Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes

Altitude adaptation is a complex process involving multiple physiological and biochemical responses to hypoxia and other environmental stresses. In-depth genetic analysis of Tibetan sheep, which exhibit significant adaptations to high-altitude hypoxia, promises to elucidate hypoxia-tolerance mechani...

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Main Authors: Yufang Song, Chao Yuan, Tingting Guo, Bowen Chen, Fan Wang, Zengkui Lu, Jianbin Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1632017/full
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author Yufang Song
Yufang Song
Chao Yuan
Chao Yuan
Tingting Guo
Tingting Guo
Bowen Chen
Bowen Chen
Fan Wang
Zengkui Lu
Zengkui Lu
Jianbin Liu
Jianbin Liu
author_facet Yufang Song
Yufang Song
Chao Yuan
Chao Yuan
Tingting Guo
Tingting Guo
Bowen Chen
Bowen Chen
Fan Wang
Zengkui Lu
Zengkui Lu
Jianbin Liu
Jianbin Liu
author_sort Yufang Song
collection DOAJ
description Altitude adaptation is a complex process involving multiple physiological and biochemical responses to hypoxia and other environmental stresses. In-depth genetic analysis of Tibetan sheep, which exhibit significant adaptations to high-altitude hypoxia, promises to elucidate hypoxia-tolerance mechanisms in plateau animals. Here, we conducted a genome-wide selection scan on three Tibetan sheep populations: low-altitude Tao (TS; 2887 m), medium-altitude Tianjun white (WT; 3331 m), and high-altitude Huoerba (HB; 4614 m). Using the population differentiation index (Fst) and nucleotide diversity (θπ) ratio, we analyzed selection signals associated with hypoxia at high-altitudes. We screened 865, 941, and 876 candidate genes in the TS vs. WT, TS vs. HB, and WT vs. HB group comparisons, respectively, 55 of which were jointly screened. Integrated analysis further identified several key pathways and genes under positive selection in Tibetan sheep populations, including metabolic pathways (GSTA1, ALAS1, HMOX2, SCD, ME1, ACSL6, PIK3C2G), melanogenesis (MITF, EP300), and the HIF-1 signaling pathway (ERBB2, HIF1A, RELA). Among these, the metabolic pathways may enhance energy production under hypoxic conditions, while melanogenesis and the HIF-1 signaling pathway are likely associated with ultraviolet radiation protection and hypoxia tolerance, respectively. This study provides valuable insights into the genetic mechanism of high-altitude adaptation in Tibetan sheep, and also provides important theoretical basis for the conservation and breeding of Tibetan sheep and the sustainable development of plateau animal husbandry.
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spelling doaj-art-bbb0c3e8c55e4cfa9f59c2ee22a1b2ab2025-08-20T03:36:45ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-08-011210.3389/fvets.2025.16320171632017Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudesYufang Song0Yufang Song1Chao Yuan2Chao Yuan3Tingting Guo4Tingting Guo5Bowen Chen6Bowen Chen7Fan Wang8Zengkui Lu9Zengkui Lu10Jianbin Liu11Jianbin Liu12Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaKey Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaKey Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaKey Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaCollege of Life Science and Engineering, Northwest Minzu University, Lanzhou, ChinaKey Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaKey Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaSheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, ChinaAltitude adaptation is a complex process involving multiple physiological and biochemical responses to hypoxia and other environmental stresses. In-depth genetic analysis of Tibetan sheep, which exhibit significant adaptations to high-altitude hypoxia, promises to elucidate hypoxia-tolerance mechanisms in plateau animals. Here, we conducted a genome-wide selection scan on three Tibetan sheep populations: low-altitude Tao (TS; 2887 m), medium-altitude Tianjun white (WT; 3331 m), and high-altitude Huoerba (HB; 4614 m). Using the population differentiation index (Fst) and nucleotide diversity (θπ) ratio, we analyzed selection signals associated with hypoxia at high-altitudes. We screened 865, 941, and 876 candidate genes in the TS vs. WT, TS vs. HB, and WT vs. HB group comparisons, respectively, 55 of which were jointly screened. Integrated analysis further identified several key pathways and genes under positive selection in Tibetan sheep populations, including metabolic pathways (GSTA1, ALAS1, HMOX2, SCD, ME1, ACSL6, PIK3C2G), melanogenesis (MITF, EP300), and the HIF-1 signaling pathway (ERBB2, HIF1A, RELA). Among these, the metabolic pathways may enhance energy production under hypoxic conditions, while melanogenesis and the HIF-1 signaling pathway are likely associated with ultraviolet radiation protection and hypoxia tolerance, respectively. This study provides valuable insights into the genetic mechanism of high-altitude adaptation in Tibetan sheep, and also provides important theoretical basis for the conservation and breeding of Tibetan sheep and the sustainable development of plateau animal husbandry.https://www.frontiersin.org/articles/10.3389/fvets.2025.1632017/fullTibetan sheephigh-altitude adaptationwhole-genome resequencingFstθπ ratioselection signal
spellingShingle Yufang Song
Yufang Song
Chao Yuan
Chao Yuan
Tingting Guo
Tingting Guo
Bowen Chen
Bowen Chen
Fan Wang
Zengkui Lu
Zengkui Lu
Jianbin Liu
Jianbin Liu
Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
Frontiers in Veterinary Science
Tibetan sheep
high-altitude adaptation
whole-genome resequencing
Fst
θπ ratio
selection signal
title Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
title_full Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
title_fullStr Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
title_full_unstemmed Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
title_short Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes
title_sort genome wide selection signal analysis reveals the adaptability of tibetan sheep to high altitudes
topic Tibetan sheep
high-altitude adaptation
whole-genome resequencing
Fst
θπ ratio
selection signal
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1632017/full
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