Autosomal suppression and fitness costs of an old driving X chromosome in Drosophila testacea

Driving X chromosomes (X^Ds) 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” X^Ds shut down by drive suppressors. The relative likelihood of these outcomes and the evolutionary pathways through which they come about are not well understood. An X^D was recently discovered in the mycophagous fly, Drosophila testacea, presenting the opportunity to compare this X^D with the well‐studied X^D of its sister species, Drosophila neotestacea. Comparing features of independently evolved X^Ds in young sister species is a promising avenue towards understanding how X^Ds and their counteracting forces change over time. In contrast to the X^D of D. neotestacea, we find that the X^D 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 X^Ds should be more deleterious to carriers, we assessed the effect of the X^D on both male and female fertility. Unlike what is known from D. neotestacea, we found a strong fitness cost in females homozygous for the X^D 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 although X^D male fertility is lower under sperm‐depleting conditions, X^D 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 X^D evolution where the dynamics of young X^Ds are governed by fitness consequences in males, whereas in older X^D systems, both suppression and fitness consequences in females likely supersede male fitness costs.     

Unravelling the mystery of female meiotic drive: where we are

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.     

Local selection underlies the geographic distribution of sex-ratio drive in Drosophila neotestacea

"Selfish" genetic elements promote their own transmission to the next generation, often at a cost to the host individual. A sex-ratio (SR) driving X chromosome prevents the maturation of Y-bearing sperm, and as a result is transmitted to 100% of the offspring, all of which are female. Because the spread of a SR chromosome can result in a female-biased population sex ratio, the ecological and evolutionary consequences of harboring this selfish element can be severe. In this study, we show that the prevalence of SR drive in Drosophila neotestacea varies between 0% and 30% among populations, and is common in the south whereas rare in the north. The prevalence of SR is not associated with the presence of suppressors of drive, geographic distance, or genetic distance based on autosomal microsatellite loci. Instead, our results indicate that ecological selection on SR drive varies among populations, as the prevalence of SR is highly correlated with climatic factors, with the severity of winter the best determinant of SR frequency. Thus, ecological and demographic factors may have significant consequences for the short and long term evolutionary dynamics of selfish elements and the manner with which they coevolve with the rest of the genome.     

Association of polyandry and sex-ratio drive prevalence in natural populations of Drosophila neotestacea

Selfish genetic elements bias their own transmission to the next generation, even at the expense of the fitness of their carrier. Sex-ratio (SR) meiotic drive occurs when an X-chromosome causes Y-bearing sperm to die during male spermatogenesis, so that it is passed on to all of the male''s offspring, which are all daughters. How SR is maintained as a stable polymorphism in the absence of genetic suppressors of drive is unknown. Here, we investigate the potential for the female remating rate to affect SR dynamics in natural populations, using the fly Drosophila neotestacea. In controlled laboratory conditions, females from populations where SR is rare mate more often than females from populations where SR is common. Furthermore, only when males mate multiply does the average fertility of SR males relative to wild-type males decrease to a level that can prevent SR from spreading. Our results suggest that differences in the female mating rate among populations may contribute to SR dynamics in the wild, and thus also affect the outcome of this intragenomic conflict. In line with this, we also present evidence of a localized population crash due to SR that may have resulted from habitat fragmentation along with a reduced mating rate.     

Origin,evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster

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.     

A prezygotic transmission distorter acting equally in female and male zebra finches Taeniopygia guttata

The two parental alleles at a specific locus are usually inherited with equal probability to the offspring. However, at least three processes can lead to an apparent departure from fair segregation: early viability selection, biased gene conversion and various kinds of segregation distortion. Here, we conduct a genome‐wide scan for transmission distortion in a captive population of zebra finches (Taeniopygia guttata) using 1302 single‐nucleotide polymorphisms (SNPs) followed by confirmatory analyses on independent samples from the same population. In the initial genome‐wide scan, we found significant distortion at three linked loci on chromosome Tgu2 and we were able to replicate this finding in each of two follow‐up data sets [overall transmission ratio = 0.567 (95% CI = 0.536–0.600), based on 1101 informative meioses]. Although the driving allele was preferentially transmitted by both heterozygous females [ratio = 0.560 (95% CI = 0.519–0.603)] and heterozygous males [ratio = 0.575 (95% CI = 0.531–0.623)], we could rule out postzygotic viability selection and biased gene conversion as possible mechanisms. Early postzygotic viability selection is unlikely, because it would result in eggs with no visible embryo and hence no opportunity for genotyping, and we confirmed that both females and males heterozygous for the driving allele did not produce a larger proportion of such eggs than homozygous birds. Biased gene conversion is expected to be rather localized, while we could trace transmission distortion in haplotypes of several megabases in a recombination desert. Thus, we here report the rare case of a prezygotically active transmission distorter operating equally effectively in female and male meioses.     

