Predoctoral Researcher, Stowers Institute for Medical Research
Exploring meiotic drive and genetic conflict, an example of an infertility causing mechanism
A gene found in fission yeast, wtf4, acts as both a poison and an antidote to ensure its transmission into the next generation. wtf4 destroys developing gametes (analogous to sperm) that don't posses it. The gene poisons all gametes, but keeps the antidote only for itself. In that way, the gene kills any gametes that don't inherit it, drastically reducing fertility. Successful completion of this research will provide a vital tool for exploring these types of selfish genes, becoming a textbook example of a mechanism of infertility.
Abstract: A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
Pub.: 18 Feb '16, Pinned: 07 Aug '17
Abstract: Supernumerary chromosomes have been studied in many species of eukaryotes, including the cichlid fish, Astatotilapia latifasciata. However, there are many unanswered questions about the maintenance, inheritance, and functional aspects of supernumerary chromosomes. The cichlid family has been highlighted as a model for evolutionary studies, including those that focus on mechanisms of chromosome evolution. Individuals of A. latifasciata are known to carry up to two B heterochromatic isochromosomes that are enriched in repetitive DNA and contain few intact gene sequences. We isolated and characterized a transcriptionally active repeated DNA, called B chromosome noncoding DNA (BncDNA), highly represented across all B chromosomes of A. latifasciata. BncDNA transcripts are differentially processed among six different tissues, including the production of smaller transcripts, indicating transcriptional variation may be linked to B chromosome presence and sexual phenotype. The transcript lengths and lack of similarity with known protein/gene sequences indicate BncRNA might represent a novel long noncoding RNA family (lncRNA). The potential for interaction between BncRNA and known miRNAs were computationally predicted, resulting in the identification of possible binding of this sequence in upregulated miRNAs related to the presence of B chromosomes. In conclusion, Bnc is a transcriptionally active repetitive DNA enriched in B chromosomes with potential action over B chromosome maintenance in somatic cells and meiotic drive in gametic cells.
Pub.: 14 May '16, Pinned: 07 Aug '17
Abstract: When there is no recombination (achiasmy) in one sex, it is in the heterogametic one. This observation is so consistent that it constitutes one of the few patterns in biology that may be regarded as a 'rule' and Haldane (Haldane 1922 J. Genet. 12, 101-109. (doi:10.1007/BF02983075)) proposed that it might be driven by selection against recombination in the sex chromosomes. Yet differences in recombination rates between the sexes (heterochiasmy) have also been reported in hermaphroditic species that lack sex chromosomes. In plants-the vast majority of which are hermaphroditic-selection at the haploid stage has been proposed to drive heterochiasmy. Yet few data are available for hermaphroditic animals, and barely any for hermaphroditic vertebrates. Here, we leverage reciprocal crosses between two black hamlets (Hypoplectrus nigricans, Serranidae), simultaneously hermaphroditic reef fishes from the wider Caribbean, to generate high-density egg- and sperm-specific linkage maps for each parent. We find globally higher recombination rates in the eggs, with dramatically pronounced heterochiasmy at the chromosome peripheries. We suggest that this pattern may be due to female meiotic drive, and that this process may be an important source of heterochiasmy in animals. We also identify a large non-recombining region that may play a role in speciation and local adaptation in Hypoplectrus.
Pub.: 16 Dec '16, Pinned: 07 Aug '17
Abstract: Comparative Cytogenetics 11(2): 375-392 DOI: 10.3897/compcytogen.v11i2.11779 Authors: Manoj K. Dhar, Gurmeet Kour, Sanjana Kaul Abstract: Plantago lagopus is a diploid (2n = 2x =12) weed belonging to family Plantaginaceae. We reported a novel B chromosome in this species composed of 5S and 45S ribosomal DNA and other repetitive elements. In the present work, presence of B chromosome(s) was confirmed through FISH on root tip and pollen mother cells. Several experiments were done to determine the transmission of B chromosome through male and female sex tracks. Progenies derived from the reciprocal crosses between plants with (1B) and without (0B) B chromosomes were studied. The frequency of B chromosome bearing plants was significantly higher than expected, in the progeny of 1B female × 0B male. Thus, the B chromosome seems to have preferential transmission through the female sex track, which may be due to meiotic drive. One of the most intriguing aspects of the present study was the recovery of plants having more chromosomes than the standard complement of 12 chromosomes. Such plants were isolated from the progenies of B chromosome carrying plants. The origin of these plants can be explained on the basis of a two step process; formation of unreduced gametes in 1B plants and fusion of unreduced gametes with the normal gametes or other unreduced gametes. Several molecular techniques were used which unequivocally confirmed similar genetic constitution of 1B (parent) and plants with higher number of chromosomes. HTML XML PDF
Pub.: 22 May '17, Pinned: 07 Aug '17
Abstract: The connection between selfish genes and selfish goals is not merely metaphorical. Many goals that shape contemporary cognition and behavior are psychological products of evolutionarily fundamental motivational systems and thus are phenotypic manifestations of genes. An evolutionary perspective can add depth and nuance to our understanding of "selfish goals" and their implications for human cognition and behavior.
