Ancestral origins and post-admixture adaptive evolution of highland Tajiks

It remains debatable how many genes and how various the mechanisms are behind human adaptation to extreme environments, such as high altitudes. Despite extensive studies on Tibetans, Andeans and Ethiopians, new insights are expected to be provided with careful analysis of underrepresented highlanders living in a different geographical region, such as the Tajiks, who reside on the Pamir Plateau at an average altitude exceeding 4000 meters. Moreover, genetic admixture, as we observed in the current whole-genome deep-sequencing study of Xinjiang Tajiks (XJT), offers a unique opportunity to explore how admixture may facilitate adaptation to high-altitude environments. Compared with other extensively studied highlanders, XJT showed pronounced admixture patterns: most of their ancestry are derived from West Eurasians (34.5%-48.3%) and South Asians (21.4%-40.0%), and some minor ancestry from East Asians and Siberians (3.62%-17.5%). The greater genetic diversity in XJT than in their ancestral source populations provides a genetic basis for their adaptation to high-altitude environments. The admixture gain of functional adaptive components from ancestral populations could facilitate adaptation to high-altitude environments. Specifically, admixture-facilitated adaptation was strongly associated with skin-related candidate genes that respond to UV radiation (e.g. HERC2 and BNC2) and cardiovascular-system-related genes (e.g. MPI and BEST1). Notably, no adaptive variants of genes showing outstanding natural selection signatures in the Tibetan or Andean highlanders were identified in XJT, including EPAS1 and EGLN1, indicating that a different set of genes contributed to XJT's survival on the Pamir Plateau, although some genes underlying natural selection in XJT have been previously reported in other highlanders. Our results highlight the unique genetic adaptations in XJT and propose that admixture may play a vital role in facilitating high-altitude adaptation. By introducing and elevating diversity, admixture likely induces novel genetic factors that contribute to the survival of populations in extreme environments like the highlands.