Characterization of Structural Variation in Tibetans Reveals New Evidence of High-altitude Adaptation and Introgression

Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. To investigate the role of SVs in high-altitude adaptation (HAA), we here generated a comprehensive catalog of SVs in a Chinese Tibetan (n = 15) and Han (n = 10) population using the nanopore sequencing technology. Among a total of 38,216 unique SVs in the catalog, 27% were sequence-resolved for the first time. We systemically assessed the distribution of these SVs across repeat sequences and functional genomic regions. Through genotyping in additional 189 genomes, we identified 90 Tibetan-Han stratified SVs and 124 candidate adaptive genes. Besides, we discovered 15 adaptive introgressed SV candidates and provided evidence for a deletion of 335 base pairs at 1p36.32. Overall, our results highlight the important role of SVs in the evolutionary processes of Tibetans adaptation to the Qinghai-Tibet Plateau and provide a valuable resource for future HAA studies.