Genomic insights into population stratification, biological adaptation, and archaic introgression at the crossroads of the Himalayas and lowland East Asia

Abstract

The Tibetan-Yi Corridor (TYC) has been a crucial agro-pastoral region in the eastern Himalayas, linking the Qinghai-Tibet Plateau with the lowlands of East Asia and facilitating human migration over millennia. Despite its significance, genomic research on TYC populations is limited, restricting understanding of their origins and health. We present genomic data from 1,031 individuals from Austroasiatic and Sino-Tibetan groups, including 147 whole-genome sequences from 13 underrepresented Tibeto-Burman and Austroasiatic communities. Our analysis uncovered approximately 3.3 million new genetic variants and identified four distinct genetic backgrounds among TYC populations. Demographic reconstructions highlight strong genetic connections among Tibeto-Burman groups, Central Plain Sinitic populations, and Yellow River Yangshao farmers, supporting a shared origin for Sino-Tibetan speakers. We observed signatures of high-altitude adaptation common with Tibetans and TYC-specific variants associated with pigmentation and hypoxia response. Differentiation involved mechanisms like HLA-DQB1-rs1049083, related to immune function. Certain rare pathogenic variants, such as CYP21A2-rs6467 and PRX-rs3814290, were especially frequent. Variants influencing warfarin sensitivity showed considerable variation. Archaic human introgression contributed to complexity, affecting cardiovascular and immune-related genes, indicative of adaptation through ancient human interactions. This research advances understanding of human evolution in this region and highlights the importance of broader genetic studies for insights into diversity and tailored medical approaches.