinson, Genome Biology Evolution, 2023-06-26 10:49:44.
Stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio meiotic drive (SR) and impact the fitness of male and female carriers. Here, we assemble and describe a chromosome-level genome assembly of the stalk-eyed fly, Teleopsis dalmanni, to elucidate patterns of divergence associated with SR. The genome contains tens of thousands of transposable element (TE) insertions and hundreds of transcriptionally and insertionally active TE families. By resequencing pools of SR and ST males using short and long-reads, we find widespread differentiation and divergence between XSR and XST associated with multiple nested inversions involving most of the sex ratio haplotype. Examination of genomic coverage and gene expression data revealed seven X-linked genes with elevated expression and coverage in SR males. The most extreme and likely drive candidate involves an XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and associated with regulation of TE expression. In addition, we find evidence for rapid protein evolution between XSR and XST for testis expressed and novel genes, i.e. either recent duplicates or lacking a dipteran ortholog, including an X-linked duplicate of maelstrom, which is also involved in TE silencing. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.
Cell biology: Selfish B chromosomes unleashed by a dysfunctional chromosome segregation system
25563P. Ferree, Current Biology, 33:R431-R434. 2023-06-05 09:18:59.
A study in the fruit fly Drosophila melanogaster shows that a defective chromosome segregation system allows non-essential B chromosomes to transmit at higher-than-Mendelian frequencies.
Adaptation in the face of internal conflict: the paradox of the organism revisited
25238M. M. Patten, M. A. Schenkel and J. A. Ågren, Biological Reviews, 2023-05-19 07:37:20.
The paradox of the organism refers to the observation that organisms appear to function as coherent purposeful entities, despite the potential for within-organismal components like selfish genetic elements and cancer cells to erode them from within. While it is commonly accepted that organisms may pursue fitness maximisation and can be thought to hold particular agendas, there is a growing recognition that genes and cells do so as well. This can lead to evolutionary conflicts between an organism and the parts that reside within it. Here, we revisit the paradox of the organism. We first outline its conception and relationship to debates about adaptation in evolutionary biology. Second, we review the ways selfish elements may exploit organisms, and the extent to which this threatens organismal integrity. To this end, we introduce a novel classification scheme that distinguishes between selfish elements that seek to distort transmission versus those that seek to distort phenotypic traits. Our classification scheme also highlights how some selfish elements elude a multi-level selection decomposition using the Price equation. Third, we discuss how the organism can retain its status as the primary fitness-maximising agent in the face of selfish elements. The success of selfish elements is often constrained by their strategy and further limited by a combination of fitness alignment and enforcement mechanisms controlled by the organism. Finally, we argue for the need for quantitative measures of both internal conflicts and organismality.
A gene drive is a gene drive: the debate over lumping or splitting definitions
24910S. L. James, D. A. O'Brochta, F. Randazzo and O. Akbari, Nature Communications, 2023-03-29 12:22:20.
Gene drive technologies are being considered as a new approach to address a variety of currently intractable global problems, including to prevent disease transmission, reduce crop loss, and preserve biodiversity1. There are some outside the genetics research community who argue that wide use of the term “gene drive” to encompass selfish genetic elements found either in extant organisms (natural gene drives) or assembled in the laboratory (synthetic gene drives) will discourage the necessary scrutiny of risks that may be associated with the introduction of synthetic gene drives into free-living populations of target organisms2,3. Here we argue that the current definition is both scientifically sound and promotes good governance.
Gene Drives Are Coming
24887D. Lowe, Science, 2023-03-23 08:26:31.
Consider the “gene drive” idea - there are a lot of variations, but the general idea is that you introduce a genetic sequence into an organism that can bias (drive) its own inheritance into the next generation. This is a thumb-on-the-scale unnatural selection if ever there was one, because that biased inheritance is outside of any fitness advantage that the new sequence might bring with it. In fact, a number of gene drive ideas have the opposite sign, conferring catastrophic unfitness in order to wipe out pathogens and disease-vector organisms.Gene drives of various kinds show up in nature, though, when a gene has some sort of ability to control its own transmission. These are the so-called “selfish genes”, and some of these have no fitness advantage (or even some disadvantage) in the organisms themselves. There are a lot of potential mechanisms for this (see that link for a good review), but what you don’t see are the total-wipeout forms just mentioned, which is what we has humans might like to do to (say) mosquitos or tsetse flies. The advent of CRISPR-Cas9 technology has really brought a lot more attention to these ideas, because they make them far more possible, for better or worse.
Effects of Wolbachia on Transposable Element Expression Vary Between Drosophila melanogaster Host Genotypes
24871A. T. Eugénio, M. S. P. Marialva and P. Beldade, Genome Biology Evolution, 15. 2023-03-03 08:07:31.
Transposable elements (TEs) are repetitive DNA sequences capable of changing position in host genomes, thereby causing mutations. TE insertions typically have deleterious effects but they can also be beneficial. Increasing evidence of the contribution of TEs to adaptive evolution further raises interest in understanding what factors impact TE activity. Based on previous studies associating the bacterial endosymbiont Wolbachia with changes in the abundance of piRNAs, a mechanism for TE repression, and to transposition of specific TEs, we hypothesized that Wolbachia infection would interfere with TE activity. We tested this hypothesis by studying the expression of 14 TEs in a panel of 25 Drosophila melanogaster host genotypes, naturally infected with Wolbachia and annotated for TE insertions. The host genotypes differed significantly in Wolbachia titers inside individual flies, with broad-sense heritability around 20%, and in the number of TE insertions, which depended greatly on TE identity. By removing Wolbachia from the target host genotypes, we generated a panel of 25 pairs of Wolbachia-positive and Wolbachia-negative lines in which we quantified transcription levels for our target TEs. We found variation in TE expression that was dependent on Wolbachia status, TE identity, and host genotype. Comparing between pairs of Wolbachia-positive and Wolbachia-negative flies, we found that Wolbachia removal affected TE expression in 21.1% of the TE-genotype combinations tested, with up to 2.3 times differences in the median level of transcript. Our data show that Wolbachia can impact TE activity in host genomes, underscoring the importance this endosymbiont can have in the generation of genetic novelty in hosts.
Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes
24732C.-H. Chang, I. Mejia Natividad and H. S. Malik, eLife, 12:e85249. 2023-02-10 09:47:51.
Many animal species employ sperm nuclear basic proteins (SNBPs) or protamines to package sperm genomes tightly. SNBPs vary across animal lineages and evolve rapidly in mammals. We used a phylogenomic approach to investigate SNBP diversification in Drosophila species. We found that most SNBP genes in Drosophila melanogaster evolve under positive selection except for genes essential for male fertility. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved SNBP genes. For example, CG30056 is dispensable for male fertility despite being one of three SNBP genes universally retained in Drosophila species. We found 19 independent SNBP gene amplification events that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved SNBP genes, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions were more likely to degenerate or relocate back to autosomes. We hypothesize that autosomal SNBP genes suppress meiotic drive, whereas sex-chromosomal SNBP expansions lead to meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, genetic conflicts between sex chromosomes may drive SNBP rapid evolution during spermatogenesis in Drosophila species.
A selfish genetic element and its suppressor causes gross damage to testes in a fly
24697S. Lyth, A. Manser, G. Hurst, T. Price and R. Verspoor, bioRxiv, 2023.02.06.527273. 2023-02-06 12:34:06.
Selfish genetic elements (SGEs), specifically X-chromosome meiotic drive (XCMD), create huge conflicts within a hosts genome and can have profound effects on fertility. Suppressors are a common evolutionary response to XCMD to negate its costs. However, whether suppressors themselves can cause negative non-target effects remains understudied. Here, we examine whether the intragenomic conflicts created by XCMD and its suppressor affects gonad morphology in Drosophila subobscura. We found significant differences in testes, seminal vesicle, and accessory gland size depending on whether a male carried a non-driving X chromosome, an XCMD, and if the XCMD was suppressed. We also found the first evidence of extreme whole-organ damage to testes that is specifically associated with a suppressor of XCMD. Unlike other studies, our evidence suggests that XCMD in D. subobscura inflicts extreme damage on male gonads. This damage is most severe if both XCMD and its suppressor are both present. While costs of suppression have importance in theoretical models, they have largely been ignored in empirical XCMD systems. Overall, this study highlights that genetic conflict, created by SGEs and their suppressors, is a potent evolutionary force that can have major impacts on gonad development and gametogenesis.Competing Interest StatementThe authors have declared no competing interest.
Complicated expansion trajectories of insertion sequences and potential association with horizontal transfer of Wolbachia DNA
24573Y. H. Miao, D. W. Huang and J. H. Xiao, Zoological Research, 44:273-275. 2023-01-22 08:41:24.
Insertion sequences (ISs) are the simplest structural transposable elements (TEs) in prokaryotes, consisting only of a transposase coding sequence and its bilateral short terminal inverted repeats. Due to their gradually streamlined genomic construction, TEs rarely exist in the genomes of obligate endosymbionts. However, TE content, especially ISs, is abundant in the genome of Wolbachia bacteria, obligate endosymbionts widespread in arthropods and nematodes. Although IS indels are reported to affect genome structure and gene function in Wolbachia, the distribution patterns, sources, and transfer trajectories of ISs remain poorly understood. Furthermore, whether IS transposition is associated with dynamic horizontal transfer of Wolbachia DNA is still unclear. Based on distribution patterns in supergroup A Wolbachia strains, ISs accounted for 11% of the genome of the Wolbachia strain wWpum, one of the highest IS genome coverages reported for Wolbachia to date. Three types of ISs showed rapid expansion in wWpum, possibly due to horizontal transfer from other Wolbachia strain supergroups or more distant prokaryotes. We also found the first evidence that ISs can carry flanking Wolbachia sequences for transposition, resulting in the horizontal transfer of Wolbachia DNA into the eukaryotic genome, thus implying a potential association between ISs and horizontal gene transfer from endosymbionts to eukaryotes.
