Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

BACKGROUND: Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little is known of adaptive introgressed SVs in Tibetans so far. RESULTS: Here, we generate a comprehensive catalog of SVs in a Chinese Tibetan (n = 15) and Han (n = 10) population using nanopore sequencing technology. Among a total of 38,216 unique SVs in the catalog, 27% are sequence-resolved for the first time. We systematically assess the distribution of these SVs across repeat sequences and functional genomic regions. Through genotyping in additional 276 genomes, we identify 69 Tibetan-Han stratified SVs and 80 candidate adaptive genes. We also discover a few adaptive introgressed SV candidates and provide evidence for a deletion of 335 base pairs at 1p36.32. CONCLUSIONS: 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 high-altitude adaptation studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02382-3.