Factors of maintaining chromosome polymorphism in common vole Microtus arvalis pallas, 1779: Reduced fertility and meiotic drive

The common vole Microtus arvalis (the form obscurus) exhibits polymorphism of a pericentric inversion in chromosome pair 5 throughout the species range. In the Urals populations, the frequency of an acrocentric variant of the heteromorphic chromosome is very low (on average 3.2%) and virtually does not change annually. The factors of maintaining stable chromosomal polymorphism in the common vole were studied under conditions of a laboratory colony. Heterozygous and homozygous for the acrocentric chromosome females showed a significant reduction of the reproductive output irrespective of the male karyotype. This effect was manifested mostly in litter size at birth. A number of cytogenetic and exophenotypic characteristics, as well as parent-offspring transmission of this chromosome in crosses of various types, were examined. We have found meiotic drive in favor of the acrocentric, as a result of which the frequency of the acrocentric (without taking into account the postnatal mortality) totaled over all cross variants (0.48) was significantly higher than that expected with random segregation (0.42). It is likely that meiotic drive of the acrocentric largely compensates for the reduced fertility of its carriers, being among the factors of maintaining it in natural populations.     

Meiotic drive favors Robertsonian metacentric chromosomes in the common shrew (Sorex araneus, Insectivora, mammalia)

Meiotic drive has attracted much interest because it concerns the robustness of Mendelian segregation and its genetic and evolutionary stability. We studied chromosomal meiotic drive in the common shrew (Sorex araneus, Insectivora, Mammalia), which exhibits one of the most remarkable chromosomal polymorphisms within mammalian species. The open question of the evolutionary success of metacentric chromosomes (Robertsonian fusions) versus acrocentrics in the common shrew prompted us to test whether a segregation distortion in favor of metacentrics is present in female and/or male meiosis. Performing crosses under controlled laboratory conditions with animals from natural populations, we found a clear trend toward a segregation distortion in favor of metacentrics during male meiosis, two chromosome combinations (gm and jl) being significantly preferred over their acrocentric homologs. Apart for one Robertsonian fusion (hi), this trend was absent in female meiosis. We propose a model based on recombination events between twin acrocentrics to explain the difference in transmission ratios of the same metacentric in different sexes and unequal drive of particular metacentrics in the same sex. Pooled data for female and male meiosis revealed a trend toward stronger segregation distortion for larger metacentrics. This is partially in agreement with the frequency of metacentrics occurring in natural populations of a chromosome race showing a high degree of chromosomal polymorphism.     

Pericentric inversion in natural populations of Oligoryzomys nigripes (Rodentia: Sigmodontinae).

We analysed polymorphism for pericentric inversion in chromosome 3 of Oligoryzomys nigripes (Rodentia: Sigmodontinae) in several populations in Brazil and examined the meiotic behaviour of this chromosome in heterozygotes. We observed an orderly pairing of all chromosomes at pachytene in heterozygotes for the inverted chromosome 3. No indication of meiotic arrest and germ-cell death was found. Electron microscopy of synaptonemal complexes and conventional meiotic analysis indicated strictly nonhomologous synapsis and crossing-over suppression in the inverted region in the heterozygotes, which prevent the formation of unbalanced gametes. Thus, the pericentric inversion in chromosome 3 does not apparently result in any selective disadvantages in heterozygous carriers. In the majority of the populations studied, the frequencies of acrocentric homozygotes, metacentric homozygotes, and heterozygotes were in Hardy-Weinberg equilibrium. However, in some populations, we detected an excess of heterozygotes and a deficiency of acrocentric homozygotes.     