P-element invasions in Drosophila erecta; shed light on the establishment of host control over a transposable element
24320D. Selvaraju, F. Wierzbicki and R. Kofler, bioRxiv, 2022.12.22.521571. 2022-12-22 08:52:45.
To prevent the spread of transposable elements (TEs) hosts have developed sophisticated defence mechanisms. In mammals and invertebrates this defence mechanism operates through piRNAs. It is unclear how piRNA-based defences are established against invading TEs. According to the trap model, a TE insertion into a piRNA cluster, i.e. a distinct genomic locus, activates the host defence. Alternatively, siRNAs, generated by cleavage of dsRNA, may be the trigger for host control. To investigate this we introduced the P-element, one of the most widely studied eukaryotic transposons, into naïve lines of Drosophila erecta. We monitored the invasion in 3 replicates for more than 50 generations by sequencing the genomic DNA (using short and long-reads), the small RNAs and the transcriptome at regular intervals. A piRNA based host defence was rapidly established in 2 replicates but not in the third, where P-element copy numbers kept increasing for over 50 generations. We found that siRNAs emerged prior to piRNAs, supporting the view that siRNAs initiate host defence. However, neither insertions in piRNA clusters nor the formation of siRNAs were sufficient to stop the P-element. Instead the activation of the ping-pong cycle was shown to be crucial. We introduce a novel model, the crank-up model, which emphasizes activation of the ping-pong cycle as a critical event in establishing host control over a TE.Competing Interest StatementThe authors have declared no competing interest.
How Selfish Genes Succeed: Critical Insights Uncovered About Dangerous DNA
24318STOWERS INSTITUTE FOR MEDICAL RESEARCH, SciTechDaily, 2022-12-22 08:48:15.
New findings from the Stowers Institute for Medical Research uncover critical insights about how a dangerous selfish gene—considered to be a parasitic portion of DNA—functions and survives. Understanding this dynamic is a valuable resource for the broader community studying meiotic drive systems. A new study, published in PLoS Genetics on December 7, 2022, reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are designing synthetic drive systems for pathogenic pest control. Collective and collaborative advancement in understanding drive may one day lead to the eradication of pest populations that harm crops or even humans in the case of vector-borne diseases.
How selfish genes succeed
24155Stowers Institute for Medical Research, ScienceDaily, 2022-12-08 07:17:01.
A new study reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are designing synthetic drive systems for pathogenic pest control. Collective and collaborative advancement on understanding drive may one day lead to the eradication of pest populations that harm crops or even humans in the case of vector borne diseases.
Meiotic transmission patterns of additional genomic elements in Brachionus asplanchnoidis, a rotifer with intraspecific genome size variation
24116J. Blommaert and C.-P. Stelzer, Scientific Reports, 12:20900. 2022-12-03 09:37:14.
Intraspecific genome size (GS) variation in Eukaryotes is often mediated by additional, nonessential genomic elements. Physically, such additional elements may be represented by supernumerary (B-)chromosomes or by large heterozygous insertions into the regular chromosome set. Here we analyze meiotic transmission patterns of Megabase-sized, independently segregating genomic elements (ISEs) in Brachionus asplanchnoidis, a planktonic rotifer that displays an up to two-fold intraspecific GS variation due to variation in size and number of these elements. To gain insights into the meiotic transmission patterns of ISEs, we measured GS distributions of haploid males produced by individual mother clones using flow cytometry and compared these distributions to theoretical distributions expected under a range of scenarios. These scenarios considered transmission biases resembling (meiotic) drive, or cosegregation biases, e.g., if pairs of ISEs preferentially migrated towards the same pole during meiosis. We found that the inferred transmission patterns were diverse and ranged from positive biases (suggesting drive) to negative biases (suggesting drag), depending on rotifer clone and its ISE composition. Additionally, we obtained evidence for a negative cosegregation bias in some of the rotifer clones, i.e., pairs of ISEs exhibited an increased probability of migrating towards opposite poles during meiosis. Strikingly, these transmission and segregation patterns were more similar among members of a genetically homogeneous inbred line than among outbred members of the population. Comparisons between early and late stages of haploid male embryonic development (e.g., young synchronized male eggs vs. hatched males) showed very similar GS distributions, suggesting that transmission biases occur very early in male development, or even during meiosis. Very large genome size was associated with reduced male embryonic survival, suggesting that excessive amounts of ISEs might be detrimental to male fitness. Altogether, our results indicate considerable functional diversity of ISEs in B. asplanchnoidis, with consequences on meiotic transmission and embryonic survival.
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.
119-Million-Year-Old “Selfish” Genes Uncovered in Yeast
23785Stowers Institute for Medical Research, Technology Networks, 2022-10-19 07:15:07.
Meiotic drivers, a type of selfish gene, are indeed selfish. Present in the genomes of nearly all species, including humans, they unfairly transfer their genetic material to more than half of their offspring, sometimes leading to infertility, and decreased organism health. Because of their parasitic potential, their longevity over evolutionary time is believed to be short-lived, until now. New research from the Stowers Institute for Medical Research, in collaboration with the National Institute for Biological Sciences in Beijing, China, has uncovered a selfish gene family that has survived for over 100 million years—10 times longer than any meiotic driver ever identified—casting new doubt on established beliefs on how natural selection and evolution tackle these threatening sequences.
The wtf meiotic driver gene family has unexpectedly persisted for over 100 million years
23712M. De Carvalho, G. S. Jia, A. Nidamangala Srinivasa, R. B. Billmyre, Y. H. Xu, J. J. Lange, I. M. Sabbarini, L. L. Du and S. E. Zanders, eLife, 11. 2022-10-13 06:23:07.
Meiotic drivers are selfish elements that bias their own transmission into more than half of the viable progeny produced by a driver+/driver- heterozygote. Meiotic drivers are thought to exist for relatively short evolutionary timespans because a driver gene or gene family is often found in a single species or in a group of very closely related species. Additionally, drivers are generally considered doomed to extinction when they spread to fixation or when suppressors arise. In this study, we examine the evolutionary history of the wtf meiotic drivers first discovered in the fission yeast Schizosaccharomyces pombe. We identify homologous genes in three other fission yeast species, S. octosporus, S. osmophilus, and S. cryophilus, which are estimated to have diverged over 100 million years ago from the S. pombe lineage. Synteny evidence supports that wtf genes were present in the common ancestor of these four species. Moreover, the ancestral genes were likely drivers as wtf genes in S. octosporus cause meiotic drive. Our findings indicate that meiotic drive systems can be maintained for long evolutionary timespans.
Selfish evolution of placental hormones
23534G. Keegan and M. M. Patten, Evolution, Medicine, and Public Health, 10:391-397. 2022-09-10 05:50:19.
We hypothesize that some placental hormones—specifically those that arise by tandem duplication of genes for maternal hormones—may behave as gestational drivers, selfish genetic elements that encourage the spontaneous abortion of offspring that fail to inherit them. Such drivers are quite simple to evolve, requiring just three things: a decrease in expression or activity of some essential maternal hormone during pregnancy; a compensatory increase in expression or activity of the homologous hormone by the placenta; and genetic linkage between the two effects. Gestational drive may therefore be a common selection pressure experienced by any of the various hormones of mammalian pregnancy that have arisen by tandem gene duplication. We examine the evolution of chorionic gonadotropin in the human lineage in light of this hypothesis. Finally, we postulate that some of the difficulties of human pregnancy may be a consequence of the action of selfish genes.We show how placental hormones that have arisen via tandem gene duplication from maternally produced hormones may subsequently experience selection as selfish genetic elements and spread through populations despite causing reproductive inefficiency. We examine the implications of this hypothesis and point to some empirical tests.
On the Mechanistic Basis of Killer Meiotic Drive in Fungi
23530S. J. Saupe and H. Johannesson, Annual Review of Microbiology, 76:305-323. 2022-09-08 05:38:51.
Spore killers are specific genetic elements in fungi that kill sexual spores that do not contain them. A range of studies in the last few years have provided the long-awaited first insights into the molecular mechanistic aspects of spore killing in different fungal models, including both yeast-forming and filamentous Ascomycota. Here we describe these recent advances, focusing on the wtf system in the fission yeast Schizosaccharomyces pombe; the Sk spore killers of Neurospora species; and two spore-killer systems in Podospora anserina, Spok and [Het-s]. The spore killers appear thus far mechanistically unrelated. They can involve large genomic rearrangements but most often rely on the action of just a single gene. Data gathered so far show that the protein domains involved in the killing and resistance processes differ among the systems and are not homologous. The emerging picture sketched by these studies is thus one of great mechanistic and evolutionary diversity of elements that cheat during meiosis and are thereby preferentially inherited over sexual generations.
B Chromosomes in Psalidodon scabripinnis (Characiformes, Characidae) Species Complex
23552D. Silva, J. P. Castro, C. A. G. Goes, R. Utsunomia, M. R. Vidal, C. N. Nascimento, L. F. Lasmar, F. G. Paim, L. B. Soares, C. Oliveira, F. Porto-Foresti, R. F. Artoni and F. Foresti, Animals (Basel), 12. 2022-08-25 06:15:39.
