The evolutionary dynamics of meiotic recombination initiation in mice

Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. The DNA double strand breaks (DSBs) that initiate meiotic recombination are directed by sequence-specific DNA binding of the PRDM9 protein. Gradual elimination of PRDM9 binding sites by gene conversion is thought to result in the hotspot erosion while mutations affecting DNA binding specificity of PRDM9 will create the new sets of hotspots. To better understand evolutionary turnover of recombination hotspots we mapped DSB hotspots in six inbred mouse strains representing all four major subspecies of Mus musculus and in their F1 hybrids. We found that hotspot erosion governs the preferential usage of some Prdm9 alleles over others in hybrid mice and increases sequence diversity specifically at hotspots that become active in the hybrids. As crossovers are disfavored at such hotspots, we propose that sequence divergence generated by hotspot turnover creates impediments for recombination in hybrids, potentially leading to reduction in fertility and eventually, speciation. Overall design: Detection of meiotic DNA double strand breaks in testis of 26 mouse strains and F1 hybrids. Update: [05-30-2023] Sample GSM1954846 was removed because it was incorrectly labeled as CASTfx13Rm (CAST female crossed with a 13R strain male).