Genetic adaptations to the environment in human populations

In this dissertation, I describe several studies that aim to clarify the role that the environment has played in shaping human genetic variation. In chapter 2, I examine variation in three uncoupling proteins (UCPs) -- one with a well-established role in non-shivering thermogenesis and two with hypothesized roles in this process -- to test the hypothesis that single nucleotide polymorphisms (SNPs) associated with increased expression of these proteins are more common in populations that are exposed to colder winter climate compared to populations in warmer climates. The results show evidence of spatially varying selection at UCP1 and UCP3 and suggest a role for UCP3 in cold tolerance. In chapter 3, I assess evidence of selection on the energy metabolism pathway as a whole, by selecting 82 metabolism candidate genes using a network-based approach and calculating correlations with climate for tagging SNPs genotyped across these genes in 54 worldwide populations. The results of this analysis show an enrichment of signal in metabolism genes relative to SNPs genotyped in control regions. In chapter 4, I use genome-wide genotype data for 61 worldwide populations to assess evidence of natural selection related to the environment. There is an enrichment of signal for nonsynonymous SNPs and SNPs near genes relative to SNPs far from genes for climate, subsistence and ecoregion. Among the SNPs and pathways with the strongest signals are several involved in pigmentation, immune response and metabolism. Taken together, the results of these projects suggest that spatially varying selection related to climate and subsistence has been an important force in shaping genetic variation across the human genome.