B chromosomes are extra-genomic components of cells found in individuals and in populations of some eukaryotic organisms. They have been described since the first observations of chromosomes, but several aspects of their biology remain enigmatic. Despite being present in hundreds of fungi, plants, and animal species, only a small number of B chromosomes have been investigated through high-throughput analyses, revealing the remarkable mechanisms employed by these elements to ensure their maintenance. Populations of the Psalidodon scabripinnis species complex exhibit great B chromosome diversity, making them a useful material for various analyses. In recent years, important aspects of their biology have been revealed. Here, we review these studies presenting a comprehensive view of the B chromosomes in the P. scabripinnis complex and a new hypothesis regarding the role of the B chromosome in the speciation process.
Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives
23416M. Melesse Vergara, J. Labbé and J. Tannous, BioDesign Research, 2022:9853416. 2022-08-09 07:29:59.
Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constantgenetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decadesago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes formedicine, agriculture, and ecology in combating diseases. Following itsfirst discovery, several naturally occurring selfishgenetic elements were identified and several gene drive mechanisms that could attain relatively high threshold populationreplacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive researchwith a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genomeengineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural genedrives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing syntheticdrive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight themajor applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, andmicroorganisms.
Non-Mendelian transmission of accessory chromosomes in fungi
23305J. Komluski, E. H. Stukenbrock and M. Habig, Chromosome Research, 2022-07-26 07:44:07.
Non-Mendelian transmission has been reported for various genetic elements, ranging from small transposons to entire chromosomes. One prime example of such a transmission pattern are B chromosomes in plants and animals. Accessory chromosomes in fungi are similar to B chromosomes in showing presence/absence polymorphism and being non-essential. How these chromosomes are transmitted during meiosis is however poorly understood-despite their often high impact on the fitness of the host. For several fungal organisms, a non-Mendelian transmission or a mechanistically unique meiotic drive of accessory chromosomes have been reported. In this review, we provide an overview of the possible mechanisms that can cause the non-Mendelian transmission or meiotic drives of fungal accessory chromosomes. We compare processes responsible for the non-Mendelian transmission of accessory chromosomes for different fungal eukaryotes and discuss the structural traits of fungal accessory chromosomes affecting their meiotic transmission. We conclude that research on fungal accessory chromosomes, due to their small size, ease of sequencing, and epigenetic profiling, can complement the study of B chromosomes in deciphering factors that influence and regulate the non-Mendelian transmission of entire chromosomes.
“Selfish Genetic Elements” – Supergene Wreaks Havoc in a Genome
23302University of Rochester, SciTechDaily, 2022-07-25 07:37:40.
“Selfish genetic elements” litter the human genome. They do not seem to benefit their hosts but instead seek only to propagate themselves. These selfish genetic elements can wreak havoc. For example, they can distort sex ratios, impair fertility, cause harmful mutations, and even potentially cause population extinction. Biologists have for the first time used population genomics to shed light on the evolution and consequences of a selfish genetic element known as Segregation Distorter (SD). These researchers at the University of Rochester, include Amanda Larracuente, an associate professor of biology, and Daven Presgraves, a University Dean’s Professor of Biology. In a paper published recently in the journal eLife, the scientists report that SD has caused dramatic changes in chromosome organization and genetic diversity.
What can we learn from selfish loci that break Mendel’s law?
23349S. E. Zanders, PLOS Biology, 20:e3001700. 2022-07-19 07:31:24.
Mendel’s law of segregation provides a critical foundation for genetic inquiry It is not, however, without exceptions Historically, 2 such exceptions (sex chromosome linkage and chromosome missegregation in meiosis) were used by Drosophila geneticists to help demonstrate that genes are carried on chromosomes Looking forward, modern geneticists interested in understanding the mechanisms of heredity have much to learn from additional exceptions to Mendel’s law In particular, selfish genes that break Mendel’s law of segregation to gain a transmission advantage into the next generation are likely to be oversized contributors to shaping the process of sexual reproduction These selfish genes exploit reproduction such that a given selfish locus is transmitted to more than half of the offspring produced by an organism There are a variety of selfish DNAs, but here I will focus on transposable elements and drive loci as examples Transposable elements can generate novel copies of themselves using copy and paste or cut and paste mechanisms Importantly, transposable elements are selected to mobilize in the germline as that allows new copies to be passed on to subsequent generations Drive loci preferentially bias their own transmission such that a driver+ /driver− heterozygote will pass the driver+ allele to more than half of its viable progeny Drivers are diverse and can act during meiosis, gametogenesis, or post-fertilization Both transposable elements and drivers are found throughout eukaryotes, including humans
Isolation of rfk-2 (UV) , a mutation that blocks spore killing by Neurospora Spore killer-3
23382A. Velazquez, E. Webber, D. O'Neil, T. Hammond and N. Rhoades, MicroPublication Biology, 2022-07-17 07:16:34.
Neurospora Spore killer-3 ( Sk-3 ) is a selfish genetic element that kills spores to achieve gene drive. Here, to help identify Sk-3’s killer, we performed a genetic screen for required for killing (rfk) mutations (see methods). The genetic screen uses Sk‑3 rskΔ × SkS crosses, which abort development before the production of viable ascospores (Hammond et al. 2012; Harvey et al. 2014). We isolated a few candidate rfk mutations with our genetic screen and chose the most promising candidate, rfk-2UV, for additional analysis. As demonstrated in Figure 1 (A and B), rfk-2UV disrupts spore killing and gene drive. To determine the approximate genomic location of rfk-2UV, we performed two sets of three-point crosses (Figure 1C). Recombination analysis of 213 offspring from the first set of crosses (rfk-2UV hphA × mus-52Δ) indicates that rfk-2UV islocated 2.8 cM from hphA and 15.0 cM from mus-52Δ (Figure 1D). For the second set of crosses (rfk-2UV hphB × mus-52Δ), recombination analysis of 186 offspring indicates that rfk-2UV is located 7.5 cM from hphB and 16.1 cM from mus-52Δ (Figure 1E). The significance of this discovery with respect to Sk-3 evolution is discussed.
A Toxin-Antidote Selfish Element Increases Fitness of its Host
23798L. Long, W. Xu, A. B. Paaby and P. T. McGrath, bioRxiv, 2022.07.15.500229. 2022-07-15 07:35:20.
Selfish genetic elements can promote their transmission at the expense of individual survival, creating conflict between the element and the rest of the genome. Recently, a large number of toxin-antidote (TA) post-segregation distorters have been identified in non-obligate outcrossing nematodes. Their origin and the evolutionary forces that keep them at intermediate population frequencies are poorly understood. Here, we study a TA element in C. elegans called peel-1/zeel-1. Two major haplotypes of this locus, with and without the selfish element, segregate in C. elegans. Here we study the fitness consequences of the peel-1/zeel-1 element outside of its role in gene drive in non-outcrossing animals. We demonstrate that loss of the toxin peel-1 decreased fitness of hermaphrodites and resulted in reductions in fecundity and body size. This fitness advantage is independent of the antidote zeel-1, suggesting that a distinct peel-1 pathway plays a biological role. This work demonstrates that a TA element can provide a fitness benefit to its hosts, either during their initial evolution or by being co-opted by the animals following their selfish spread. These findings guide our understanding on how TA elements can remain in a population where gene drive is minimized, helping resolve the mystery of prevalent TA elements in selfing animals.Competing Interest StatementThe authors have declared no competing interest.
Iterative evolution of supergene-based social polymorphism in ants
22899T. Kay, Q. Helleu and L. Keller, Philos Trans R Soc Lond B Biol Sci, 377:20210196. 2022-06-13 06:17:44.
Species commonly exhibit alternative morphs, with individual fate being determined during development by either genetic factors, environmental cues or a combination thereof. Ants offer an interesting case study because many species are polymorphic in their social structure. Some colonies contain one queen while others contain many queens. This variation in queen number is generally associated with a suite of phenotypic and life-history traits, including mode of colony founding, queen lifespan, queen-worker dimorphism and colony size. The basis of this social polymorphism has been studied in five ant lineages, and remarkably social morph seems to be determined by a supergene in all cases. These 'social supergenes' tend to be large, having formed through serial inversions, and to comprise hundreds of linked genes. They have persisted over long evolutionary timescales, in multiple lineages following speciation events, and have spread between closely related species via introgression. Their evolutionary dynamics are unusually complex, combining recessive lethality, spatially variable selection, selfish genetic elements and non-random mating. Here, we synthesize the five cases of supergene-based social polymorphism in ants, highlighting interesting commonalities, idiosyncrasies and implications for the evolution of polymorphisms in general. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Unbalanced selection: the challenge of maintaining a social polymorphism when a supergene is selfish
22895A. G. Tafreshi, S. P. Otto and M. Chapuisat, Philos Trans R Soc Lond B Biol Sci, 377:20210197. 2022-06-13 06:11:36.
Supergenes often have multiple phenotypic effects, including unexpected detrimental ones, because recombination suppression maintains associations among co-adapted alleles but also allows the accumulation of recessive deleterious mutations and selfish genetic elements. Yet, supergenes often persist over long evolutionary periods. How are such polymorphisms maintained in the face of selection, drive and drift? We present a population genetic model that investigates the conditions necessary for a stable polymorphic equilibrium when one of the supergene haplotypes is a selfish genetic element. The model fits the characteristics of the Alpine silver ant, Formica selysi, in which a large supergene underlies colony social organization, and one haplotype distorts Mendelian transmission by killing progeny that did not inherit it. The model shows that such maternal-effect killing strongly limits the maintenance of social polymorphism. Under random mating, transmission ratio distortion prevents rare single-queen colonies from invading populations of multiple-queen colonies, regardless of the fitness of each genotype. A stable polymorphic equilibrium can, however, be reached when high rates of assortative mating are combined with large fitness differences among supergene genotypes. The model reveals that the persistence of the social polymorphism is non-trivial and expected to occur only under restrictive conditions that deserve further empirical investigation. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Supergene potential of a selfish centromere
22893F. Finseth, K. Brown, A. Demaree and L. Fishman, Philos Trans R Soc Lond B Biol Sci, 377:20210208. 2022-06-13 06:07:46.
