Extensive sex differences at the initiation of genetic recombination

Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at recombination initiation by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to 15-fold differences in hotspot usage between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex-biased hotspots appear to be partly determined by chromosome structure, and DNA methylation, absent in females at the onset of meiosis, plays a substantial role. Sex differences are also evident later in meiosis as the repair frequency of distal meiotic breaks as crossovers diverges in males and females. Suppression of distal crossovers may help to minimize age-related aneuploidy that arises due to cohesion loss during dictyate arrest in females.