Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.

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Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

Genetics ◽

10.1093/genetics/iyab136 ◽

2021 ◽

Author(s):

Brett A Haines ◽

Francesca Barradale ◽

Beth L Dumont

Keyword(s):

Sex Ratio ◽

Sex Chromosome ◽

Preliminary Evidence ◽

Collaborative Cross ◽

Mouse Population ◽

Mendelian Expectation ◽

Genetic Mechanisms ◽

Ratio Distortion ◽

Different Strains ◽

Sex Ratio Distortion

Abstract In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.

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Sex Ratios in a Warming World: Thermal Effects on Sex-Biased Survival, Sex Determination, and Sex Reversal

Journal of Heredity ◽

10.1093/jhered/esab006 ◽

2021 ◽

Vol 112 (2) ◽

pp. 155-164

Author(s):

Suzanne Edmands

Keyword(s):

High Temperature ◽

Sex Ratio ◽

Sex Determination ◽

Heat Tolerance ◽

Sex Ratios ◽

Sex Reversal ◽

Survival Sex ◽

Ratio Distortion ◽

Warming World ◽

Sex Ratio Distortion

Abstract Rising global temperatures threaten to disrupt population sex ratios, which can in turn cause mate shortages, reduce population growth and adaptive potential, and increase extinction risk, particularly when ratios are male biased. Sex ratio distortion can then have cascading effects across other species and even ecosystems. Our understanding of the problem is limited by how often studies measure temperature effects in both sexes. To address this, the current review surveyed 194 published studies of heat tolerance, finding that the majority did not even mention the sex of the individuals used, with <10% reporting results for males and females separately. Although the data are incomplete, this review assessed phylogenetic patterns of thermally induced sex ratio bias for 3 different mechanisms: sex-biased heat tolerance, temperature-dependent sex determination (TSD), and temperature-induced sex reversal. For sex-biased heat tolerance, documented examples span a large taxonomic range including arthropods, chordates, protists, and plants. Here, superior heat tolerance is more common in females than males, but the direction of tolerance appears to be phylogenetically fluid, perhaps due to the large number of contributing factors. For TSD, well-documented examples are limited to reptiles, where high temperature usually favors females, and fishes, where high temperature consistently favors males. For temperature-induced sex reversal, unambiguous cases are again limited to vertebrates, and high temperature usually favors males in fishes and amphibians, with mixed effects in reptiles. There is urgent need for further work on the full taxonomic extent of temperature-induced sex ratio distortion, including joint effects of the multiple contributing mechanisms.

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Sex Chromosome Meiotic Drive in Stalk-Eyed Flies

Genetics ◽

10.1093/genetics/147.3.1169 ◽

1997 ◽

Vol 147 (3) ◽

pp. 1169-1180 ◽

Cited By ~ 6

Author(s):

Daven C Presgraves ◽

Emily Severance ◽

Gerald S Willrinson

Keyword(s):

Sex Ratio ◽

Sex Chromosome ◽

Sex Ratios ◽

Natural Populations ◽

Meiotic Drive ◽

Operational Sex Ratio ◽

Genetic Modifiers ◽

Ratio Distortion ◽

The Impact ◽

Sex Ratio Distortion

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 (Xd). Relatively high frequencies of Xd 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 Xd. 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 Xd, modifying Y chromosomes (Ym) 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 Xd on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.

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Horizontal transfer of parasitic sex ratio distorters between crustacean hosts

Parasitology ◽

10.1017/s0031182098002820 ◽

1998 ◽

Vol 117 (1) ◽

pp. 15-19 ◽

Cited By ~ 13

Author(s):

A. M. DUNN ◽

T. RIGAUD

Keyword(s):

Sex Ratio ◽

Sex Determination ◽

Host Specificity ◽

Host Species ◽

Horizontal Transfer ◽

Parasite Infection ◽

Parasite Transmission ◽

Ratio Distortion ◽

Sex Ratio Distortion ◽

Crustacean Host

Parasitic sex ratio distorters were artificially transferred within and between crustacean host species in order to study the effects of parasitism on host fitness and sex determination and to investigate parasite–host specificity. Implantation of Nosema sp. to uninfected strains of its Gammarus duebeni host resulted in an active parasite infection in the gonad of recipient females and subsequent transovarial parasite transmission. The young of artificially infected females were feminized by the parasite, demonstrating that Nosema sp. is a cause of sex ratio distortion in its host. In contrast, we were unable to cross-infect Armadillidium vulgare with the feminizing microsporidian from G. duebeni or to cross-infect G. duebeni with the feminizing bacterium Wolbachia sp. from A. vulgare.