Selfishly evolving centromeres bias their transmission by exploiting the asymmetry of female meiosis and preferentially segregating to the egg. Such female meiotic drive systems have the potential to be supergenes, with multiple linked loci contributing to drive costs or enhancement. Here, we explore the supergene potential of a selfish centromere (D) in Mimulus guttatus, which was discovered in the Iron Mountain (IM) Oregon population. In the nearby Cone Peak population, D is still a large, non-recombining and costly haplotype that recently swept, but shorter haplotypes and mutational variation suggest a distinct population history. We detected D in five additional populations spanning more than 200 km; together, these findings suggest that selfish centromere dynamics are widespread in M. guttatus. Transcriptome comparisons reveal elevated differences in expression between driving and non-driving haplotypes within, but not outside, the drive region, suggesting large-scale cis effects of D's spread on gene expression. We use the expression data to refine linked candidates that may interact with drive, including Nuclear Autoantigenic Sperm Protein (NASP(SIM3)), which chaperones the centromere-defining histone CenH3 known to modify Mimulus drive. Together, our results show that selfishly evolving centromeres may exhibit supergene behaviour and lay the foundation for future genetic dissection of drive and its costs. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Active genetics comes alive
22888V. M. Gantz and E. Bier, BioEssays, 2022-06-09 09:28:52.
Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based ?active genetic? elements developed in 2015 bypassed the fundamental rules of traditional genetics. Inherited in a super-Mendelian fashion, such selfish genetic entities offered a variety of potential applications including: gene-drives to disseminate gene cassettes carrying desired traits throughout insect populations to control disease vectors or pest species, allelic drives biasing inheritance of preferred allelic variants, neutralizing genetic elements to delete and replace or to halt the spread of gene-drives, split-drives with the core constituent Cas9 endonuclease and guide RNA (gRNA) components inserted at separate genomic locations to accelerate assembly of complex arrays of genetic traits or to gain genetic entry into novel organisms (vertebrates, plants, bacteria), and interhomolog based copying systems in somatic cells to develop tools for treating inherited or infectious diseases. Here, we summarize the substantial advances that have been made on all of these fronts and look forward to the next phase of this rapidly expanding and impactful field.
Non-Mendelian segregation and transmission drive of B chromosomes
22725J. P. M. Camacho, Chromosome Research, 2022-06-03 07:58:27.
Selfish genetic elements (SGE) get a transmission advantage (drive) thanks to their non-Mendelian inheritance. Here I identify eight steps during the reproductive cycle that can be subverted by SGEs to thrive in natural populations. Even though only three steps occur during meiosis, most cases of segregation distortion are considered “meiotic drive sensu lato.” As this is a source of unnecessary contradictions, I suggest always using the term “transmission ratio distortion” (TRD). Chromosomal SGEs (e.g., B chromosomes) exhibit almost all types of TRD. In plants, the best-studied type of TRD for B chromosomes occurs post-meiotically during male gametophyte maturation. However, in animals, the two main types are pre-meiotic and meiotic TRDs, in all cases associated with gonotaxis (i.e., a preference of B chromosomes for germ cells). Frequently, TRD drivers in genic SGEs (e.g., t-alleles and segregation distorters in Drosophila) are paralogous copies of genes from the standard genome, whereas their targets can be other genes or satellite DNA (satDNA). As B chromosomes are often rich in satDNA and contain paralogous copies of A chromosome genes, perhaps their drive mechanisms are similar to those of genic SGEs. So far, the only association between a B chromosome gene and TRD is the gene haplodizer in Nasonia vitripennis. The discovery of B-genes controlling B-drive in other species does not appear to be far off, but experimental crosses will be needed to simultaneously test the TRD of a given B chromosome and the expression of its genes.
Mendelian nightmares: the germline-restricted chromosome of songbirds
21724P. Borodin, A. Chen, W. Forstmeier, S. Fouché, L. Malinovskaya, Y. Pei, R. Reifová, F. J. Ruiz-Ruano, S. A. Schlebusch, M. Sotelo-Muñoz, A. Torgasheva, N. Vontzou and A. Suh, Chromosome Res, 2022-04-13 09:33:56.
Germline-restricted chromosomes (GRCs) are accessory chromosomes that occur only in germ cells. They are eliminated from somatic cells through programmed DNA elimination during embryo development. GRCs have been observed in several unrelated animal taxa and show peculiar modes of non-Mendelian inheritance and within-individual elimination. Recent cytogenetic and phylogenomic evidence suggests that a GRC is present across the species-rich songbirds, but absent in non-passerine birds, implying that over half of all 10,500 bird species have extensive germline/soma genome differences. Here, we review recent insights gained from genomic, transcriptomic, and cytogenetic approaches with regard to the genetic content, phylogenetic distribution, and inheritance of the songbird GRC. While many questions remain unsolved in terms of GRC inheritance, elimination, and function, we discuss plausible scenarios and future directions for understanding this widespread form of programmed DNA elimination.
The non-Mendelian behavior of plant B chromosomes
21722J. Chen, J. A. Birchler and A. Houben, Chromosome Res, 2022-04-12 09:30:19.
B chromosomes, also known as supernumerary chromosomes, are dispensable elements in the genome of many plants, animals, and fungi. Many B chromosomes have evolved one or more drive mechanisms to transmit themselves at a higher frequency than predicted by Mendelian genetics, and these mechanisms counteract the tendency of non-essential genetic elements to be lost over time. The frequency of Bs in a population results from a balance between their effect on host fitness and their transmission rate. Here, we will summarize the findings of the drive process of plant B chromosomes, focusing on maize and rye.
B-A Chromosome Translocations Possessing an A Centromere Partly Overcome the Root-Restricted Process of Chromosome Elimination in Aegilops speltoides
21726D. Li, A. Ruban, J. Fuchs, H. Kang and A. Houben, Frontiers in Cell and Developmental Biology, 10. 2022-03-28 09:37:44.
Some eukaryotes exhibit dramatic genome size differences between cells of different organs, resulting from the programmed elimination of chromosomes. Aegilops speltoides is an annual diploid species from the Poaceae family, with a maximum number of eight B chromosomes (Bs) in addition to its inherent seven pairs of standard A chromosomes (As). The Bs of this species undergo precise elimination in roots early in embryo development. In areal parts of the plant, the number of Bs is stable. To affect the root restricted process of B chromosome elimination, we employed X-ray mutagenesis, and different types of restructured Bs were identified. Standard Bs were observed in all analyzed shoots of mutagenized plants, while B-A translocations were only observed in 35.7% of F1 plants. In total 40 different B variants inconsistently escaped the elimination process in roots. As a result, mosaicism of B chromosome variants was found in roots. Only a small B chromosome fragment fused to an A chromosome was stably maintained in roots and shoots across F1 to F3 generations. The absence of B-A translocation chromosomes possessing a derived B centromere in root cells implies that the centromere of the B is a key component of the chromosome elimination process.
Evolution of eukaryotic centromeres by drive and suppression of selfish genetic elements
21559T. Kumon and M. A. Lampson, Seminars in Cell and Developmental Biology, 2022-03-25 12:12:40.
Despite the universal requirement for faithful chromosome segregation, eukaryotic centromeres are rapidly evolving. It is hypothesized that rapid centromere evolution represents an evolutionary arms race between selfish genetic elements that drive, or propagate at the expense of organismal fitness, and mechanisms that suppress fitness costs. Selfish centromere DNA achieves preferential inheritance in female meiosis by recruiting more effector proteins that alter spindle microtubule interaction dynamics. Parallel pathways for effector recruitment are adaptively evolved to suppress functional differences between centromeres. Opportunities to drive are not limited to female meiosis, and selfish transposons, plasmids and B chromosomes also benefit by maximizing their inheritance. Rapid evolution of selfish genetic elements can diversify suppressor mechanisms in different species that may cause hybrid incompatibility.
GeneConvene Global Collaborative Webinar Series | Genetic Drive Systems in Nature
20552David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2022-03-09 14:02:21.
Intra genomic genetic conflicts are ubiquitous in nature and have shaped and continue to shape the evolution of plants, animals, and microbes. These conflicts can result in preferential transmission - drive - of genes, various genetic elements, and even whole chromosomes. Interest in drive systems extends beyond the basic sciences to technologists who are exploring natural and synthetic drives as agents to suppress or modify species in nature. This webinar series will explore the variety of drive systems found in nature, mechanisms responsible for drive and impacts of drive on behavior and evolution..
Endosymbionts moderate constrained sex allocation in a haplodiploid thrips species in a temperature-sensitive way
20394A. Katlav, D. T. Nguyen, J. L. Morrow, R. N. Spooner-Hart and M. Riegler, Heredity, 9. 2022-02-03 09:32:33.
