Natural variation inPrdm9affecting hybrid sterility phenotypes

Abstract

PRDM9-mediated reproductive isolation was first described in offspring ofMus musculus musculusstrain PWD/Ph andMus musculus domesticusstrain C57BL/6J. Male F1-hybrids do not complete chromosome synapsis and arrest meiosis at Prophase I. Currently, all data supports an oligogenic control of hybrid sterility based on incompatibilities between PRDM9 and hybrid-sterility locusHstx2inMus musculushybrids. Erosion of PRDM9 binding sites was proposed to result in asymmetric binding on diverged homologs of intersubspecific F1hybrids. Numerous alleles ofPrdm9have been characterized for different subspecies ofMus musculus, but only a few were analyzed for their impact on hybrid sterility. We analyzedPrdm9diversity in natural wild mouse populations from Europe, Asia, and the Middle East and identified several novelPrdm9alleles. We established that a singlePrdm9allele is associated witht-haplotype Chromosome 17 in all three subspecies ofMus musculusand characterized the phylogenetic relationships of novelPrdm9alleles with established sterility alleles. Novel wildPrdm9alleles produced F1-hybrid male offspring that were either fertile or showedPrdm9-dependent reduction of fertility and high levels of asynapsis. Fertility or sterility phenotypes segregated purely with thePrdm9genotype, although theMus musculus musculusbackground varied. Our data substantiate that hybrid sterility is under oligogenic control withPrdm9as the leading player but is consistent with a nonbinary regulation of hybrid sterility and gradual fertility decline when homologs diverge.