Cargando…
EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses
High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole a...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805228/ https://www.ncbi.nlm.nih.gov/pubmed/31273382 http://dx.doi.org/10.1093/molbev/msz158 |
_version_ | 1783461333298053120 |
---|---|
author | Liu, Xuexue Zhang, Yanli Li, Yefang Pan, Jianfei Wang, Dandan Chen, Weihuang Zheng, Zhuqing He, Xiaohong Zhao, Qianjun Pu, Yabin Guan, Weijun Han, Jianlin Orlando, Ludovic Ma, Yuehui Jiang, Lin |
author_facet | Liu, Xuexue Zhang, Yanli Li, Yefang Pan, Jianfei Wang, Dandan Chen, Weihuang Zheng, Zhuqing He, Xiaohong Zhao, Qianjun Pu, Yabin Guan, Weijun Han, Jianlin Orlando, Ludovic Ma, Yuehui Jiang, Lin |
author_sort | Liu, Xuexue |
collection | PubMed |
description | High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski’s horses added for comparison. We find that Tibetan horses do not descend from Przewalski’s horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages. |
format | Online Article Text |
id | pubmed-6805228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68052282019-10-25 EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses Liu, Xuexue Zhang, Yanli Li, Yefang Pan, Jianfei Wang, Dandan Chen, Weihuang Zheng, Zhuqing He, Xiaohong Zhao, Qianjun Pu, Yabin Guan, Weijun Han, Jianlin Orlando, Ludovic Ma, Yuehui Jiang, Lin Mol Biol Evol Discoveries High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski’s horses added for comparison. We find that Tibetan horses do not descend from Przewalski’s horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages. Oxford University Press 2019-11 2019-07-04 /pmc/articles/PMC6805228/ /pubmed/31273382 http://dx.doi.org/10.1093/molbev/msz158 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Discoveries Liu, Xuexue Zhang, Yanli Li, Yefang Pan, Jianfei Wang, Dandan Chen, Weihuang Zheng, Zhuqing He, Xiaohong Zhao, Qianjun Pu, Yabin Guan, Weijun Han, Jianlin Orlando, Ludovic Ma, Yuehui Jiang, Lin EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title | EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title_full | EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title_fullStr | EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title_full_unstemmed | EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title_short | EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses |
title_sort | epas1 gain-of-function mutation contributes to high-altitude adaptation in tibetan horses |
topic | Discoveries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805228/ https://www.ncbi.nlm.nih.gov/pubmed/31273382 http://dx.doi.org/10.1093/molbev/msz158 |
work_keys_str_mv | AT liuxuexue epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT zhangyanli epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT liyefang epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT panjianfei epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT wangdandan epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT chenweihuang epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT zhengzhuqing epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT hexiaohong epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT zhaoqianjun epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT puyabin epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT guanweijun epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT hanjianlin epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT orlandoludovic epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT mayuehui epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses AT jianglin epas1gainoffunctionmutationcontributestohighaltitudeadaptationintibetanhorses |