Recombination Rates Are Governed by Sex-Specific Evolutionary Programs in House Mice

Recombination rates vary markedly across species, populations, and sexes. In house mice ( Mus musculus ), this variation is particularly pronounced. Prior studies have established large differences in global recombination rates between M. musculus subspecies and inbred strains, with males exhibiting more extensive variation than females. The observation of sex-limited variation has prompted the hypothesis that male and female recombination rates may evolve by distinct evolutionary mechanisms in M. musculus . Here, we set out to formally evaluate this hypothesis in a phylogenetic framework using a dataset of cytogenetic sex-specific genome-scale crossover rate estimates from >6000 single meiotic cells from 31 genetically diverse inbred mouse strains spanning five Mus species and four M. musculus subspecies. Using phylogenetic comparative methods, we document a significant phylogenetic signal in male recombination rates, but female recombination rates show no clear phylogenetic trend. Males from M. m. musculus exhibit a large increase in recombination rate compared to other M. musculus subspecies, prompting us to explicitly test models of lineage-specific trait evolution. We show that the phylogenetic distribution of male recombination rates is best explained by an evolutionary model that allows a unique adaptive optimum along the M. m. musculus lineage, whereas female recombination rates are well-explained by a simplified model with a single global trait optimum. Taken together, our findings confirm the hypothesis that recombination rate evolution in house mice is governed by distinct sex-specific evolutionary regimes and motivate future efforts to ascertain the sex-specific selective pressures and sex-specific genetic architectures that underlie these observations.