Adaptation to Climate and Susceptibility Genes for Diseases of Global Significance

Modern humans evolved in Africa around 100-200 kya, and since then human populations have expanded and diversified to occupy an exceptionally broad range of habitats and climates and to use a variety of subsistence modes and dietary components. Adaptations to these different aspects of the environment are evident in the geographic distributions of many traits.  For example, significant correlations exist between body mass and temperature, and there is evidence, from studies of arctic populations, that human metabolism has been shaped by adaptations to cold stress.  Like body mass, variation in skin pigmentation is strongly correlated with climate and geography, i.e. distance from the equator and solar radiation, likely as a result of selective pressures acting to maintain appropriate levels of vitamin D and folates. Studies of candidate genes support roles for selection on energy metabolism, sodium homeostasis, and the capacity to digest lactose from milk and starch from plants. These examples advance a model where exposures to new or intensified selective pressures resulted in physiological specializations.

Detection of beneficial alleles that evolved under selective pressures related to climate, diet and subsistence may be achieved by considering simultaneously the spatial distributions of the allele frequencies and of specific aspects of human environments. We have developed an approach that allows scanning the human genome for signals of genetic adaptations to different environmental factors.  This approach, applied to a worldwide sample of human populations, identified many alleles that exhibit subtle, but concordant changes in frequencies across populations that live in the same geographic region, but that differ in terms of climate, ecoregion, main dietary component or mode of subsistence. Among these alleles, we found many in genes involved in pigmentation and immune response as well as in pathways related to starch and sucrose metabolism, energy metabolism, UV radiation, infection and immunity, and cancer. Among the strongest signals, we also find several alleles that overlap with those from recent genome-wide association studies, including polymorphisms associated with pigmentation, autoimmune diseases, lipid levels and type 2 diabetes. Therefore, to the extent that genetic factors contribute to health disparities, it may be speculated that adaptations to different environments may have played a role in shaping the different disease susceptibility across human populations.