Maternally inherited bacterial endosymbionts that affect host fitness are common in nature. Some endosymbionts colonise host populations by reproductive manipulations (such as cytoplasmic incompatibility; CI) that increase the reproductive fitness of infected over uninfected females. Theory predicts that CI-inducing endosymbionts in haplodiploid hosts may also influence sex allocation, including in compatible crosses, however, empirical evidence for this is scarce. We examined the role of two common CI-inducing endosymbionts, Cardinium and Wolbachia, in the sex allocation of Pezothrips kellyanus, a haplodiploid thrips species with a split sex ratio. In this species, irrespective of infection status, some mated females are constrained to produce extremely male-biased broods, whereas other females produce extremely female-biased broods. We analysed brood sex ratio of females mated with males of the same infection status at two temperatures. We found that at 20 degrees C the frequency of constrained sex allocation in coinfected pairs was reduced by 27% when compared to uninfected pairs. However, at 25 degrees C the constrained sex allocation frequency increased and became similar between coinfected and uninfected pairs, resulting in more male-biased population sex ratios at the higher temperature. This temperature-dependent pattern occurred without changes in endosymbiont densities and compatibility. Our findings indicate that endosymbionts affect sex ratios of haplodiploid hosts beyond the commonly recognised reproductive manipulations by causing female-biased sex allocation in a temperature-dependent fashion. This may contribute to a higher transmission efficiency of CI-inducing endosymbionts and is consistent with previous models that predict that CI by itself is less efficient in driving endosymbiont invasions in haplodiploid hosts.
Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila
19441G. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 118:e2107413118. 2021-12-01 20:58:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. As a consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-ClvRdbe are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli.
Molecular Mechanisms and Evolutionary Consequences of Spore Killers in Ascomycetes
19237S. Zanders and H. Johannesson, Microbiology and Molecular Biology Reviews, 2021-11-10 22:05:58.
In this review, we examine the fungal spore killers. These are meiotic drive elements that cheat during sexual reproduction to increase their transmission into the next generation. Spore killing has been detected in a number of ascomycete genera, including Podospora, Neurospora, Schizosaccharomyces, Bipolaris, and Fusarium. There have been major recent advances in spore killer research that have increased our understanding of the molecular identity, function, and evolutionary history of the known killers. The spore killers vary in the mechanism by which they kill and are divided into killer-target and poison-antidote drivers. In killer-target systems, the drive locus encodes an element that can be described as a killer, while the target is an allele found tightly linked to the drive locus but on the nondriving haplotype. The poison-antidote drive systems encode both a poison and an antidote element within the drive locus. The key to drive in this system is the restricted distribution of the antidote: only the spores that inherit the drive locus receive the antidote and are rescued from the toxicity of the poison. Spore killers also vary in their genome architecture and can consist of a single gene or multiple linked genes. Due to their ability to distort meiosis, spore killers gain a selective advantage at the gene level that allows them to increase in frequency in a population over time, even if they reduce host fitness, and they may have significant impact on genome architecture and macroevolutionary processes such as speciation.
A Maternal-Effect Toxin Affects Epithelial Differentiation and Tissue Mechanics in Caenorhabditis elegans
19128C. Lehmann and C. Pohl, Frontiers in Cell and Developmental Biology, 9. 2021-10-14 14:25:20.
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These elements seem to act as modification-rescue systems, also called toxin/antidote pairs. Here we show that the maternal-effect toxin/zygotic antidote pair sup-35/pha-1 is required for proper expression of apical junction (AJ) components in epithelia and that sup-35 toxicity increases when pathways that establish and maintain basal epithelial characteristics, die-1, elt-1, lin-26, and vab-10, are compromised. We demonstrate that pha-1(e2123) embryos, which lack the antidote, are defective in epidermal morphogenesis and frequently fail to elongate. Moreover, seam cells are frequently misshaped and mispositioned and cell bond tension is reduced in pha-1(e2123) embryos, suggesting altered tissue material properties in the epidermis. Several aspects of this phenotype can also be induced in wild-type embryos by exerting mechanical stress through uniaxial loading. Seam cell shape, tissue mechanics, and elongation can be restored in pha-1(e2123) embryos if expression of the AJ molecule DLG-1/Discs large is reduced. Thus, our experiments suggest that maternal-effect toxicity disrupts proper development of the epidermis which involves distinct transcriptional regulators and AJ components.
Meiotic self-pairing of the Psalidodon (Characiformes, Characidae) iso-B chromosome: A successful perpetuation mechanism
18905D. Silva, C. Araya-Jaime, M. Yamashita, M. R. Vidal, C. Oliveira, F. Porto-Foresti, R. F. Artoni and F. Foresti, Genetics and Molecular Biology, 44:e20210084. 2021-10-08 14:29:15.
B chromosomes are non-essential additional genomic elements present in several animal and plant species. In fishes, species of the genus Psalidodon (Characiformes, Characidae) harbor great karyotype diversity, and multiple populations carry different types of non-essential B chromosomes. This study analyzed how the dispensable supernumerary B chromosome of Psalidodon paranae behaves during meiosis to overcome checkpoints and express its own meiosis-specific genes. We visualized the synaptonemal complexes of P. paranae individuals with zero, one, or two B chromosomes using immunodetection with anti-medaka SYCP3 antibody and fluorescence in situ hybridization with a (CA)15 microsatellite probe. Our results showed that B chromosomes self-pair in cells containing only one B chromosome. In cells with two identical B chromosomes, these elements remain as separate synaptonemal complexes or close self-paired elements in the nucleus territory. Overall, we reveal that B chromosomes can escape meiotic silencing of unsynapsed chromatin through a self-pairing process, allowing expression of their own genes to facilitate regular meiosis resulting in fertile individuals. This behavior, also seen in other congeneric species, might be related to their maintenance throughout the evolutionary history of Psalidodon.
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.
Unravelling the mystery of female meiotic drive: where we are
18263F. E. Clark and T. Akera, Open Biol, 11:210074. 2021-09-02 13:30:18.
Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.
Parallel pathways for recruiting effector proteins determine centromere drive and suppression
18266T. Kumon, J. Ma, R. B. Akins, D. Stefanik, C. E. Nordgren, J. Kim, M. T. Levine and M. A. Lampson, Cell, 2021-08-26 13:45:10.
Selfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this "centromere drive." In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting the kinetochore pathway with a divergent allele of CENP-C reduces functional differences between centromeres, whereas disrupting heterochromatin by CENP-B deletion amplifies the differences. Molecular evolution analyses using Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions.
Haldane’s duel: intragenomic conflict, selfish Y chromosomes and speciation
17509S. W. Roy, Trends in Genetics, 2021-06-21 14:14:05.
Haldane?s rule, which states that the heterogametic sex (XY or ZW females) fares more poorly in interspecific hybrids, is generally attributed to absence of one of the two species' X/Z chromosomes. However, Haldane?s rule is also observed in mouse placentas despite paternal X silencing. This pattern could reflect Y chromosomes having evolved to promote growth due to maternal?paternal conflict. If so, balanced sex investment arises from a complex intra- and intergenomic duel.
Researchers report reference genome for maize B chromosome
17172Chinese Academy of Sciences, Phys Org, 2021-05-31 19:46:00.
Three groups recently reported a reference sequence for the supernumerary B chromosome in maize in a study published online in PNAS. Dr. James Birchler's group from University of Missouri, Dr. Jan Barto's group from Institute of Experimental Botany of the Czech Academy of Sciences and Dr. Han Fangpu's group from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences worked collaboratively on the study. Supernumerary B chromosomes persist in thousands of plant and animal genomes despite being nonessential. They are maintained in populations by mechanisms of "drive" that make them inherited at higher than typical Mendelian rates. Key properties such as its origin, evolution, and the molecular mechanism for its accumulation in maize have remained unclear even though such chromosomes have been a potent tool for studying maize genetics.
Selfish gene leaves bacteria behind
16967A. York, Nature Reviews Microbiology, 2021-05-05 15:16:52.
Mitochondrial genome evolution is characterized by functional streamlining and gene loss, and gain-of-function gene transfers into the mitochondrial genome are considered rare events. Milner, et al. identified a functional restriction modification (R-M) system in the mitochondrial genome of a marine protist that originated in bacteria. The type II R-M system was found in the mitochondrial genome of a marine heterotrophic katablepharid protist, and phylogenetic analyses suggest that the selfish genetic element consisting of an HpaII-like endonuclease and a cognate cytosine methyltransferase originated in bacteria within or related to Flavobacteriaceae. The authors showed that the R-M system is functional in both bacteria and yeast, and that a toxin–antitoxin relationship exists between the two proteins. The authors posit that the toxin–antitoxin function of the R-M system may have been co-opted to control biased or uniparental inheritance of mitochondria.
Mechanistically comparing reproductive manipulations caused by selfish chromosomes and bacterial symbionts
16958E. Dalla Benetta, O. S. Akbari and P. M. Ferree, Heredity, 126:707-716. 2021-05-01 14:52:23.
Insects naturally harbor a broad range of selfish agents that can manipulate their reproduction and development, often leading to host sex ratio distortion. Such effects directly benefit the spread of the selfish agents. These agents include two broad groups: bacterial symbionts and selfish chromosomes. Recent studies have made steady progress in uncovering the cellular targets of these agents and their effector genes. Here we highlight what is known about the targeted developmental processes, developmental timing, and effector genes expressed by several selfish agents. It is now becoming apparent that: (1) the genetic toolkits used by these agents to induce a given reproductive manipulation are simple, (2) these agents target sex-specific cellular processes very early in development, and (3) in some cases, similar processes are targeted. Knowledge of the molecular underpinnings of these systems will help to solve long-standing puzzles and provide new tools for controlling insect pests.
