The genetic basis of speciation in house mice

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Identifying the genes responsible for these reproductive barriers provides insights in to the process of speciation. Although tremendous progress has been made identifying quantitative trait loci (QTL) and genes responsible for reproductive isolation, genome-wide characterization of these barriers has been limited to a small number of taxa. Furthermore, little is known how these incompatibilities accumulate in young species groups. This approach requires comparative genetic mapping of reproductive barriers across multiple species pairs in combination with fine-scale estimates of phylogenetic histories across the genome.;With recently diverged subspecies, house mice are a powerful system to study the genetic basis of reproductive isolation across several subspecies. In this dissertation, I conducted F2 intercrosses between two subspecies pairs of house mice (M. m. musculus-M. m. domesticus and M. m. castaneus-M. m. domesticus) and mapped QTL associated with hybrid male sterility. In both crosses, I identified a large set of autosomal and X-linked QTL associated with several hybrid male sterility traits, including testis weight, sperm density, and sperm morphology. In many cases, sterility was recessive at autosomal loci, highlighting the importance of reproductive barriers beyond the F1 generation in house mice. I also identified strong linkage of most hybrid male sterility traits to the pseudoautosomal region in the M. m. castaneus x M. m. domesticus intercross. I documented a pronounced shift of the M. m. castaneus pseudoautosomal region boundary and fine-mapped its location to ~430 kb proximal of the M. m. domesticus boundary. Combined, this represents a novel reproductive barrier between subspecies of house mice that may be a result of substantial divergence in the structure of this region. I compared QTL between the two intercrosses and found that three of the hybrid male sterility QTL were shared. These QTL offer promising avenues for identifying genes responsible for reproductive barriers between multiple subspecies pairs of house mice.