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

Replicated 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 putatively regulatory regions. Genes that contained the most extreme outliers relate to traits such as body weight or size, metabolism, immunity, fat, eye function, and the cardiovascular system. We then compared these results with the results of analyses of published data 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. These genes are diverse, with functions relating to metabolism, immunity, cardiac function, and circadian rhythm, among others. We also found parallel shifts in allele frequency in candidate genes across latitudinal gradients. Finally, combining data from all three transects, we identified several genes associated with variation in body weight. Overall, our results provide strong evidence of shared responses to selection and identify 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 significant overlap of genes that show signals of selection. Here, we investigate the genetics of environmental adaptation in South America. We found that populations in South America are genetically distinct from populations in North America. We identified candidate genes for environmental adaptation with links to traits like body size, metabolism, immunity, eye function, thermoregulation and the cardiovascular system. We then bring together data from three transects across two continents to determine if environmental adaptation is predictable, with shared genetic responses. We found that most responses to selection do not involve changes in amino acid sequence and therefore are likely due to changes in gene regulation. We also found that while most candidate genes are unique to individual transects, there was more overlap than expected by chance. In addition, we observed parallel shifts in allele frequency among shared candidate genes, i.e., shifts in the same direction across different latitudinal gradients. These results suggest that there is a shared response to selection and identify a core set of candidate genes that likely contribute to environmental adaptation. Finally, we combine the data from all three transects to identify genes associated with variation in body weight. These findings highlight the value of studying wild populations of this important genetic model system. [ABSTRACT FROM AUTHOR]