A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist
16970D. A.-O. Milner, J. A.-O. Wideman, C. A.-O. Stairs, C. D. Dunn and T. A.-O. Richards, PLoS Biology, 2021-04-23 15:33:12.
The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss. Therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrion-encoded RM system can function as a toxin-antitoxin selfish element, and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance. FAU - Milner, David S
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.
Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance
16290A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan, PLOS Genetics, 17:e1009321. 2021-01-29 21:53:25.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.
Widespread haploid-biased gene expression enables sperm-level natural selection
16009K. Bhutani, K. Stansifer, S. Ticau, L. Bojic, A.-C. Villani, J. Slisz, C. M. Cremers, C. Roy, J. Donovan, B. Fiske and R. C. Friedman, Science, eabb1723. 2021-01-14 14:15:08.
Here, we show that a large class of mammalian genes are not completely shared across these bridges. We term these genes “genoinformative markers” (GIMs) and show that a subset can act as selfish genetic elements that spread alleles unevenly through murine, bovine, and human populations. We identify evolutionary pressure to avoid conflict between sperm and somatic function as GIMs are enriched for testis-specific gene expression, paralogs, and isoforms.
Self-Deleting Genes Project To Tackle Mosquito-Borne Diseases
15923D. Ozdemir, INTERESTING ENGINEERING, 2021-01-08 18:58:57.
Did you know that mosquitoes kill at least 725,000 persons every year? They truly are one of the world's deadliest animals which is the reason why scientists from all around are trying to find new ways of dealing with them. Controlling mosquito populations and preventing them from transmitting disease at times through genetic engineering is one way of doing that. Now, a new Texas A&M AgriLife Research project has plans of enabling "test runs" of the proposed changes in mosquitoes that are automatically deleted from their genetic code. Researchers have used genetic engineering in the past to modify mosquitoes in a way that they pass on infertility, don't grow wings, can't spread malaria, or have impaired smell. However, as New Atlas reports, this sort of modification can have harmful consequences that may be impossible to reverse when released into the wild.
Edit, undo: Temporary gene editing could help solve the mosquito problem
15900L. Dormehl, digitaltrends, 2020-12-31 14:22:29.
But if SyFy original movies have taught us anything, it’s that genetically tweaking organisms and then releasing them can… well, not go quite according to plan.With that in mind, a new Texas A&M AgriLife Research project seeks to test out genetic modifications of mosquitos that would delete themselves from the genetic code after a certain period. This means that “test runs” of genetic changes could be made, knowing that everything will reset to normal after a designated period like one year (which equates to around 20 generations of mosquito).
Self-deleting genes promise risk-free genetic engineering of mosquitoes
15852D. Quick, New Atlas, 2020-12-29 18:53:49.
A new project by Texas A&M AgriLife Research is looking to enable "test runs" of genetic changes to mosquitoes that are automatically deleted. Various angles of attack using genetic engineering to combat mosquitoes have been pursued in recent years, including modifying them so they pass on infertility, don't grow wings, can't spread malaria or have impaired smell. But making genetic modifications to an organism and then releasing them into the wild runs the risk of unintended and harmful consequences that may be difficult to reverse. That's where the new Texas A&M AgriLife Research project comes in. It is looking to enable "test runs" of genetic modifications that would then automatically be deleted from the mosquitoes' genetic code after a period of time.
Self-deleting genes to be tested as part of mosquito population control concept
15926B. Hays, UPI, 2020-12-28 18:59:14.
Scientists at Texas A&M have developed a new technique for altering the genes of mosquitoes -- the new technology will cause genetic changes to self-delete from the mosquitoes' genome. Thanks to the breakthrough, described Monday in the Philosophical Transactions of the Royal Society B, researchers can now test-run experimental gene edits without permanently altering a mosquito's genome."People are wary of transgenes spreading in the environment in an uncontrolled manner. We feel that ours is a strategy to potentially prevent that from happening," Zach Adelman, professor of entomology at the Texas A&M College of Agriculture, said in a news release. "The idea is, can we program a transgene to remove itself? Then, the gene won't persist in the environment."
$3.9M project on self-deleting genes takes aim at mosquito-borne diseases
15847O. Kuchment, AGRILIFE Today, 2020-12-28 18:52:03.
To control mosquito populations and prevent them from transmitting diseases such as malaria, many researchers are pursuing strategies in mosquito genetic engineering. A new Texas A&M AgriLife Research project aims to enable temporary “test runs” of proposed genetic changes in mosquitoes, after which the changes remove themselves from the mosquitoes’ genetic code. The project’s first results were published on Dec. 28 in Philosophical Transactions of the Royal Society B, titled “Making gene drive biodegradable.”
Self-deleting genes tested as part of the concept of mosquito population control
15844charlottelarson, NEWYORK NEWS TIMES, 2020-12-28 18:49:28.
Most genetic engineering strategies designed to control mosquito populations, and their ability to spread diseases such as malaria, require gene editing to be combined with gene drives. Gene drives allow altered DNA to spread rapidly throughout the population.
Making gene drive biodegradable
15687J. Zapletal, N. Najmitabrizi, M. Erraguntla, M. A. Lawley, K. M. Myles and Z. N. Adelman, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190804. 2020-12-28 15:02:10.
Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
Mosquito genomes are frequently invaded by transposable elements through horizontal transfer
15371E. S. de Melo and G. L. Wallau, PLOS Genetics, 16:e1008946. 2020-11-30 21:46:36.
We characterized the whole TE content of 24 mosquito genomes and investigated the TE inheritance mode uncovering hundreds of horizontal transfer events among these species and distantly related ones. We also identify a mosquito parasitic filarial worm, th
Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages
15219J. F. Hughes, H. Skaletsky, T. Pyntikova, N. Koutseva, T. Raudsepp, L. G. Brown, D. W. Bellott, T.-J. Cho, S. Dugan-Rocha, Z. Khan, C. Kremitzki, C. Fronick, T. A. Graves-Lindsay, L. Fulton, W. C. Warren, R. K. Wilson, E. Owens, J. E. Womack, W. J. Murphy, Genome Research, 2020-11-18 16:58:55.
Here, we provide evidence that suppression of X–Y crossing-over unleashed a second dynamic: selfish X–Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X–Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X–Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
The bull Y chromosome has evolved to bully its way into gametes
15217Whitehead Institute for Biomedical Research, Phys Org, 2020-11-18 16:54:40.
In a new study, published Nov. 18 in the journal Genome Research, scientists in the lab of Whitehead Institute Member David Page present the first ever full, high-resolution sequence of the Y chromosome of a Hereford bull. The research, more than a decade in the making, suggests that bulls' Y chromosomes have evolved dozens of copies of the same genes in a selfish attempt to make more males—a move that is countered in the female-determining X chromosome. This insight into the forces that govern sex chromosome behavior and evolution will help scientists in Page's lab study genetic differences between males and females and how they play out in health and disease across every part of the body, Page added.
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
Invasion and maintenance of spore killers in populations of ascomycete fungi
15129I. Martinossi-Allibert, C. Veller, S. L. Ament-Velásquez, A. A. Vogan, C. Rueffler and H. Johannesson, bioRxiv, 2020.04.06.026989. 2020-06-30 16:08:48.
We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with the non-driving allele. Our model can be adapted to different fungal life-cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore killing elements, Podospora and Neurospora. We discuss our results in the light of recent empirical findings for these two systems.Competing Interest StatementThe authors have declared no competing interest.
The Enterprise: A massive transposon carrying Spokt meiotic drive genes
15127A. A. Vogan, S. L. Ament-Velásquez, E. Bastiaans, O. Wallerman, S. J. Saupe, A. Suh and H. Johannesson, bioRxiv, 2020.03.25.007153. 2020-04-28 16:03:56.
Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite.
Selfish genes and sexual selection: the impact of genomic parasites on host reproduction
11970N. Wedell, Journal of Zoology, 311:1-12. 2020-04-08 18:18:42.
Selfish genetic elements (SGEs) such as replicating mobile elements, segregation distorters and maternally inherited endosymbionts, bias their transmission success relative to the rest of the genome to increase in representation in subsequent generations. As such, they generate conflict with the rest of the genome. Such intragenomic conflict is also a hallmark of sexually antagonistic (SA) alleles, which are shared genes between the sexes but that have opposing fitness effects when expressed in males and females. However, whilst both SGEs and SA alleles are recognized as common and potent sources of genomic conflict, the realization that SGEs can also generate sexually antagonistic selection and contribute to sexual conflict in addition to generate sexual selection is largely overlooked. Here, I show that SGEs frequently generate sex-specific selection and outline how SGEs that are associated with compromised male fertility can shape female mating patterns, play a key role in the dynamics of sex-determination systems and likely be an important source of sexually antagonistic genetic variation. Given the prevalence of SGEs, their contribution to sexual conflict is likely to be greatly overlooked.
Autosomal suppression and fitness costs of an old driving X chromosome in Drosophila testacea
7363G. Keais, S. Lu and S. Perlman, Journal of Evolutionary Biology, 2020-01-28 21:58:18.