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Environmental Influences on Crustacean Sex Determination and Reproduction: Environmental Sex Determination, Parasitism, and Pollution

Reproductive Biology ◽

10.1093/oso/9780190688554.003.0014 ◽

2020 ◽

pp. 394-428

Author(s):

Alison M. Dunn ◽

Thierry Rigaud ◽

Alex T. Ford

Keyword(s):

Environmental Factors ◽

Sex Ratio ◽

Sex Determination ◽

Environmental Influences ◽

Host Population ◽

Adaptive Mechanism ◽

Environmental Sex Determination ◽

Individual Fitness ◽

Ratio Distortion ◽

Sex Ratio Distortion

This chapter reviews the influences of environmental factors on sex determination, sex ratios, and reproductive behavior in the Crustacea, focusing in particular on amphipod and isopod examples. A range of abiotic and biotic environmental factors influence reproduction in Crustacea, including temperature, day length, pollutants, and parasites. Individual crustaceans may benefit from these environmental influences, but in other cases, reproductive biology responses to biotic and abiotic environments may be detrimental to individual fitness. Environmental Sex Determination (ESD) falls into the former category. ESD is an adaptive mechanism of sex determination that is rare, but has evolved in diverse taxa. Evidence from gammarid amphipods is used to explore the evolution of ESD in response to a patchy environment. While ESD is an adaptive mechanism of sex determination, the impact of other environmental factors can be very costly. Parasitic castrators can lead to a reduction or total cessation of reproduction in crustacean hosts, driving population declines. In contrast, parasitic feminizers convert male hosts into females, enhancing maternal parasite transmission but also leading to sex ratio distortion in the host population. The chapter discusses parasite-host coevolutionary conflict and reviews evidence that selection on the host in response to parasitic sex ratio distortion has led to altered mate choice in amphipods, and to the evolution of a novel system of sex determination in isopods. Human-induced environmental influences can also be seen in Crustacea, and the chapter discusses how parasites, ESD, and endocrine-disrupting chemicals can each affect sex determination and lead to abnormal intersex phenotypes. It ends by highlighting areas for future research on the diverse world of crustacean reproduction.

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Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution

10.1101/649707 ◽

2019 ◽

Cited By ~ 1

Author(s):

CC Rathje ◽

EEP Johnson ◽

D Drage ◽

C Patinioti ◽

G Silvestri ◽

...

Keyword(s):

Sex Ratio ◽

Chromosome Evolution ◽

Sex Chromosome ◽

Mammalian Sperm ◽

Evolutionary Force ◽

Sperm Development ◽

Cast Doubt ◽

Ratio Distortion ◽

Haploid Selection ◽

Sex Ratio Distortion

SummaryThe search for morphological or physiological differences between X- and Y-bearing mammalian sperm has provoked controversy for decades. Many potential differences have been proposed, but none validated, while accumulating understanding of syncytial sperm development has cast doubt on whether such differences are possible even in principle. We present the first ever mammalian experimental model to trace a direct link from a measurable physiological difference between X- and Y-bearing sperm to the resulting skewed sex ratio. We show that in mice with deletions on chromosome Yq, birth sex ratio distortion is due to a relatively greater motility of X-bearing sperm, and not to any aspect of sperm/egg interaction. Moreover, the morphological distortion caused by Yq deletion is more severe in Y-bearing sperm, providing a potential hydrodynamic basis for the altered motility. This reinforces a growing body of work indicating that sperm haploid selection is an important and underappreciated evolutionary force.

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EXPERIMENTAL POPULATION GENETICS OF MEIOTIC DRIVE SYSTEMS. III. NEUTRALIZATION OF SEX-RATIO DISTORTION IN DROSOPHILA THROUGH SEX-CHROMOSOME ANEUPLOIDY

Genetics ◽

10.1093/genetics/98.2.317 ◽

1981 ◽

Vol 98 (2) ◽

pp. 317-334

Author(s):

Terrence W Lyttle

Keyword(s):

Sex Ratio ◽

Y Chromosome ◽

Sex Chromosome ◽

Meiotic Drive ◽

Generation Model ◽

Sex Chromosome Aneuploidy ◽

Population Extinction ◽

Chromosome Aneuploidy ◽

Ratio Distortion ◽

Sex Ratio Distortion

ABSTRACT Laboratory populations of Drosophila melanogaster were challenged by pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes extreme sex-ratio distrotion and can ultimately lead to population extinction. Populations normally respond by the gradual accumulation of drive suppressors, and this reduction in strength of distortion allows the sex ratio to move closer to the optimal value of 1:1. One population monitored, however, was rapidly able to neutralize the effects of sex-ratio distortion by the accumulation of sex-chromosome aneuploids (XXY, XYY). This apparently occurs because XX-bearing eggs, produced in relatively high numbers (~4%) by XXY genotypes, become the main population source of females under strong Y-chromosome drive. Computer simulation for a discrete generation model incorporating random mating with differences in fitness and segregation permits several predictions that can be compared to the data. First, sex-chromosome aneuploids should rapidly attain equilibrium, while stabilizing the population at ~60% males. This sex ratio should be roughly independent of the strength of the meiotic drive. Moreover, conditions favoring the accumulation of drive suppressors (e.g., weak distortion, slow population extinction) are insufficient for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong distortion, low production of females) lead to population extinction before drive suppressors can accumulate. Thus, the different mechanisms for neutralizing sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome aneuploidy are potentially co-adaptive, since under some conditions neither will survive alone. Finally, these results suggest the possibility that genetic variants promoting sex-chromosome nondisjunction may have a selective advantage in natural populations faced with sex-ratio distortion.

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