“Detecting past and Ongoing Natural Selection among Ethnically Tibetan Women at High Altitude in Nepal”, 2018-08-21 (; similar):
Adaptive evolution in humans has rarely been characterized for its whole set of components, ie. selective pressure, adaptive phenotype, beneficial alleles and realized fitness differential. We combined approaches for detecting polygenic adaptations and for mapping the genetic bases of physiological and fertility phenotypes in ~1000 indigenous ethnically Tibetan women from Nepal, adapted to high altitude. The results of genome-wide association analyses and tests for polygenic adaptations showed evidence of positive selection for alleles associated with more pregnancies and live births and evidence of negative selection for those associated with higher offspring mortality. Lower hemoglobin level did not show clear evidence for polygenic adaptation, despite its strong association with an EPAS1 haplotype carrying selective sweep signals.
Author Summary: The adaptations to high altitude environments in Tibetan populations have long been highlighted as an important case study of adaptive evolution in our species. Recent genetic studies found two genes, EGLN1 and EPAS1, the genetic variants in which were swept to high frequency in Tibetans due to strong positive natural selection. However, it still remains unclear if and how these and other genetic variants are connected to adaptive phenotypes and ultimately to fitness advantage. In this study, we collected genotype and phenotype information of 1,000 ethnically Tibetan women from the high Himalayan valleys in Nepal. Using both genome-wide association analysis and test for polygenic adaptations, we show that natural selection systematically altered frequency of alleles associated with reproductive outcomes to the direction of increasing fitness. That is, alleles associated with more pregnancies and live births, as well as those associated with lower offspring mortality, were under positive selection. Omitting the EPAS1 haplotype under selective sweep, the other variants associated with lower hemoglobin did not collectively show a clear signal for polygenic adaptation. Our study highlights the polygenic nature of human adaptive traits.