Pub.: 30 Apr '14, Pinned: 07 Aug '17
Abstract: Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical basis a gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions.
Pub.: 14 Apr '15, Pinned: 07 Aug '17
Abstract: Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing--in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact--which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.
Pub.: 09 Nov '04, Pinned: 30 Jun '17
Abstract: Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae, demonstrating that these genetic elements are not necessarily benign but maybe parasitic. We estimate a selective load of approximately 1-2% in 'natural' niches. The second aspect we examine is the ability of HEGs to affect hosts' sexual behaviour. As all selfish genes critically rely on sex for spread, then any selfish gene correlated with increased host sexuality will enjoy a transmission advantage. While classic parasites are known to manipulate host behaviour, we are not aware of any evidence showing a selfish gene is capable of affecting host promiscuity. The data presented here show a selfish element may increase the propensity of its eukaryote host to undergo sex and along with increased rates of non-Mendelian inheritance, this may counterbalance mitotic selective load and promote spread. Demonstration that selfish genes are correlated with increased promiscuity in eukaryotes connects with ideas suggesting that selfish genes promoted the evolution of sex initially.
Pub.: 21 Sep '13, Pinned: 30 Jun '17
Abstract: Selfish genes are DNA elements that increase their rate of genetic transmission at the expense of other genes in the genome and can therefore quickly spread within a population. It has been suggested that selfish elements could be exploited to modify the genome of entire populations for medical and ecological applications. Here we report that transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) can be engineered into site-specific synthetic selfish elements (SSEs) and demonstrate their transmission of up to 70% in the Drosophila germline. We show here that SSEs can spread via DNA break-induced homologous recombination, a process known as 'homing' similar to that observed for homing endonuclease genes (HEGs), despite their fundamentally different modes of DNA binding and cleavage. We observed that TALEN and ZFN have a reduced capability of secondary homing compared to HEG as their repetitive structure had a negative effect on their genetic stability. The modular architecture of ZFNs and TALENs allows for the rapid design of novel SSEs against specific genomic sequences making them potentially suitable for the genetic engineering of wild-type populations of animals and plants, in applications such as gene replacement or population suppression of pest species.
Pub.: 08 May '14, Pinned: 30 Jun '17
Abstract: Supernumerary B chromosomes (Bs) are a major source of intraspecific variation in nuclear DNA amounts in numerous species of plants. They favour large genomes, and create polymorphisms for DNA variation in natural populations. By studying Bs we can gain useful knowledge about the organization, function and evolution of genomes. There are also significant biological questions concerning the origin and structural organization of Bs, and the way in which these selfish elements can establish themselves by exploiting the replicative machinery of their host genome nucleus.It is a sine qua non that Bs originate from the A chromosomes, in a variety of ways. We can study their modes of drive and ask how it is that chromosomes which apparently lack genes can have control over their own drive process which leads to their survival in natural populations. Molecular cytogenetic studies are opening up new avenues of investigation. Population equilibria for B frequencies are determined by a balance between accumulation and harmful effects. Bs are also subject to meiotic loss due to polysomy and to elimination at meiosis as univalents. These balancing forces can be seen in the context of host/parasite interaction, based on a dissection of the genetic elements in both As and Bs (in maize) which interact to bring about a stable equilibrium, at least for a snapshot in time.Aside from their intrinsic enigmatic properties, B chromosomes make useful experimental tools to study genome organization. Thus far they have not been exploited for their applications, other than through the use of A-B translocations used for gene mapping in maize; but there are opportunities to use them to modulate the frequency and distribution of recombination, to diploidize allopolyploids, to study centromeres and to be developed as plant artificial chromosomes; given that they can be structurally modified and their inheritance stabilized.
