Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions

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Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.Different species have often evolved from a common ancestor. In order to become distinct species, however, the different groups of descendants of that ancestor must have become isolated from one another at some point in their history so that they could no longer mate or reproduce. For example, a mountain or a river might create a physical barrier that keeps species apart, so that if the species meet up again they may struggle to mate or produce offspring. Furthermore, any ‘hybrid’ offspring that are produced may themselves struggle to survive or successfully reproduce.Examining the genes of the hybrid offspring that result when two recently separated species crossbreed could help us to understand how new species evolve. However, the challenges of finding enough suitable hybrids to compare means that few studies have so far investigated the genetic changes that occur to make reproduction between separate species difficult.Two subspecies of the house mouse—Mus musculus musculus and Mus musculus domesticus—live alongside each other in a region of central Europe and can mate and produce hybrid offspring. Male hybrid mice are commonly less fertile than non-hybrids; this acts as a barrier to reproductive success that helps to maintain the separation between the two subspecies.Turner and Harr captured wild hybrid mice, bred them in the laboratory, and studied their offspring. This strategy enabled them to measure fertility in mice very similar to wild-caught hybrids, but now all individuals can be measured at the same age and under the same environmental conditions.A method called a genome-wide association study can be used to survey the genes of individuals with a particular disease or physical characteristic in an effort to identify gene variants that are associated with that condition. In many species, the weight of a male's testes has been linked to their fertility—small testes mean the male is likely to be less fertile. Changes in how genes are ‘expressed’ in the testes can also reduce fertility.Turner and Harr used a genome-wide association study to investigate which genetic changes are linked to changes in testis weight or how genes in the testes are expressed in the offspring of hybrid mice. This revealed that many separate genetic regions are involved; including some that had not previously been identified. Turner and Harr then examined how these gene regions interact with each other. With the exception of one gene, all interacted with at least one of the other genetic regions that had been identified, forming a complex network of interactions.Although a genome-wide association study reveals which genes are altered in hybrid mice with small testes, it does not reveal which of these genes actually cause the changes in testis size and gene expression. However, the work of Turner and Harr greatly narrows down the candidates for further investigation.




Turner, L. M., & Harr, B. (2014). Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions. ELife, 3.

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