Desert adaptation in house mice

House mice (Mus musculus domesticus) are native to Europe and have recently been introduced to habitats around the world in association with humans. Here we ask whether mice from the Sonoran desert show phenotypic and regulatory divergence associated with living in a water-limited environment and whether this variation reflects an evolved or plastic response. First, we demonstrate that lab-born descendants of wild-caught mice from Tucson drink significantly less water than mice from other localities in the Americas. Next, we compared the response of Tucson mice and mice from a non-xeric environment to water restriction on the organismal and transcriptional level. Consistent with our hypothesis that Tucson mice have adapted to water restricted desert living, we find that Tucson mice (1) lose less weight under water-stress, (2) show differences in blood chemistry related kidney function, and (3) show reduced plastic responses in kidney expression when compared to non-xeric mice. Further, we find that non-xeric mice generally show shifts towards Tucson-like expression under water stress, suggesting that the plastic response to water stress in house mice represents an example adaptive plasticity. Finally, we identify several candidate genes for adaptation to the Sonoran Desert, including Aqp1 and solute carriers. Our findings demonstrate strong evidence for local adaptation in an introduced generalist and suggest a role for adaptive plasticity in the colonization of the Sonoran Desert environment.