Phylogeography of sex ratio and multiple mating in stalk-eyed flies from southeast Asia

The factors maintaining sex chromosome meiotic drive, or sex ratio (SR), in natural populations remain uncertain. Coevolution between segregation distortion and modifiers should produce transient SR distortion while selection can result in a stable polymorphism. We hypothesize that if SR is maintained by selection, then phylogenetically related populations should exhibit similar SR frequency and intensity. Furthermore, when drive is present, females should mate with multiple males more often both to insure fertility and to increase the probability of producing male progeny. In this paper we report on variation in SR frequency and multiple mating among seven populations and three species of stalk-eyed flies, genus Cyrtodiopsis, from southeast Asia. Using a phylogenetic hypothesis based on 1100 bp of mtDNA sequence we find that while sex chromosome meiotic drive is present in all populations of C. whitei and C. dalmanni, the frequency and intensity of drive only differs between populations or species with greater than 4.8% sequence divergence. The frequency of females mating with multiple males is higher in populations with SR. In addition, SR males mate less often, possibly to compensate for sperm depletion. Our results suggest that sex chromosome drive is maintained by balancing selection in populations of C. whitei and C. dalmanni. Nevertheless, coevolution between drive and suppressors deserves further study.     

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.     

EVOLUTION OF DRIVING X CHROMOSOMES AND RESISTANCE FACTORS IN EXPERIMENTAL POPULATIONS OF DROSOPHILA SIMULANS

Sex-ratio drive is a particular case of meiotic drive, described in several Drosophila species, that causes males bearing driving X chromosome to produce a large excess of females in their progeny. In Drosophila simulans, driving X chromosomes and resistance factors located on the Y chromosome and on the autosomes have been previously reported. In this paper, we report the study of the dynamics of sex-ratio factors in experimental populations. We followed the evolution in frequency of driving X chromosomes in the absence of resistance factors and the evolution of resistance factors in the presence of driving X chromosomes. The driving X chromosome was lost, contrarily to theoretical expectations that predict its rapid invasion. Autosomal resistances increased in frequency, and resistant Y chromosomes invaded the population very quickly, as predicted by theoretical models. Fitness measurements showed that the loss of the driving X chromosome was due to a strong deleterious effect that was expressed only when distorting males were in competition with standard males. However, the spread of autosomal resistances reduced this deleterious effect. Implications for the maintenance of polymorphism in natural populations are discussed.     

SUPPRESSION OF SEX-RATIO MEIOTIC DRIVE AND THE MAINTENANCE OF Y-CHROMOSOME POLYMORPHISM IN DROSOPHILA

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.     

THE CONTRIBUTION OF FEMALE MEIOTIC DRIVE TO THE EVOLUTION OF NEO‐SEX CHROMOSOMES

Sex chromosomes undergo rapid turnover in certain taxonomic groups. One of the mechanisms of sex chromosome turnover involves fusions between sex chromosomes and autosomes. Sexual antagonism, heterozygote advantage, and genetic drift have been proposed as the drivers for the fixation of this evolutionary event. However, all empirical patterns of the prevalence of multiple sex chromosome systems across different taxa cannot be simply explained by these three mechanisms. In this study, we propose that female meiotic drive may contribute to the evolution of neo‐sex chromosomes. The results of this study showed that in mammals, the XY₁Y₂ sex chromosome system is more prevalent in species with karyotypes of more biarmed chromosomes, whereas the X₁X₂Y sex chromosome system is more prevalent in species with predominantly acrocentric chromosomes. In species where biarmed chromosomes are favored by female meiotic drive, X‐autosome fusions (XY₁Y₂ sex chromosome system) will be also favored by female meiotic drive. In contrast, in species with more acrocentric chromosomes, Y‐autosome fusions (X₁X₂Y sex chromosome system) will be favored just because of the biased mutation rate toward chromosomal fusions. Further consideration should be given to female meiotic drive as a mechanism in the fixation of neo‐sex chromosomes.     

