Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep

文献类型： 外文期刊

第一作者： Li, Chao

作者： Li, Chao;Chen, Bingchun;Zhou, Shiwei;Kalds, Peter;Zhang, Ke;Huang, Shuhong;Li, Ran;Li, Yan;Fang, Wenwen;Cai, Yudong;Jiang, Yu;Chen, Yulin;Wang, Xiaolong;Li, Chao;Bhati, Meenu;Leonard, Alexander;Pausch, Hubert;Langda, Suo;Cuoji, Awang;Wu, Yujiang;Cuomu, Renqin;Gui, Ba;Pu, Peng;Zhu, Xiaojia;Wang, Xiran;Zhu, Haolin;Li, Ming;Wang, Yutao;Jia, Ting;Pu, Tianchun;Pan, Xiangyu;He, Chong;Zhou, Ping;Zhou, Ping;Han, Jian-Lin;Han, Jian-Lin

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关键词： Environmental adaptation; High altitude; Hypoxia; Selection signature; Sheep

期刊名称：GENOMICS PROTEOMICS & BIOINFORMATICS （ 影响因子：11.5； 五年影响因子：10.3 ）

ISSN： 1672-0229

年卷期： 2024 年 22 卷 2 期

页码：

收录情况： SCI

摘要： Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing similar to 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated beta-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

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