Meeting Abstract

P3-73   -   The contribution of allelic variation in Deptor to high elevation adaptation in deer mice Sleeting, MF*; Schweizer, RM; Wilsterman, K; Ivy, C; Scott, GR; Cheviron, ZA; University of Montana; University of Montana; University of Montana; McMaster University; McMaster University; University of Montana michael.sleeting@umconnect.umt.edu

Many species have adapted to high elevation through the convergent evolution of physiological phenotypes. The genetic bases of these adaptive modifications are not well understood, but genome scans have documented repeated selection on hypoxia-signaling genes in several high-elevation lineages. For example, allelic variation at Endothelial PAS Domain Protein 1 (Epas1) has been shown to contribute to differences in cardiopulmonary responses to hypoxia in highland and lowland populations of the North American deer mouse (Peromyscus maniculatus), and patterns of genetic variation suggest that this locus has experienced a history of spatially-varying selection. Hundreds of other genes in the P. maniculatus genome also exhibit similar signatures of selection, but the phenotypic effects of variants at these loci are unknown. One such locus is DEP Domain Containing mTOR Interacting Protein (Deptor). In mammals, the hypoxic chemoreflex is stimulated in part by glomus cells in the carotid body, and carotid body development is stimulated via mTOR growth signaling. Because Deptor is a known inhibitor of mTOR, we hypothesized that allelic variation at Deptor may contribute to documented differences in carotid body development and hypoxic ventilatory responses between highlanders and lowlanders. Using population genomic analyses of natural selection, we show that Deptor has experienced a history of natural selection at high-elevation. We then use experimental crosses of highland and lowland deer mice to isolate the phenotypic effects of Deptor genotype on carotid body development and ventilatory responses to hypoxia. In addition, because Epas1 has recently been shown to be critical to carotid body development under hypoxia, we test for interactions between Deptor and Epas1 genotypes to better understand the interactive effects of allelic variation at these loci. Together these results shed light on the genetic basis of complex and dynamic physiological traits.