From Mice to Mutations: Genetic Basis of Adaptive Coloration in Peromyscus

Adaptation is a central focus in biology. However, understanding of the proximate and ultimate mechanisms of adaptive evolution is rarely accomplished in a single system.  Here, we describe both the molecular and evolutionary mechanisms responsible for cryptic coat color in deer mice (Peromyscus maniculatus) that have recently invaded the 8000-year-old pale soils of the Nebraska Sand Hills. First, we describe laboratory experiments that link genetic variation at the Agouti locus to multiple traits that contribute to the light appearance of Sand Hills mice. Next, we use a targeted enrichment strategy to genotype 90 mice from a phenotypically variable natural population at the 185-kb Agouti locus, as well as ~3000 additional 1.5-kb regions to control for demography. Fine-scale mapping of Agouti reveals a unique set of polymorphisms associated with each trait, thereby rejecting the hypothesis of a single pleiotropic mutation of large effect.  We then evaluate evidence for selection using both scans for molecular signatures of selection within a population and clinal analyses of phenotypes and genotypes in mice collected from multiple populations along a 350-km transect spanning the Sand Hills. These complementary analyses provide evidence for selection on light haplotypes and suggest that the strength of selection varies across the traits. Together, these data suggest that multiple mutations—each contributing to a distinct trait associated with the light phenotype—have been selected for cryptic coloration on the Sand Hills. Our results highlight the importance of carefully dissecting phenotypes and going beyond gene-level resolution when studying the genetic basis of adaptation.