Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

Abstract

The infertility of hybrids between closely related species is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid sterility gene causes failure of meiotic chromosome synapsis and infertility in male hybrids between mouse strains derived from two mouse subspecies. Within species Prdm9 determines the sites of programmed DNA double-strand breaks and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids and analyzed their ability to form synaptonemal complexes and rescue male fertility. Twenty-seven or more Mb of consubspecific homology fully restored synapsis in a given autosomal pair and we predicted that two symmetric DSBs or more per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionary diverged homologous chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.