A simplified scheme of a pair of homologous chromosomes in PWD (Mus m. musculus) and B6 (Mus m. domesticus) mice and sterile (PWD x B6) intersubspecific male F1 hybrids. Eroded PRDM9B6 binding sites are not recognized or hardly recognized by the PRDM9B6 zinc-finger array in B6 meiosis, but the same sites were saved from erosion during the evolution of the other subspecies. Thus, in (PWD x B6)F1 hybrids PRDM9B6 often binds to the sites on PWD chromosome that are erased on B6 homolog and, vice versa, PRDM9PWD more often binds to the sites on B6 homolog, eroded in PWD. The proportion of such asymmetric sites exceeds 70% of all DSBs in (PWD x B6)F1 hybrid meiosis (Davies et al., 2016) and interferes with chromosome synapsis and meiotic progression. The higher activity of these asymmetric hotspots estimated by DMC1-ChIP-seq is explained by a delay or failure of DSB repair.