Natural variation in the zinc-finger-encoding exon ofPrdm9affects hybrid sterility phenotypes in mice

Abstract

AbstractPRDM9-mediated reproductive isolation was first described in the progeny ofMus musculus musculus(MUS) PWD/Ph andMus musculus domesticus(DOM) C57BL/6J inbred strains. These male F1-hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between thePrdm9gene and hybrid sterility locusHstx2. We identified fourteen alleles ofPrdm9in Exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, eight of which are novel. The samePrdm9allele was found in all mice bearing introgressedt-haplotypes, encompassingPrdm9and inversions preventing recombination with wildtype Chr 17. We asked whether seven novelPrdm9alleles in MUS populations and thet-haplotype allele in one MUS and three DOM populations inducePrdm9-mediated reproductive isolation. The results show that only combinations of thedom2allele of DOM origin and the MUSmsc1allele ensure complete infertility of intersubspecific hybrids outside the context of inbred mouse strains. The results further indicate that the erasure of PRDM9msc1binding motifs may be shared by MUS mice from populations with differentPrdm9alleles, implicating that erased PRDM9 binding motifs may be uncoupled from their corresponding PRDM9 zinc finger arrays at the population level. Our data corroborate the model ofPrdm9-mediatedhybrid sterility beyond inbred strains of mice and suggest that sterility alleles ofPrdm9may be rare.