Driving X chromosomes (XDs) are meiotic drivers that bias their own transmission through males by killing Y-bearing gametes. These chromosomes can in theory spread rapidly in populations and cause extinction, but many are found as balanced polymorphisms or as ?cryptic? XDs shut down by drive suppressors. The relative likelihood of these outcomes, as well as the evolutionary pathways through which they come about, are not well-understood. An XD was recently discovered in the mycophagous fly, Drosophila testacea, presenting the opportunity to compare this XD with the well-studied XD of its sister species, Drosophila neotestacea. Comparing features of independently evolved XDs in young sister species is a promising avenue towards understanding how XDs and their counteracting forces change over time. In contrast to the XD of D. neotestacea, we find that the XD of D. testacea is old, with its origin predating the radiation of three species: D. testacea, D. neotestacea, and their shared sister species, Drosophila orientacea. Motivated by the suggestion that older XDs should be more deleterious to carriers, we assessed the effect of the XD on both male and female fertility. Unlike what is known from D. neotestacea, we found a strong fitness cost in females homozygous for the XD in D. testacea: a large proportion of homozygous females failed to produce offspring after being housed with males for several days. Our male fertility experiments show that while XD male fertility is lower under sperm depleting conditions, XD males have comparable fertility to males carrying a standard X chromosome under a free mating regime, which may better approximate conditions in wild populations of D. testacea. Lastly, we demonstrate the presence of autosomal suppression of X chromosome drive. Our results provide support for a model of XD evolution where the dynamics of young XDs are governed by fitness consequences in males, whereas in older XD systems, both suppression and fitness consequences in females likely supersede male fitness costs.
Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements
5602Oberhofer, G., T. Ivy and B. A. Hay, bioRxiv, 2019:2019.2012.2013.876169. 2019-12-17 16:01:29.
Gene drive-based strategies for modifying populations face the problem that genes encoding cargo and the drive mechanism are subject to separation, mutational inactivation, and loss of efficacy. Resilience, an ability to respond to these eventualities in ways that restore population modification with functional genes is needed for long-term success. Here we show that resilience can be achieved through cycles of population modification with Cleave and Rescue (ClvR) selfish genetic elements. ClvR comprises a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage. ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. Cycles of modification can in principal be carried out if two ClvR elements targeting different essential genes are located at the same genomic position, and one of them, ClvRn+1, carries a Rescue transgene from an earlier element, ClvRn. ClvRn+1 should spread within a population of ClvRn, while also bringing about a decrease in its frequency. To test this hypothesis we first show that multiple ClvRs, each targeting a different essential gene, function when located at a common chromosomal position in Drosophila. We then show that when several of these also carry the Rescue from a different ClvR, they spread to transgene fixation in populations fixed for the latter, and at its expense. Therefore, genetic modifications of populations can be overwritten with new content, providing an ongoing point of control.
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.
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.
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.
Evolutionary simulations of Z-linked suppression gene drives
6643L. Holman, Proceedings of the Royal Society B-Biological Sciences, 286:1-9. 2019-10-09 20:23:58.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z-linked 'W-shredders', which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z-linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z-linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W-shredders are likely to be highly effective at eradicating populations provided that resistance to W-shredding cannot evolve. However, W-shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.
Standard deviations: The biological bases of transmission ratio distortion
6179L. Fishman and M. McIntosh, Annual Review of Genetics, 53:347-372. 2019-09-10 18:59:40.
The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms.
Combinations of Spok genes create multiple meiotic drivers in Podospora
7240A. A. Vogan, S. L. Ament-Velásquez, A. Granger-Farbos, J. Svedberg, E. Bastiaans, A. J. M. Debets, V. Coustou, H. Yvanne, C. Clavé, S. J. Saupe and H. Johannesson, eLife, 8:e46454. 2019-07-26 15:53:58.
Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74–167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.
A family of killers
7238M. De Carvalho and S. E. Zanders, eLife, 8:e49211. 2019-07-26 15:50:06.
Spok genes are meiotic drivers that increase their own chances of transmission by killing gametes that do not inherit them.
B chromosome first—mechanisms behind the drive of B chromosomes uncovered
17167Leibniz Institute of Plant Genetics and Crop Plant Research, Phy Org, 2019-06-04 19:27:50.
The specific number of chromosomes is one of the defining characteristics of a species. Whilst the common fruit fly carries 8 chromosomes, the genome of bread wheat counts 42 chromosomes. In comparison, the human genome is made out of a total of 46 chromosomes. However, about 15% of all eukaryotic species additionally carry supernumerary chromosomes referred to as "B chromosomes". Other than the essential chromosomes of the genome, B chromosomes are expendable and often preferentially inherited. This leads to a transmission advantage for B chromosomes called "chromosome drive". To date, little knowledge exists about the mechanisms behind this phenomenon. Researchers from the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben have now been able to decipher the mechanisms behind the drive of B chromosomes in the goatgrass Aegilops speltoides. The novel insights in the workings of chromosome drive were recently published in New Phytologist.
Identification of fk-1;, a Meiotic Driver Undergoing RNA Editing in Neurospora
15131N. A. Rhoades, A. M. Harvey, D. A. Samarajeewa, J. Svedberg, A. Yusifov, A. Abusharekh, P. Manitchotpisit, D. W. Brown, K. J. Sharp, D. G. Rehard, J. Peters, X. Ostolaza-Maldonado, J. Stephenson, P. K. T. Shiu, H. Johannesson and T. M. Hammond, Genetics, 212:93. 2019-05-03 16:12:34.
These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1’s MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.
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.
The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications
3889Beckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019-01-07 00:00:00.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin–antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila
3961Buchman, ABI, Tobin; Marshall, John M.; Akbari, Omar S.; Hay, Bruce A., ACS Synthetic Biology, 7:1359-1370. 2018-01-19 00:00:00.
Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and linked cargo to exceed a high threshold frequency in order for spread to occur are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold frequency required for drive. Reciprocal chromosome translocations were proposed as a tool for bringing about high threshold population replacement in 1940 and 1968. However, translocations able to achieve this goal have only been reported once, in the spider mite Tetranychus urticae, a haplo-diploid species in which there is strong selection in haploid males for fit homozygotes. We report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. These strains drive high threshold population replacement in laboratory populations. While it remains to be shown that engineered translocations can bring about population replacement in wild populations, these observations suggest that further exploration of engineered translocations as a tool for controlled population replacement is warranted.
Genetic villains: Killer meiotic drivers
3959Bravo Núñez, MAN, Nicole L.; Zanders, Sarah E., Trends in Genetics, 34:424-433. 2018-01-17 00:00:00.
Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.
Rapid comeback of males: evolution of male-killer suppression in a green lacewing population
3979Hayashi, MN, M.; Kageyama, D., Proceedings of the Royal Society B-Biological Sciences, 285:6. 2018-01-17 00:00:00.
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi. An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
Selfish genetic elements
3955Agren, JAC, A. G., PLOS Genetics, 14:20. 2018-01-13 00:00:00.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12]
Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly
4024Verspoor Rudi, LSJ, M. L.; Mannion Natasha, L. M.; Hurst Gregory, D. D.; Price Tom, A. R., Evolution Letters, 2:169-179. 2018-01-02 00:00:00.
Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics remain poorly understood. Simple population genetic models predict meiotic drivers will rapidly reach fixation in populations and spread across landscapes. In contrast, natural populations commonly show spatial variation in the frequency of drivers, with drive present in clines or mosaics across species ranges. For example, Drosophila subobscura harbors a sex ratio distorting drive chromosome (SRs) at 15?25% frequency in North Africa, present at less than 2% frequency in adjacent southern Spain, and absent in other European populations. Here, we investigate the forces preventing the spread of the driver northward. We show that SRs has remained at a constant frequency in North Africa, and failed to spread in Spain. We find strong evidence that spread is impeded by genetic incompatibility between SRs and Spanish autosomal backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds we observe strong incompatibilities specific to hybrids bearing SRs. The incompatibilities increase in severity in F2 male hybrids, leading to almost complete infertility. We find no evidence supporting an alternative hypothesis, that there is resistance to drive in Spanish populations. We conclude that the source of the stepped frequency variation is genetic incompatibility between the SRs chromosome and the genetic backgrounds of the adjacent population, preventing SRs spreading northward. The low frequency of SRs in South Spain is consistent with recurrent gene flow across the Strait of Gibraltar combined with selection against the SRs element through genetic incompatibility. This demonstrates that incompatibilities between drive chromosomes and naïve populations can prevent the spread of drive between populations, at a continental scale.
How selfish DNA hijacks its way into egg cells
13516Science, 2017-11-06 13:52:33.
This video was produced by Science magazine and explains and illustrates how gonotaxis or the asymmetrical allocation of chromosomes to developing female gametes occurs in mice. This video reflects an understanding of this process based on the publication by Akera et al (2017).
Spindle asymmetry drives non-Mendelian chromosome segregation
13518T. Akera, L. Chmátal, E. Trimm, K. Yang, C. Aonbangkhen, D. M. Chenoweth, C. Janke, R. M. Schultz and M. A. Lampson, Science, 358:668. 2017-11-03 14:19:19.
Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through a process known as meiotic drive. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle. This implies some asymmetry between the two sides of the spindle, but the molecular mechanisms underlying spindle asymmetry are unknown. Here we found that CDC42 signaling from the cell cortex regulated microtubule tyrosination to induce spindle asymmetry and that non-Mendelian segregation depended on this asymmetry. Cortical CDC42 depends on polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.
A maternal-effect selfish genetic element in Caenorhabditis elegans
14450E. Ben-David, A. Burga and L. Kruglyak, Science, 356:1051. 2017-06-09 17:13:17.
We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans.
Poisons, antidotes, and selfish genes
14448N. Phadnis, Science, 356:1013. 2017-06-09 16:55:51.
On page1051 of this issue, BenDavid et al . (3) chase down a serendipitous observation of an anomaly in genetic crosses to unmask a toxin-antidote type of selfish system in worms.
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.