B chromosomes reveal a female meiotic drive suppression system in Drosophila melanogaster

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Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni

Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of XSR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that XSR/XST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.     

The Y chromosomes of Drosophila simulans are highly polymorphic for their ability to suppress sex-ratio drive

The sex-ratio trait, known in several species of Drosophila including D. simulans, results from meiotic drive of the X chromosome against the Y. Males that carry a sex-ratio X chromosome produce strongly female-biased progeny. In D. simulans, drive suppressors have evolved on the Y chromosome and on the autosomes. Both the frequency of sex-ratio X and the strength of the total drive suppression (Y-linked and autosomal) vary widely among geographic populations of this worldwide species. We have investigated the pattern of Y-linked drive suppression in six natural populations representative of this variability. Y-linked suppressors were found to be a regular component of the suppression, with large differences between populations in the mean level of suppression. These variations did not correspond to differences in frequency of discrete types of Y chromosomes, but to a more or less wide continuum of phenotypes, from nonsuppressor to partial or total suppressor. We concluded that a large diversity of Y-linked suppressor alleles exists in D. simulans and that some populations are highly polymorphic. Our results support the hypothesis that a Y-chromosome polymorphism can be easily maintained by a balance between meiotic drive and the cost of drive suppression.     

X-linked meiotic drive can boost population size and persistence

X-linked meiotic drivers cause X-bearing sperm to be produced in excess by male carriers, leading to female-biased sex ratios. 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.     

Selective sweeps in a 2-locus model for sex-ratio meiotic drive in Drosophila simulans

A way to identify loci subject to positive selection is to detect the signature of selective sweeps in given chromosomal regions. It is revealed by the departure of DNA polymorphism patterns from the neutral equilibrium predicted by coalescent theory. We surveyed DNA sequence variation in a region formerly identified as causing "sex-ratio" meiotic drive in Drosophila simulans. We found evidence that this system evolved by positive selection at 2 neighboring loci, which thus appear to be required simultaneously for meiotic drive to occur. The 2 regions are approximately 150-kb distant, corresponding to a genetic distance of 0.1 cM. The presumably large transmission advantage of chromosomes carrying meiotic drive alleles at both loci has not erased the individual signature of selection at each locus. This chromosome fragment combines a high level of linkage disequilibrium between the 2 critical regions with a high recombination rate. As a result, 2 characteristic traits of selective sweeps--the reduction of variation and the departure from selective neutrality in haplotype tests--show a bimodal pattern. Linkage disequilibrium level indicates that, in the natural population from Madagascar used in this study, the selective sweep may be as recent as 100 years.     

Parallel pathways for recruiting effector proteins determine centromere drive and suppression

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Sex ratio distorter reduces sperm competitive ability in an insect

Selfish genetic elements (SGEs) are ubiquitous in animals and often associated with low male fertility due to reduced sperm number in male carriers. In the fruit fly Drosophila pseudoobscura , the meiotic driving X chromosome "sex ratio" kills Y-bearing sperm in carrier males (SR males), resulting in female only broods. We competed SR males against the ejaculates of noncarrying standard males (ST males), and quantified the number of sperm transferred by SR and ST males to females. We show that SR males are very poor sperm competitors, which is partly related to transfer of fewer sperm during mating. However, sperm numbers alone cannot explain the observed paternity reduction, indicating SR males' sperm may be of reduced quality, possibly due to damage during the killing of the noncarrying Y-sperm. The reduction in sperm competitive ability due to SR is large enough to potentially stabilize the spread of sex ratio drive through populations. The poor sperm competitive ability of SR males coupled with their low fitness as mates could favor increased remating by females to reduce paternity by SR males. Given the generally poor performance of SGE-carrying males in sperm competition, this may generate strong selective pressure favoring polyandry in many species.     

Occasional recombination of a selfish X‐chromosome may permit its persistence at high frequencies in the wild

The sex‐ratio X‐chromosome (SR) is a selfish chromosome that promotes its own transmission to the next generation by destroying Y‐bearing sperm in the testes of carrier males. In some natural populations of the fly Drosophila neotestacea, up to 30% of the X‐chromosomes are SR chromosomes. To investigate the molecular evolutionary history and consequences of SR, we sequenced SR and standard (ST) males at 11 X‐linked loci that span the ST X‐chromosome and at seven arbitrarily chosen autosomal loci from a sample of D. neotestacea males from throughout the species range. We found that the evolutionary relationship between ST and SR varies among individual markers, but genetic differentiation between SR and ST is chromosome‐wide and likely due to large chromosomal inversions that suppress recombination. However, SR does not consist of a single multilocus haplotype: we find evidence for gene flow between ST and SR at every locus assayed. Furthermore, we do not find long‐distance linkage disequilibrium within SR chromosomes, suggesting that recombination occurs in females homozygous for SR. Finally, polymorphism on SR is reduced compared to that on ST, and loci displaying signatures of selection on ST do not show similar patterns on SR. Thus, even if selection is less effective on SR, our results suggest that gene flow with ST and recombination between SR chromosomes may prevent the accumulation of deleterious mutations and allow its long‐term persistence at relatively high frequencies.     

