Genomic insight into the population history and biological adaptations of High-Altitude Tibetan highlanders in Nagqu

Tibetan, one of the largest indigenous populations living in the high-altitude region of the Tibetan Plateau (TP), has developed a suite of physiological adaptation strategies to cope with the extreme highland environment in TP. To comprehensively characterize the genetic origin and detailed evolutionary profiles of Tibetan highlanders, here, we reported genome-wide SNP data from 62 Nagqu Tibetans who belong to U-Tsang Tibetan groups but speak Kham Tibetan dialect, and analyzed  together with published data from 1,067 individuals in 167 modern and ancient populations. Overall, patterns of alleles sharing suggested (1) the relatively genetic homogeny between studied Nagqu Tibetans and published U-Tang Tibetans from Lhasa, Nagqu, Shannan, and Shigatse, as well as ancient Nepals; (2) the genomic connection between lowland present-day northern Han Chinese/ancient millet farmers and highland Tibetans. The IBD sharing profiles validated the shared demographic history between Kham-speaking Tibetans and U-Tsang Tibetans as well as Kham-speaking Chamdo Tibetans. The fitted qpAdm models showed that studied Tibetans could be fitted as having the main ancestry from late Neolithic upper Yellow River Qijia millet farmers and deep ancestries from Southern East Asians, with a non-neglectable western Steppe-related ancestry (~3%). We further scanned the selection-candidate genomic regions via iHS and XP-EHH tests based on two different SNP panels and identified several putative genomic candidate genes associated with essential human biological functions such as immune response, enzyme activity, signal transduction.