Experimental and Theoretical Analysis of the "Sex-Ratio" Polymorphism in DROSOPHILA PSEUDOOBSCURA

The Sex-ratio chromosome (SR) is a widespread, multiply inverted rearrangement of the X chromosome present in several species of Drosophila. Male carriers transmit mostly X-bearing sperm. In the absence of strong counteracting selection, SR is expected to increase rapidly to fixation, causing extinction. The present study incorporates a selection-components analysis of SR in laboratory populations, using the closely linked Esterase-5 locus as a marker. Estimated fitnesses show directional viability selection against SR in both males and females, heterosis for fertility and no significant effects on virility, the male adult component of fitness. Estimated fitnesses satisfy conditions for protected polymorphism and accurately predict gene-frequency trajectories in experimental populations. A model of SR gene-frequency evolution is developed, which incorporates sex-linkage, meiotic drive, viability, fertility and virility selecton. We show that conditions for protected polymorphisms are not unduly restrictive and that differential fitness among males is not sufficient for protected polymorphism, irrespective of the degree of meiotic drive.     

Population Genetic Structure of the Grasshopper Eyprepocnemis plorans in the South and East of the Iberian Peninsula

The grasshopper Eyprepocnemis plorans subsp. plorans harbors a very widespread polymorphism for supernumerary (B) chromosomes which appear to have arisen recently. These chromosomes behave as genomic parasites because they are harmful for the individuals carrying them and show meiotic drive in the initial stages of population invasion. The rapid increase in B chromosome frequency at intrapopulation level is thus granted by meiotic drive, but its spread among populations most likely depends on interpopulation gene flow. We analyze here the population genetic structure in 10 natural populations from two regions (in the south and east) of the Iberian Peninsula. The southern populations were coastal whereas the eastern ones were inland populations located at 260–655 m altitude. The analysis of 97 ISSR markers revealed significant genetic differentiation among populations (average G_ST =  0.129), and the Structure software and AMOVA indicated a significant genetic differentiation between southern and eastern populations. There was also significant isolation by distance (IBD) between populations. Remarkably, these results were roughly similar to those found when only the markers showing low or no dropout were included, suggesting that allelic dropout had negligible effects on population genetic analysis. We conclude that high gene flow helped this parasitic B chromosome to spread through most of the geographical range of the subspecies E. plorans plorans.     

Molecular analysis of nondisjunction in mice heterozygous for a Robertsonian translocation

A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: 1. The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%. 2. Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters. 3. There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction. 4. Strain background did not play an appreciable role in nondisjunction frequency. 5. The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males. 6. The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals.     

Factors responsible for a karyotypic polymorphism in the common shrew, Sorex araneus

A Robertsonian karyotypic polymorphism in the common shrew in the Oxford area, first described in the 1950s, was re-examined. The polymorphism involves chromosome arm combinations kq, no and pr (characteristic of the Oxford karyotypic race), ko (characteristic of the Hermitage karyotypic race) and jl (found in both races). The polymorphism for jl was sporadic along a north-south transect through the Oxford area, with the frequency of the twin-acrocentric morph never exceeding 10%. The frequency of the Oxford race-specific metacentrics decreased and the frequency of the Hermitage race-specific metacentric ko increased from north to south along the transect. At a latitudinal grid reference of about 180 km, there was a high frequency of individuals with chromosome arms k, n, o and q in the ancestral acrocentric state. This was coincident with the area of occurrence of ko-kq and ko-no Oxford-Hermitage hybrids. Such hybrids are double Robertsonian heterozygotes with monobrachial homology and are likely to suffer reduced fertility in consequence. It is proposed that this is a source of selection against the monobrachial hybrids and hence results in an increase in frequency of the acrocentric morphs. This scheme goes some way to explain the clines of polymorphism for arm combinations kq, no and ko, but it is suggested that other selective factors are involved. It cannot explain the cline of polymorphism for pr, which is in general terms similar to that for kq and no, but is more shallow and centred further north.     

