One of the greatest challenges modern humans faced as they migrated into Eurasia was a cold climate. This was especially true of Siberia, where mean January temperatures of -40ºC are common and temperatures of -70ºC have been recorded. Humans adapted to this environment in multiple ways, but the role of genetic adaptation has been unclear. In this dissertation, I address this question with large-scale genomic data, and statistical and informatics-based methods designed to find ``signals of selection". Using this approach, I find strong evidence of positive natural selection acting on missense variants in three genes, PLA2G2A, PLIN1 and ANGPTL8, all with essential functions in lipid metabolism and brown adipose tissue function. In addition, I find strong support for the adaptive introgression of a small region on chromosome 1 from a Denisovan-like archaic hominid into modern humans. This region appears to have introgressed in Central Siberia and then later spread into Europe and the New World. Lastly, I advance the hypothesis that these adaptive variants are related to the very low breast cancer rate found in many traditional circumpolar populations. Molecular evidence indicates these same genes play important roles in breast tumor growth and proliferation, and these variants may confer a protective phenotype. Together these findings illustrate how local adaptation to climate and diet can lead to changes in metabolic function and disease susceptibility
