Structural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated.Here,combining long-read sequencing with multiple scaffolding techniques,we assembled a high-quality Tibetan genome (ZF 1),with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb.The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38).Markedly,we detected 17 900 SVs,among which the ZFl-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway.Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese.This deletion is significantly associated with lower systolic pulmonary arterial pressure,one of the key adaptive physiological traits in Tibetans.Moreover,with the use of the high-quality de novo assembly,we observed a much higher rate ofgenome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF 1 (1.32％-1.53％) compared to other East Asian genomes (0.70％-0.98％),reflecting a unique genomic composition of Tibetans.One such archaic hominid shared sequence-a 662-bp intronic insertion in the SCUBE2 gene-is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans.Collectively,we generated the first high-resolution Tibetan reference genome,and the identified SVs may serve as valuable resources for future evolutionary and medical studies.