Extensive sex differences at the initiation of genetic recombination

Abstract

Homologous recombination in meiosis is initiated by programmed DNA double strand breaks (DSBs) and DSB repair as a crossover is essential to prevent chromosomal abnormalities in gametes. Sex differences in recombination have been previously observed by analyses of recombination end-products. To understand when and how sex differences are established, we built genome-wide maps of meiotic DSBs in both male and female mice. We found that most recombination initiates at sex-biased DSB hotspots. Local context, the choice of DSB targeting pathway and sex-specific patterns of DNA methylation give rise to these differences. Sex differences are not limited to the initiation stage, as the rate at which DSBs are repaired as crossovers appears to differ between the sexes in distal regions. This uneven repair patterning may be linked to the higher aneuploidy rate in females. Together, these data demonstrate that sex differences occur early in meiotic recombination.