Tracing the evolution of human polygenic adaptive traits using high-resolution genomic data

It is well established that the ancestors of modern human populations have been exposed to multiple selective pressures during their migrations across the globe. This led different Homo sapiens populations to evolve local genetic adaptations, which enabled our species to thrive in diverse environmental settings. Nevertheless, the genetic bases of polygenic/complex adaptive traits, which are supposed to be responsible for the evolution of rapid adaptations, are still understudied due to the lack of proper methodological approaches. Here, we set up and fine-tuned a pipeline of analyses aimed at detecting genomic signatures ascribable to polygenic adaptations, which enabled the identification of functionally related gene networks pervasively targeted by the action of natural positive selection. The reliability of such integrated approach was tested on a large panel of whole genome sequence data belonging to several world-wide populations. Among the most compelling results, we detected polygenic selection signatures at loci modulating immune reactions of West Africans to endemic infections (e.g. VTN), and regulating cold-induced physiological responses in Eurasians (e.g. THRB) and Native Americans (e.g. IRS1), which also potentially led to dis-adaptations in some ethnic groups form the latter genetic cluster due to recent environmental/dietary shifts. Moreover, polygenic bases of adaptations to hypobaric hypoxia were explored by detecting novel patterns of Denisovan adaptive introgression in a Tibetan population and genomic signatures of convergent evolution between Himalayan and Andean high-altitude populations involving pathways with pro-angiogenic/cardiovascular protective roles. Signatures of adaptive introgression were detected in the Siberian Yakut population as well and were found to have shaped their cold-induced adaptive responses mediated by insulin/lipid metabolisms. Overall, the present thesis proposes an alternative methodological workflow to investigate the evolution of human polygenic adaptations and provides new insights into the complex genetic architecture of adaptive traits evolved by our species to cope with a multitude of selective pressures.