Across two continents: the genomic basis of environmental adaptation in house mice (Mus musculus domesticus) from the Americas

Parallel clines across environmental gradients can be strong evidence of adaptation. House mice ( Mus musculus domesticus ) were introduced to the Americas by European colonizers and are now widely distributed from Tierra del Fuego to Alaska. Multiple aspects of climate, such as temperature, vary predictably across latitude in the Americas. Past studies of North American populations across latitudinal gradients provided evidence of environmental adaptation in traits related to body size, metabolism, and behavior and identified candidate genes using selection scans. Here, we investigate genomic signals of environmental adaptation on a second continent, South America, and ask whether there is evidence of parallel adaptation across multiple latitudinal transects in the Americas. We first identified loci across the genome showing signatures of selection related to climatic variation in mice sampled across a latitudinal transect in South America, accounting for neutral population structure. Consistent with previous results, most candidate SNPs were in regulatory regions. Genes containing the most extreme outliers relate to traits such as body weight or size, metabolism, immunity, fat, and development or function of the eye as well as traits associated with the cardiovascular and renal systems. We then combined these results with published results from two transects in North America. While most candidate genes were unique to individual transects, we found significant overlap among candidate genes identified independently in the three transects, providing strong evidence of parallel adaptation and identifying genes that likely underlie recent environmental adaptation in house mice across North and South America. Author summary Since their arrival with European colonizers, house mice have successfully spread throughout the Americas. There is strong evidence that populations in North America have adapted in that time, including parallel evolution of phenotypes across latitude (e.g., body size, behavior) as well as the identification of genes that show signals of selection. Here, we investigate the genetics of environmental adaptation in South America. We find that populations in South America evolve independently of populations in North America. We identify candidate genes for environmental adaptation with links to traits like body size, metabolism, immunity, eye function, and the cardiovascular and renal systems. We then bring together data from three transects across two continents to determine if environmental adaptation is predictable, with parallel genetic changes in response to shared conditions. We find that most evidence of environmental adaptation lies in regulatory regions and that, while most candidate genes are unique to individual transects, many are shared, providing significant evidence of parallel adaptation. We identify a core set of candidate genes independently identified in all three transects that likely contribute to environmental adaptation in the Americas. These results highlight the value of studying wild populations of this genetic model system. ### Competing Interest Statement The authors have declared no competing interest.