Dissecting the genetic architecture of F1 hybrid sterility in house mice

Hybrid sterility as a postzygotic reproductive isolation mechanism has been studied for over 80 years, yet the first identifications of hybrid sterility genes in Drosophila and mouse are quite recent. To study the genetic architecture of F_1 hybrid sterility between young subspecies of house mouse Mus m. domesticus and Mus m. musculus we conducted QTL analysis of a backcross between inbred strains representing these two subspecies and probed the role of individual chromosomes in hybrid sterility using the inter-subspecific chromosome substitution strains. We provide direct evidence that the asymmetry in male infertility between reciprocal crosses is conferred by the middle region of Mus m. musculus Chr X, thus excluding other potential candidates such as Y, imprinted genes, and mitochondrial DNA. QTL analysis identified strong hybrid sterility loci on Chr 17 and Chr X and predicted a set of interchangeable autosomal loci, a subset of which is sufficient to activate the Dobzhansky-Muller...