Sex Chromosome Meiotic Drive in Stalk-Eyed Flies

Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (X(d)). Relatively high frequencies of X(d) in C. dalmanni and C. whitei (13-17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of X(d). Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with X(d), modifying Y chromosomes (Y(m)) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex-linked polymorphisms and consider the impact of X(d) on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.     

Meiotic drive of t-haplotypes: segregation of chromosomes in mice with partial trisomy

The properties of the t haplotypes, specific mutant states of the proximal region of chromosome 17 in the house mouse keep renewing interest. One such property is increased transmission of the t haplotype from heterozygous t/+ males to their offspring. By means of reciprocal translocation T (16; 17)43H, we have constructed males with tertiary trisomy 17 (+T43/++/RB7+) carrying Robertsonian translocation Rb(16.17)7Bnr. The offspring of these males was viable when sperm of +T43/++ and Rb7+ was used. The segregation patterns in the offspring of t-bearing trisomics were analysed on days 16-18 of embryonic development. It was found that in the case when the t haplotype is on the normal acrocentric (male male ++T43/+t12+/Rb7++), its presence in the gamete +t12+/++T43 does not produce meiotic drive. However, when t6 is on Rb7, meiotic drive was equal to 80%. It is concluded that the presence of a normal homolog and a t-bearing chromosome in sperm does not result in meiotic drive. Possible mechanisms of meiotic drive of the t haplotypes are discussed.     

Impact of Robertsonian translocation on meiosis and reproduction: an impala (Aepyceros melampus) model

The captive bred animal populations showing centric fusion polymorphism can serve as a model for analysis of the impact of the rearrangement on meiosis and reproduction. The synapsis of homologous chromosomes and the frequency and distribution of meiotic recombination events were studied in pachytene spermatocytes of captive bred male impalas (Aepyceros melampus) polymorphic for der(14;20) by immunofluorescent analysis and fluorescence in situ hybridization. The chromosomes 14 and 20 involved in the centric fusion were significantly shorter due to the loss of sat I repeats indicating ancient origin of the rearrangement. The fused chromosome and the normal acrocentric chromosomes 14 and 20 formed trivalent in pachynema which showed either protruding proximal ends of the acrocentric chromosomes or single axis with synaptic adjustment in the pericentromeric region. There was no significant difference in the number of recombination events per cell between the group of translocation heterozygotes and the animals with normal karyotype. A significant reduction in the number of recombination events was observed in the trivalent chromosomes compared to the normal chromosomes 14 and 20. The level of the recombination reduction was related to the trivalent configuration. The centric fusion der(14;20) was not apparently demonstrated by any spermatogenic defects or reproductive impairment in heterozygous impalas. However, the high incidence of the chromosomal polymorphism within the captive bred population shows the importance of cytogenetic examinations in captive breeding and wildlife conservation programs, especially in the case of reintroduction of the endangered species.     

Sperm competition and the dynamics of X chromosome drive: stability and extinction

Several empirical studies of sperm competition in populations polymorphic for a driving X chromosome have revealed that Sex-ratio males (those carrying a driving X) are at a disadvantage relative to Standard males. Because the frequency of the driving X chromosome determines the population-level sex ratio and thus alters male and female mating rates, the evolutionary consequences of sperm competition for sex chromosome meiotic drive are subtle. As the SR allele increases in frequency, the ratio of females to males also increases, causing an increase in the male mating rate and a decrease in the female mating rate. While the former change may exacerbate the disadvantage of Sex-ratio males during sperm competition, the latter change decreases the incidence of sperm competition within the population. We analyze a model of the effects of sperm competition on a driving X chromosome and show that these opposing trends in male and female mating rates can result in two coexisting locally stable equilibria, one corresponding to a balanced polymorphism of the SR and ST alleles and the second to fixation of the ST allele. Stochastic fluctuations of either the population sex ratio or the SR frequency can then drive the population away from the balanced polymorphism and into the basin of attraction for the second equilibrium, resulting in fixation of the SR allele and extinction of the population.     

