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, Chao Li International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Bingchun Chen International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Suo Langda Institute of Animal Science, Tibet Academy of Agricultural and Animal Husbandry Sciences , Lhasa 850009, China Search for other works by this author on: Oxford Academic Peng Pu School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University , Lanzhou 730070, China Search for other works by this author on: Oxford Academic Xiaojia Zhu College of Life Sciences, Shaanxi Normal University , Xi’an 710119, China Search for other works by this author on: Oxford Academic Shiwei Zhou International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Peter Kalds International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Ke Zhang International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Meenu Bhati Animal Genomics, ETH Zürich , Zürich 8092, Switzerland Search for other works by this author on: Oxford Academic Alexander Leonard Animal Genomics, ETH Zürich , Zürich 8092, Switzerland Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0002-2769-7616 , Shuhong Huang International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Ran Li International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Awang Cuoji Institute of Animal Science, Tibet Academy of Agricultural and Animal Husbandry Sciences , Lhasa 850009, China Search for other works by this author on: Oxford Academic Xiran Wang College of Life Sciences, Shaanxi Normal University , Xi’an 710119, China Search for other works by this author on: Oxford Academic Haolin Zhu College of Life Sciences, Shaanxi Normal University , Xi’an 710119, China Search for other works by this author on: Oxford Academic Yujiang Wu Institute of Animal Science, Tibet Academy of Agricultural and Animal Husbandry Sciences , Lhasa 850009, China Search for other works by this author on: Oxford Academic Renqin Cuomu Institute of Animal Science, Tibet Academy of Agricultural and Animal Husbandry Sciences , Lhasa 850009, China Search for other works by this author on: Oxford Academic Ba Gui Institute of Animal Science, Tibet Academy of Agricultural and Animal Husbandry Sciences , Lhasa 850009, China Search for other works by this author on: Oxford Academic Ming Li Zoology and Evolutionary Biology, Department of Biology, University of Konstanz , Konstanz 78457, Germany Search for other works by this author on: Oxford Academic Yutao Wang College of Life and Geographic Sciences, Kashi University , Kashi 844000, China Search for other works by this author on: Oxford Academic Yan Li International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Wenwen Fang International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Ting Jia Beijing Key Laboratory of Captive Wildlife Technologies , Beijing Zoo, Beijing 100044, China Search for other works by this author on: Oxford Academic Tianchun Pu Beijing Key Laboratory of Captive Wildlife Technologies , Beijing Zoo, Beijing 100044, China Search for other works by this author on: Oxford Academic Xiangyu Pan Department of Medical Research, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences , Guangzhou 510080, China Search for other works by this author on: Oxford Academic Yudong Cai International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Chong He Key Laboratory of Agricultural Internet of Things, Ministry of Agriculture and Rural Affairs/Shaanxi Key Laboratory of Agricultural Information Perception and Intelligent Service, College of Information Engineering, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Liming Wang Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Sciences , Shihezi 832000, China State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Sciences , Shihezi 832000, China Search for other works by this author on: Oxford Academic Yu Jiang International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Jian-Lin Han CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS) , Beijing 100193, China Livestock Genetics Program, International Livestock Research Institute (ILRI) , Nairobi 00100, Kenya Search for other works by this author on: Oxford Academic Yulin Chen International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Search for other works by this author on: Oxford Academic Ping Zhou Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Sciences , Shihezi 832000, China State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Sciences , Shihezi 832000, China Corresponding authors. E-mail: xiaolongwang@nwafu.edu.cn (Wang X), hubert.pausch@usys.ethz.ch (Pausch H), zhpxqf@163.com (Zhou P). Search for other works by this author on: Oxford Academic Hubert Pausch Animal Genomics, ETH Zürich , Zürich 8092, Switzerland Corresponding authors. E-mail: xiaolongwang@nwafu.edu.cn (Wang X), hubert.pausch@usys.ethz.ch (Pausch H), zhpxqf@163.com (Zhou P). Search for other works by this author on: Oxford Academic Xiaolong Wang International Joint Agriculture Research Center for Animal Bio-Breeding, Ministry of Agriculture and Rural Affairs/Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University , Yangling 712100, China Corresponding authors. E-mail: xiaolongwang@nwafu.edu.cn (Wang X), hubert.pausch@usys.ethz.ch (Pausch H), zhpxqf@163.com (Zhou P). Search for other works by this author on: Oxford Academic
Chao Li, Bingchun Chen, Suo Langda, Peng Pu Equal contribution.
Author Notes
Genomics, Proteomics & Bioinformatics, qzae030, https://doi.org/10.1093/gpbjnl/qzae030
Published:
02 April 2024
Article history
Received:
28 September 2023
Revision received:
09 January 2024
Accepted:
29 February 2024
Published:
02 April 2024
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Chao Li, Bingchun Chen, Suo Langda, Peng Pu, Xiaojia Zhu, Shiwei Zhou, Peter Kalds, Ke Zhang, Meenu Bhati, Alexander Leonard, Shuhong Huang, Ran Li, Awang Cuoji, Xiran Wang, Haolin Zhu, Yujiang Wu, Renqin Cuomu, Ba Gui, Ming Li, Yutao Wang, Yan Li, Wenwen Fang, Ting Jia, Tianchun Pu, Xiangyu Pan, Yudong Cai, Chong He, Liming Wang, Yu Jiang, Jian-Lin Han, Yulin Chen, Ping Zhou, Hubert Pausch, Xiaolong Wang, Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep, Genomics, Proteomics & Bioinformatics, 2024;, qzae030, https://doi.org/10.1093/gpbjnl/qzae030
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Abstract
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-Tibetan 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 ∼ 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 β-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. Of which, the haplotype A carried two hom*ologous 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 the haplotype A had an increased hemoglobin (Hb)–O2 affinity compared to those carrying the haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed a 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.
Environmental adaptation, High altitude, Hypoxia, Selection signature, Sheep
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Author notes
Chao Li, Bingchun Chen, Suo Langda, Peng Pu Equal contribution.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation and Genetics Society of China.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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