The genetic basis of reproductive isolation in house mice: Studies of a European hybrid zone

A complete understanding of the speciation process requires elucidation of the underlying genetic details. Considerable empirical and theoretical research has revealed two important patterns that characterize the genetic basis of reproductive isolation. First, reproductive isolation is usually caused by incompatible substitutions at different, interacting loci. Second, the locations of genes contributing to reproductive isolation are biased toward the X chromosome. These observations suggest that reproductive barriers between young species are frequently due to disrupted interactions involving genes on the X chromosome. This idea motivates a detailed study of introgression for X-linked loci across a European hybrid zone between two species of house mice, Mus domesticus and M. musculus (Appendix A). Allele frequency patterns at 13 molecular markers with known chromosomal positions identify one region with clearly reduced introgression. This piece of the X chromosome may contain genes that confer reproductive barriers between M. domesticus and M. musculus. Expected patterns of hybrid zone introgression for incompatible substitutions between the X chromosome and the autosomes are also investigated using computer simulations (Appendix B). The results indicate that both the locations and shapes of allele frequency clines are distorted by selection against hybrids, with effects related to the dominance of the interacting alleles and inheritance patterns of the X chromosome (hemizygosity). Additionally, loci closely linked to the targets of selection show only weak reductions in introgression, suggesting that neutral gene flow is not strongly impeded by selection against hybrids. Finally, the mouse genome sequence is used to compare patterns of hybrid zone introgression to several genomic attributes (Appendix C). No clear correlates of introgression emerge, suggesting that reproductive isolation between M. domesticus and M. musculus may involve a small number of genes with large effects. Using location in the X-linked region of reduced introgression, a high rate of protein evolution, and restricted expression in the male germ line as criteria, seven candidate genes for reproductive isolation are identified. These results underscore the value of studying natural patterns of introgression in model genetic organisms for understanding the genetic basis of speciation