X-Chromosome Control of Genome-Scale Recombination Rates in House Mice

Abstract

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus, were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females.

A first genetic portrait of synaptonemal complex variation

“…If different optima for recombination rates exist between males and females, the X chromosome may accumulate rate modifiers in an evolutionary arms race. Male and female mice also show contrasting patterns of divergence in recombination rate, consistent with such a hypothesis [25,97].…”

High male specific contribution of the X-chromosome to individual global recombination rate in dairy cattle

“…Variable contribution is also observed in other species. Dumont [ 26 ] reported that associations of X-linked variants with GRR remained rare in many species, including human, but also that large effect X-linked loci had been identified in mice [ 19 , 25 ].…”

“…Several examples of X-linked genes causing infertility or hybrid sterility, and also controlling meiosis, have been reported (e.g., [ 24 , 25 ]). Further, X-linked loci could also explain the observed differences in GRR between sexes as suggested by Dumont and Payseur [ 19 ] and Dumont [ 26 ]. For these different reasons, the X-chromosome might make an important contribution to genetic variance of GRR.…”