PgmNr P350: An X×Y genetic interaction mediates global crossover frequency in house mice.

Authors:
Beth Dumont


Institutes
North Carolina State University, Raleigh, NC.


Abstract:

The rate of recombination is a complex trait, with quantitative variation between individuals shaped by multiple genetic factors. Previously, I identified a large-effect X-linked QTL underlying recombination rate differences between males of two house mouse subspecies, Mus musculus musculus (Mmm) and M. m. castaneus (Mmc). Surprisingly, at this locus, the allele conferring the increase in recombination rate derives from the low recombination rate Mmc parent. This observation suggests that the native Mmc genome harbors at least one recombination rate suppressor that overrides the effect of this recombination-increasing allele. Here, I present multiple lines of experimental evidence to demonstrate that one of these suppressors is on the Y chromosome. Using data from the Collaborative Cross panel of recombinant house mice, I estimate that this Y-linked recombination rate modifier decreases global crossover frequency by ~1 crossover per meiosis. I further show that animals with XMmc/YMmm and XMmm/YMmc genotypes have reduced recombination frequencies, suggesting an antagonistic genetic interaction driven by intersubspecific combinations of alleles on the sex chromosomes. I nominate a pair of homologous, ampliconic, and interacting genes on the X and Y as compelling candidates underpinning these intriguing patterns. Together, these findings suggest that recombination rates may be shaped, in part, by intragenomic conflict and offer new genetic explanations for the striking sex differences in the crossover landscape.