The Selfish Segregation Distorter Gene Complex of Drosophila melanogaster

Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD(+) spermatids so that SD/SD(+) males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci-the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)-and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.     

An X chromosome locus in Drosophila melanogaster that enhances survival of the triplo-lethal genotype,Dp-(Tpl)

Only a single locus (Tpl) is known in the Drosophila melanogaster genome that leads to early lethality when present as a heterozygous duplication (three doses) or deficiency (one dose). We report the recovery of third instar larvae (and of occasional adults) carrying a duplication for the triplo-lethal locus, Dp(Tpl). Karyotype analysis of the larvae showed that the individuals surviving were almost entirely 3X;2A metafemales. We examined the question of whether the entire X or a single X locus was a major factor permitting survival. X-Y translocations were used to produce females hyperploid for different portions of the X and carrying Dp(Tpl). Analysis of metaphase chromosomes by quinacrine fluorescence pattern indicates that the X chromosome region between 6D and 7DE must be present in an extra copy to enhance the survival of Tpl duplication-bearing females. Another type of experiment suggests that it is the region between 7C and 7DE which is essential.     

Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus

Most meiotic drivers, such as the t‐haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex‐specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture.     

The meiotic drive system on maize abnormal chromosome 10 contains few essential genes

In maize, a distal portion of abnormal chromosome 10 (Ab10) causes the meiotic drive of itself as well as many unlinked heterochromatic regions known as knobs. The Ab10 drive system, which encodes trans- as well as cis-acting components, occupies a large region of chromosome 10L equivalent to 3% of the genome. Here we describe five new structural mutations of Ab10 (five deletions and a duplication) that arose from a screen for meiotic drive mutants. The high frequency of breakage events, detected both genetically and cytologically, suggest that the chromosome may be especially unstable. Very large deletions within the drive system are female-transmissible and plants homozygous for deficiencies lacking much of this interval can be grown to maturity. The data suggest that few genes required for normal growth and development lie within the portion of Ab10 responsible for meiotic drive. These and other published data suggest that meiotic drive systems tend to evolve in gene-sparse or otherwise information-poor regions of the genome where they are less likely to negatively affect individual fitness.     

Sex-ratio distortion in Drosophila simulans: co-occurence of a meiotic drive and a suppressor of drive

A sex-ratio distortion factor was found at high frequency in D. simulans strains from Seychelles and New Caledonia. This factor is poorly or not expressed within those strains which are resistant to it. Its presence was detected by crossing females from New Caledonia or the Seychelles with males from a different geographic origin. Most of the F1 males obtained produced an excess of females (up to 99%) in their progeny. The two strains are infected with Wolbachia, but these micro-organisms are not involved in the sex-ratio distortion. The sex-ratio factor is shown to be an X-linked meiotic driver; nuclear resistance factor(s) act by suppressing the drive. It is likely that the same X-located driver invaded the two populations, which subsequently developed resistance factor(s) against it.     

The evolution of autosomal suppressors of sex-ratio drive in Drosophila simulans

Sex-ratio drive, which results in males siring female-biased progeny, has been reported in several Drosophila species, including D. simulans. It is caused by X-linked drivers that prevent the production of Y-bearing sperm. In natural populations of D. simulans, the drivers are usually cryptic, because their spread has elicited the evolution of drive suppressors. We investigated autosomal suppression in flies from Madagascar, Réunion and Kenya. Autosomal suppressors were found in all three places, indicating that they are a regular component of drive suppression over this geographic area, where strong Y-linked suppressors also occur. These suppressors were suspected of being polymorphic in Madagascar and Réunion and proved to be polymorphic in Kenya. We developed a model simulating the evolution of neutral autosomal suppressors in order to explore the effects of the number of suppressor genes, their relative strength and the co-occurrence of Y-linked suppressors. The most interesting prediction of the model is that when suppression is multigenic, suppressor loci can remain polymorphic despite the absence of balancing selection if an equal sex-ratio is restored in the population before the suppressor alleles become fixed at all loci. The model also emphasises the importance of the sterility of distorters sons in suppressor dynamics.