Pub.: 21 Aug '07, Pinned: 30 Jun '17
Abstract: Segregation distorters located on sex chromosomes are predicted to sweep to fixation and cause extinction via a shortage of one sex, but in nature they are often found at low, stable frequencies. One potential resolution to this longstanding puzzle involves female multiple mating (polyandry). Because many meiotic drivers severely reduce the sperm competitive ability of their male carriers, females are predicted to evolve more frequent polyandry and thereby promote sperm competition when a meiotic driver invades. Consequently, the driving chromosome's relative fitness should decline, halting or reversing its spread. We used formal modeling to show that this initially appealing hypothesis cannot resolve the puzzle alone: other selective pressures (e.g., low fitness of drive homozygotes) are required to establish a stable meiotic drive polymorphism. However, polyandry and meiotic drive can strongly affect one another's frequency, and polyandrous populations may be resistant to the invasion of rare drive mutants.
Pub.: 08 Jan '15, Pinned: 30 Jun '17
Abstract: Meiotic drive elements are a special class of evolutionarily "selfish genes" that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
Pub.: 02 Apr '15, Pinned: 30 Jun '17
Abstract: Like several other species of Drosophila, D. quinaria is polymorphic for X-chromosome meiotic drive; matings involving males that carry a "sex-ratio" X chromosome (X(SR) ) result in the production of strongly female-biased offspring sex ratios (Jaenike 1996). A survey of isofemale lines of D. quinaria from several populations reveals that there is genetic variation for partial suppression of this meiotic drive. Crossing experiments show that there is Y-linked, and probably autosomal, variation for suppression of drive. Y-linked suppressors of X-chromosome drive have now been described in several species of Diptera. I develop a simple model for the maintenance of Y-chromosome polymorphism in species polymorphic for X-linked meiotic drive. One interesting feature of this model is that, if there is a stable Y-chromosome polymorphism, then the equilibrium frequency of the standard and sex-ratio X chromosomes is determined solely by Y-chromosome parameters, not by the fitness effects of the different X chromosomes on their carriers. This model suggests that Y-chromosome polymorphism may be easier to maintain than previously thought, and I hypothesize that karyotypic variation in Y chromosomes will be found to be associated with suppression of sex-ratio meiotic drive in other species of Drosophila.
Pub.: 01 Feb '99, Pinned: 30 Jun '17
Abstract: Selfish genes that bias their own transmission during meiosis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes have important evolutionary and ecological consequences, and can be found in a broad range of taxa including plants, mammals, and insects. Here we report a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. We show that males carrying the driving X (SR males) sire 80-100% female offspring, and possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. We find that the majority of sons produced by SR males are sterile and appear to lack a Y chromosome, suggesting that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. By screening wild-caught flies using progeny sex ratios and a diagnostic marker, we demonstrate that the driving X is present in wild populations at a frequency of ~10% and that suppressors of drive are segregating in the same population. The testacea species group appears to be a hotspot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves. This article is protected by copyright. All rights reserved.
Pub.: 13 Apr '17, Pinned: 30 Jun '17
Abstract: The fission yeast Schizosaccharomyces pombe is especially well suited for studying meiosis in molecular detail. Experiments with S. pombe strains that undergo a nearly synchronous meiosis-at variable temperatures-have elucidated the mechanisms of meiotic progression and the proteins that are involved. For example, studies focused on the initiation of meiotic recombination by programmed DNA double-strand breaks (DSBs) have proven exceptionally informative. In meiosis, some regions of DNA have more frequent DSBs than the surrounding regions. These DSB hotspots can be visualized by Southern blot hybridization of restriction fragments ranging from kilobases (kb) to megabases (Mb) in size. More recently, the benefits of genome-wide analysis to map the distribution and frequency of meiotic DSBs have been attained, with resolution down to the nucleotide level. Infrequent, non-hotspot DSBs previously not detectable have been observed, creating a better understanding of how recombination is regulated. Additional genome-wide analyses have shown proteins that bind specifically to DSB hotspots, providing insight into how the DSB initiation complex functions. We describe here detailed methods for achieving these results.
