LAUSR

Hybrid sterility contributes to speciation by preventing gene flow between related taxa. Prdm9, the first and only hybrid male sterility (HMS) gene known in vertebrates, predetermines the sites of recombination between homologous chromosomes and their synapsis in early meiotic prophase. The asymmetric binding of PRDM9 to heterosubspecific homologs of Mus m. musculus x Mus m. domesticus F1 hybrids and increase of PRDM9-independent DNA double-strand break (DSB) hotspots results in difficult to repair DSBs, incomplete synapsis of homologous chromosomes and meiotic arrest at the first meiotic prophase. Here we show that Prdm9 behaves as a major HMS gene in mice outside the Mus m. musculus x Mus m. domesticus F1 hybrids, in the genomes composed of Mus m. castaneus and Mus m. musculus chromosomes segregating on the Mus m. domesticus background. The Prdm9cst/dom2 (castaneus/domesticus) allelic combination secures meiotic synapsis, testes weight and sperm count within physiological limits, while the Prdm9msc1/dom2 (musculus/domesticus) males show a range of fertility impairment. Out of five quantitative trait loci contributing to the Prdm9msc1/dom2-related infertility, four control either meiotic synapsis or fertility phenotypes and one controls both, synapsis and fertility. Whole-genome genotyping of individual chromosomes showed preferential involvement of nonrecombinant musculus chromosomes in asynapsis in accordance with the chromosomal character of HMS. Moreover, we show that the overall asynapsis rate can be estimated solely from the genotype of individual males by scoring the effect of nonrecombinant musculus chromosomes. Prdm9-controlled HMS represents an example of genetic architecture of HMS consisting of genic and chromosomal components.