De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation
| Autor: | Xuebin Qi, Yongbo Guo, Bin Li, Zhilin Ning, Shuhua Xu, Yang Gao, Baimakangzhuo, Dejiquzong, Gonggalanzi, Xiaoji Wang, Shiming Liu, Tianyi Wu, Chaoying Cui, Ouzhuluobu, Wangshan Zheng, Lian Deng, Jun Li, Haiyi Lou, Duojizhuoma, Bing Su, Yaoxi He, Bianba, Caijuan Bai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
AcademicSubjects/SCI00010 Population Sequence assembly Biology 010603 evolutionary biology 01 natural sciences Genome 03 medical and health sciences genetic adaptation education Gene Denisovan reference genome 030304 developmental biology 0303 health sciences education.field_of_study Multidisciplinary Contig Molecular Biology & Genetics structural variants biology.organism_classification Evolutionary biology long-read sequencing Human genome AcademicSubjects/MED00010 Reference genome Research Article Tibetan |
| Zdroj: | National Science Review |
| ISSN: | 2053-714X 2095-5138 |
| Popis: | 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 (ZF1), 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 ZF1-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 of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (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. |
| Databáze: | OpenAIRE |
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