Pub.: 30 Mar '17, Pinned: 30 Jun '17
Abstract: The fission yeast Schizosaccharomyces pombe lacks a diverse toolkit of inducible promoters for experimental manipulation. Available inducible promoters suffer from slow induction kinetics, limited control of expression levels and/or a requirement for defined growth medium. In particular, no S. pombe inducible promoter systems exhibit a linear dose response, which would allow expression to be tuned to specific levels. We have adapted a fast, orthogonal promoter system with a large dynamic range and a linear dose response, based on β-estradiol-regulated function of the human estrogen receptor, for use in S. pombe. We show that this promoter system, termed Z3 EV, turns on quickly, can reach a maximal induction of 20 fold, and exhibits a linear dose response over its entire induction range, with few off target effects. We demonstrate the utility of this system by regulating the mitotic inhibitor Wee1 to create a strain in which cell size is regulated by β-estradiol concentration. This promoter system will be of great utility for experimentally regulating gene expression in fission yeast.
Pub.: 20 Apr '17, Pinned: 30 Jun '17
Abstract: Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve.
Pub.: 21 Jun '17, Pinned: 30 Jun '17
Abstract: The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such ‘symmetric’ PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation.
Pub.: 03 Feb '16, Pinned: 30 Jun '17
Abstract: Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.
Pub.: 28 Feb '16, Pinned: 30 Jun '17
Abstract: Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans. Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.
Pub.: 15 Mar '16, Pinned: 30 Jun '17
Abstract: Sexual antagonism and meiotic drive are sex‐specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male‐beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz′, which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome.
Pub.: 04 Apr '16, Pinned: 30 Jun '17
Abstract: It has long been known that processes occurring within a species may impact the interactions between species. For example, as competitive ability is sensitive to parameters including reproductive rate, carrying capacity and competition efficiency, the outcome of interspecific competition may be influenced by any process that alters these attributes. Although several such scenarios have been discussed, the influence of selfish genetic elements within one species on competition between species has not received theoretical treatment. We show that, with strong competition, sex-ratio meiotic drive systems can result in a significant shift in community composition because the effective birth rate in the population may be increased by a female-biased sex ratio. Using empirical data, we attempt to estimate the magnitude of this effect in several Drosophila species. We infer that meiotic drive elements, selfish genetic elements within species, can provide a substantial competitive advantage to that species within a community.
Pub.: 20 May '14, Pinned: 30 Jun '17
Abstract: Maternally inherited Wolbachia endosymbionts manipulate arthropod reproduction in various ways. In the butterfly Eurema mandarina, a cytoplasmic incompatibility-inducing Wolbachia strain wCI and the associated mtDNA haplotypes are known to originate from the sister species Eurema hecabe, which offered a good case study for microbe-mediated hybrid introgression. Besides wCI, some females with the Z0 karyotype harbour a distinct Wolbachia strain wFem, which causes all-female production by meiotic drive and feminization. We report that a considerable proportion of E. mandarina females (65.7%) were infected with both wCI and wFem (CF) on Tanegashima Island. While females singly infected with wCI (C) produced offspring at a 1 : 1 sex ratio, CF females produced only females. Although Z-linked sequence polymorphism showed no signs of divergence between C and CF females, mtDNA split into two discrete clades; one consisted of C females and the other CF females, both of which formed a clade with E. hecabe but not with uninfected E. mandarina This suggests that CF matrilines also, but independently, experienced a selective sweep after hybrid introgression from E. hecabe Distinct evolutionary forces were suggested to have caused C and CF matrilines to diverge, which would be irreversible because of the particular phenotype of wFem.
Pub.: 02 Jun '17, Pinned: 30 Jun '17
Abstract: Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide of single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an ~8% increase in transmission frequency, corresponding to a ~54:46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of F1 progeny.
Pub.: 05 Mar '17, Pinned: 30 Jun '17
Abstract: Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) × Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) × Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102-kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hypervariable regions, the longest of which includes SKC1 The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.
Pub.: 19 Jun '16, Pinned: 28 Jun '17
Abstract: 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.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.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.
Pub.: 23 Jun '16, Pinned: 28 Jun '17
Abstract: RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for the Cas9 scalpel.
Pub.: 14 Jan '17, Pinned: 28 Jun '17
Abstract: Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility.
Pub.: 21 Jun '17, Pinned: 28 Jun '17