The Impact of Dissociation on Transposon-Mediated Disease Control Strategies
23831J. M. Marshall, Genetics, 178:1673-1682. 2008-03-01 23:54:22.
Vector-borne diseases such as malaria and dengue fever continue to be a major health concern through much of the world. The emergence of chloroquine-resistant strains of malaria and insecticide-resistant mosquitoes emphasize the need for novel methods of disease control. Recently, there has been much interest in the use of transposable elements to drive resistance genes into vector populations as a means of disease control. One concern that must be addressed before a release is performed is the potential loss of linkage between a transposable element and a resistance gene. Transposable elements such as P and hobo have been shown to produce internal deletion derivatives at a significant rate, and there is concern that a similar process could lead to loss of the resistance gene from the drive system following a transgenic release. Additionally, transposable elements such as Himar1 have been shown to transpose significantly more frequently when free of exogenous DNA. Here, we show that any transposon-mediated gene drive strategy must have an exceptionally low rate of dissociation if it is to be effective. Additionally, the resistance gene must confer a large selective advantage to the vector to surmount the effects of a moderate dissociation rate and transpositional handicap.
Population dynamics of transposable elements: Copy number regulation and species invasion requirements
4282Struchiner, CJK, M. G.; Ribeiro, J. M. C., Journal of Biological Systems, 13:455-475. 2005-01-20 00:00:00.
A deterministic population dynamics model of the spread of transposable elements (TE) in sexually reproducing populations is presented. The population is modeled by a three-parameter equation describing host reproductive capacity, population size and the strength of the density dependence, while TE dynamics were modeled based also on three parameters, the maximum ability of the element to copy itself in the absence of regulation (T(0)), the regulatory effect of copy number decreasing transposition (C(0.5)), and the deleterious effect of each new transposition on host fitness (d). The mechanism of transposition control is therefore a function of the number of new TE copies. Our results indicate that non-regulated elements cannot fix in host populations, and that prediction of stable copy number following successful invasion is mainly a function of the combination of T(0) and C(0.5) values. Fitness reduction does not affect the final copy number after successful invasion of the element. Fitness reduction, however, will affect the surface of the {T(0) x C(0.5)} parameter space leading to successful invasion of the TE. Invasion of host populations by eight or more individuals containing elements with appropriate parameters will lead to successful element fixation at any size of the host population. Host population extinction due to the invasion of TE's is observed in a small area of the {T(0) x C(0.5)} parameter space. These results are qualitatively preserved under alternative choices for the shape of the functions defining regulation of transposition and distinct sets of parameters determining host population dynamics.
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.
Mariner transposition and transformation of the yellow fever mosquito, Aedes aegypti
6256C. J. Coates, N. Jasinskiene, L. Miyashiro and A. A. James, Proceedings of the National Academy of Sciences of the United States of America, 95:3748-3751. 1998-03-07 19:31:51.
The mariner transposable element is capable of interplasmid transposition in the embryonic soma of the yellow fever mosquito, Aedes aegypti. To determine if this demonstrated mobility could be utilized to genetically transform the mosquito, a modified mariner element marked with a wild type allele of the Drosophila melanogaster cinnabar gene was microinjected into embryos of a kynurenine hydroxylase-deficient, white-eyed recipient strain. Three of 69 fertile male founders resulting from the microinjected embryos produced families with colored-eyed progeny individuals, a transformation rate of 4%. The transgene-mediated complementation of eve color was observed to segregate in a Mendelian manner, although one insertion segregates with the recessive allele (female-determining) of the sex-determining locus, and a separate insertion is homozygous lethal. Molecular analysis of selected transformed families demonstrated that a single complete copy of the construct had integrated independently in each case acid that it had done so in a transposase-mediated manner. The availability of a mariner transformation system greatly enhances our ability to study and manipulate this important vector species.
Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly
6254N. Jasinskiene, C. J. Coates, M. Q. Benedict, A. J. Cornel, C. S. Rafferty, A. A. James and F. H. Collins, Proceedings of the National Academy of Sciences of the United States of America, 95:3743-3747. 1998-03-07 19:28:29.
The mosquito Aedes aegypti is the world's most important vector of yellow fever and dengue viruses, Work is currently in progress to control the transmission of these viruses by genetically altering the capacity of wild Ae, aegypti populations to support virus replication. The germ-line transformation system reported here constitutes a major advance toward the implementation of this control strategy, A modified Hermes transposon carrying a 4.7-kb fragment of genomic DNA that includes a wild-type allele of the Drosophila melanogaster cinnabar (cn) gene was used to transform a white-eyed recipient strain of Ae, aegypti. Microinfection of preblastoderm mosquito embryos with this construct resulted in 50% of the emergent G(0) adults showing some color in their eyes, Three transformed families were recovered, each resulting from an independent insertion event of the cn(+)-carrying transposon, The cn(+) gene functioned as a semidominant transgene and segregated in Mendelian ratios, Hermes shows great promise as a vector for efficient, heritable, and stable transformation of this important mosquito vector species.
Selfish DNA and breeding system in flowering plants
4366Burt, AT, R., Proceedings of the Royal Society B-Biological Sciences, 265:141-146. 1998-01-04 00:00:00.
In many species, some individuals carry one or more B chromosomes: extra, or supernumerary chromosomes not part of the normal complement. In most well-studied cases, B's lower the fitness of their carrier and persist in populations only because of accumulation mechanisms analogous to meiotic drive. It has been suggested that such genomic parasites are expected to persist only in outcrossed sexual species, in which uninfected lines of descent can be continuously reinfected; in inbred or asexual species, all selection is between lines of descent, and the genomic parasites are either lost or must evolve into commensals or mutualists. Here we present a simple population genetic model of the effect of outcrossing rate on the frequency of B chromosomes, and find that outcrossing facilitates the spread of parasitic B's, but inhibits the spread of mutualists. Data compiled from the literature on breeding system and B chromosomes of British plants indicate that B's are much more likely to be reported from obligately outcrossed species than inbred species. These results support the ideas that most B chromosomes are parasitic, and that breeding systems play a central role in the biology of selfish genes.
Gene transfer into the Medfly, Ceratitis capitata, using a Drosophila hydei transposable element.
6269T. G. Loukeris, I. Livadaras, B. Arca, S. Zabalou and C. Savakis, Science, 270:2002-2005. 1995-12-22 16:35:47.
Exogenous functional DNA was introduced into the germline chromosomes of the Mediterranean fruit fly (medfly) Ceratitis capitata with a germline transformation system based on the transposable element Minos from Drosophila hydei. Transformants were identified as phenotypic revertants of a white-eyed mutation carried by the recipient strain. Clusters of transformants were detected among the progeny of 390 individuals screened for germline transformation. Five independent and phenotypically active integration events were identified, in each of which a single copy of the transposon was inserted into a different site of the medfly genome. Molecular analysis indicates that they represent transposase-mediated insertions of the transposon into medfly chromosomes.
Rapid spread of transposable P elements in experimental populations of Drosophila melanogaster.
6265A. G. Good, G. A. Meister, H. W. Brock, T. A. Grigliatti and D. A. Hickey, Genetics, 1223:387-396. 1989-05-08 16:20:58.
The invasion of P elements in natural populations of Drosophila melanogaster was modeled by establishing laboratory populations with 1 %, 5% and 10% P genomes and monitoring the populations for 20 generations. In one experiment, the ability of flies to either induce or suppress gonadal sterility in different generations was correlated with the amount of P element DNA. In a second experiment, the percentage of genomes that contained P elements, and the distribution of P elements among individual flies was monitored. The ability to induce gonadal dysgenesis increased rapidly each generation. However, the increase in P cytotype lagged behind by five to ten generations. The total amount of P element DNA and the frequency of flies containing P elements increased each generation. The number of P elements within individual genomes decreased initially, but then increased. Finally, the distribution of P elements within the genomes of individuals from later generations varied considerably, and this pattern differed from the parental P strain. These results suggest that the interaction between the assortment and recombination of chromosomal segments, and multiplicative transposition could result in the rapid spread of P elements in natural populations
Genetic-transformation of Drosophila with transposable element vectors
6252G. M. Rubin and A. C. Spradling, Science, 218:348-353. 1982-10-22 19:25:36.
Exogenous DNA sequences were introduced into the Drosophila germ line. A rosy transposon (ry1), constructed by inserting a chromosomal DNA fragment containing the wild-type rosy gene into a P transposable element, transformed germ line cells in 20 to 50 percent of the injected rosy mutant embryos. Transformants contained one or two copies of chromosomally integrated, intact ry1 that were stably inherited in subsequent generations. These transformed flies had wild-type eye color indicating that the visible genetic defect in the host strain could be fully and permanently corrected by the transferred gene. To demonstrate the generality of this approach, a DNA segment that does not confer a recognizable phenotype on recipients was also transferred into germ line chromosomes.
Mutable loci in maize.
6388B. McClintock, Carnegie Inst. Washington Year Book, 47:155-169. 1948-02-10 16:25:33.
Previous reports have state that the number of unstable loci have recently arisen in maize culture. In a particular cell of a plant, a normal "wild-type" locus becomes altered; the normal, dominant expression of this locus changes and gives rise to a recessive expression (or, in several cases, a recessive locus become unstable and mutates toward a dominant expression). This expression of the locus need not be permanent. In some decendent cells, a second change may occur within the locus that results in the restoring of the capacity of thelocus to express the dominant phenotype or brings about an intermediate expression between full recessive and full dominant. In the latter case, a third alteration may occur in some decendent cells that steps up the phenotype expression toward the full dominant or reduces it toward the full recessive.
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