%0 Journal Article %J Molecular Biology and Evolution %D 2018 %T The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow. %A Pfeifer, SP %A Laurent, S %A Sousa, VC %A Linnen, C. R. %A Foll, M %A Excoffier, L %A Hoekstra, HE %A Jensen, J. D. %X The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight into the conditions under which such a beneficial allele may be maintained, lost, or fixed. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 670,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, we observe strong haplotype structure around putatively beneficial mutations within the Agouti locus, and these mutations are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration. We discuss these empirical results in light of theoretical expectations, thereby providing a complete example of the dynamics between ancestral gene flow and local adaptation in a classic mammalian system. %B Molecular Biology and Evolution %V 35 %P 792-806 %G eng