TO WHAT EXTENT DO DIFFERENT TYPES OF SEX RATIO DISTORTERS INTERFERE?

Within the Diptera, two different selfish genetic elements are known to cause the production of female-biased sex ratios: maternally inherited bacteria that kill male zygotes (male-killers), and X chromosomes causing the degeneration of Y-bearing sperm in males (meiotic drive). We here develop a mathematical model for the dynamics of these two sex-ratio distorters where they co-occur. We show that X chromosome meiotic drive elements can be expected to substantially lower the equilibrium frequency of male-killers and can even lead to their extinction. Conversely, male-killers can also decrease the equilibrium frequency of X drivers and cause their extinction. Thus, we predict that there will be some complementarity in the incidence of X chromosome meiotic drive and male-killing in natural populations, with a lower than expected number of species bearing both elements.     

Meiotic drive of t haplotypes: chromosome segregation in mice with tertiary trisomy

The properties of the t haplotypes, specific mutant states of the proximal region of chromosomes 17 in the house mouse, are of continuing interest. One such property is increased transmission of the t haplotype by heterozygous t/+ males to offspring. Using the reciprocal translocation T(16;17)43H we have constructed males with tertiary trisomy of chromosome 17 (+T43/+ +/Rb7+) carrying the Robertsonian translocation Rb(16.17)7Bnr. Only the progeny of these males which had inherited either T43/+ or Rb7 from their male parent were viable. The segregation patterns in the offspring of t-bearing trisomics were analysed on days 16-18 of embryonic development. It was found that, when the t12 haplotype is in the normal acrocentric (males+ +T43/+ t12 + /Rb7+ +), its presence in the gamete +t12+/+ + T43 does not produce meiotic drive. However, when t6 is in Rb7, meiotic drive was observed: 80% of offspring carried the t haplotype. It is concluded that the meiotic drive is probably inhibited by the presence of a normal homologue of chromosome 17 in the same sperm. Possible mechanisms for the t haplotype effect are discussed.     

Integration of a B chromosome into the A genome of a wasp,revisited

A previous study showed that in the haplodiploid solitary wasp Trypoxylon albitarse, most individuals carry one B chromosome per haploid genome, the same dosage as the standard (A) chromosomes, indicating a possible regularization of B-chromosome meiotic behaviour and its integration into the A genome. In a new sampling, we have analysed 15 populations (including 9 out of the 10 previously analysed) to test the evolution of this integration process. The new results provide a direct report of the invasion process in the Porto Firme population, where B frequency has dramatically increased in only four generations. In the populations from the Viçosa region, however, B frequency has remained stable, although the principal B type, the metacentric one, has increased in frequency at the expense of the acrocentric one in several populations. The implications of these new results on the hypothesis of the integration of these B chromosomes, as regular members of the A genome, are discussed.     

Natural Selection and Y-Linked Polymorphism

Several population genetic models allowing natural selection to act on Y-linked polymorphism are examined. The first incorporates pleiotropic effects of a Y-linked locus, such that viability, segregation distortion, fecundity and sexual selection can all be determined by one locus. It is shown that no set of selection parameters can maintain a stable Y-linked polymorphism. Interaction with the X chromosome is allowed in the next model, with viabilities determined by both X- and Y-linked factors. This model allows four fixation equilibria, two equilibria with X polymorphism and a unique point with both X- and Y-linked polymorphism. Stability analysis shows that the complete polymorphism is never stable. When X- and Y-linked loci influence meiotic drive, it is possible to have all fixation equilibria simultaneously unstable, and yet there is no stable interior equilibrium. Only when viability and meiotic drive are jointly affected by both X- and Y-linked genes can a Y-linked polymorphism be maintained. Unusual dynamics, including stable limit cycles, are generated by this model. Numerical simulations show that only a very small portion of the parameter space admits Y polymorphism, a result that is relevant to the interpretation of levels of Y-DNA sequence variation in natural populations.