Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle

Xiaoting Xia; Fuwen Wang; Xiaoyu Luo; Shuang Li; Yang Lyu; Yining Zheng; Zhijie Ma; Kaixing Qu; Rende Song; Jianyong Liu; Jicai Zhang; Basang Wangdui; Basang Zhuzha; Suolang Quji; Li Zhao; Silang Wangmu; Ciren Luobu; Nima Cangjue; Danzeng Luosang; Suolang Sizhu; Haijian Cheng; Ruizhe Li; Zhipeng Wu; Ruihua Dang; Yongzhen Huang; Xianyong Lan; Luohao Xu; Haifei Hu; WaiYee Low; Zhuqing Zheng; Yu Wang; Yuanpeng Gao; Lu Deng; Johannes A Lenstra; Jianlin Han; Xueyi Yang; Wenfa Lyu; Bizhi Huang; Chuzhao Lei; Ningbo Chen

doi:10.1002/advs.202503258

Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle

Xiaoting Xia, Fuwen Wang, Xiaoyu Luo, Shuang Li, Yang Lyu, Yining Zheng, Zhijie Ma, Kaixing Qu, Rende Song, Jianyong Liu, Jicai Zhang, Basang Wangdui, Basang Zhuzha, Suolang Quji, Li Zhao, Silang Wangmu, Ciren Luobu, Nima Cangjue, Danzeng Luosang, Suolang SizhuHaijian Cheng, Ruizhe Li, Zhipeng Wu, Ruihua Dang, Yongzhen Huang, Xianyong Lan, Luohao Xu, Haifei Hu, WaiYee Low, Zhuqing Zheng, Yu Wang, Yuanpeng Gao, Lu Deng, Johannes A Lenstra, Jianlin Han, Xueyi Yang, Wenfa Lyu^*, Bizhi Huang, Chuzhao Lei, Ningbo Chen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Structural variations (SVs) play crucial roles in the evolutionary adaptation of domesticated animals to natural and human-controlled environments, but SVs have not been explored in Tibetan cattle, which recently migrated and rapidly adapted to the high altitudes of the Qinghai-Tibetan Plateau (QTP). In this study, a de novo chromosome-level genome assembly for Tibetan cattle is constructed. It is found that using a lineage-specific reference genome significantly increased variant detection accuracy and completeness. Analysis of long-read sequencing data from 36 high-altitude QTP and 48 low-altitude cattle identified 222 528 SVs and 259 SV hotspot regions. Positively selected SVs in high-altitude cattle are related to energy metabolism erythropoiesis and angiogenesis, and peroxisomal metabolism. A 102-bp intronic deletion in GNPAT likely upregulated its expression. It is distinguished 7293 SVs that may be introgressed from yak, including variants upstream of the hypoxia-inducing gene EGLN1. Finally, a ≈2-Mb heterozygous inversion and two translocations on chromosome 6 are likely associated with the cattle gray coat via regulatory effects on the KIT gene. The results confirm the importance of SVs in evolutionary adaptation and the contribution yak-introgressed SVs to the rapid acclimatization of QTP cattle.

Original language	English
Article number	e03258
Number of pages	17
Journal	Advanced Science
DOIs	https://doi.org/10.1002/advs.202503258
Publication status	E-pub ahead of print - 5 Jun 2025

Bibliographical note

Funding

This work was supported by the National Key R&D Program of China (2021YFF1001000 and 2021YFD1200400), the National Natural Science Foundation of China (32372854, 32341054, 32102523 and 32260823), the Key Research and Development Program of Xizang Autonomous Region of China (XZ202301ZY0008N), the Yunnan Expert Workstations (202305AF150156), the China Agriculture Research System of MOF and MARA (CARS-37), the Postdoctoral Fellowship Program of CPSF (GZC20232149), the Postdoctoral Research Project Funding of Shaanxi Province (2023BSHEDZZ132), the Open Project of State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University (2024-KF-02), the Program of Yunling Scholar and Yunling Cattle Special Program of Yunnan Joint Laboratory of Seeds and Seeding Industry (202205AR070001), the Construction of Yunling Cattle Technology Innovation Center and Industrialization of Achievements (2019ZG007), and Chuxiong Science and Technology Leading Talents (CXKJLJRC2023-07). The authors thank Lijing Tang and Yafei Mao for their valuable suggestions, and the High-Performance Computing (HPC) of Northwest A&F University (NWAFU) for providing the computing resources.

Funders	Funder number
National Key Research and Development Program of China	2021YFF1001000, 2021YFD1200400
National Key R&D Program of China	32372854, 32341054, 32102523, 32260823
National Natural Science Foundation of China	XZ202301ZY0008N
Key Research and Development Program of Xizang Autonomous Region of China	202305AF150156
Yunnan Expert Workstations	CARS-37
China Agriculture Research System of MOF	GZC20232149
Postdoctoral Fellowship Program of CPSF	2023BSHEDZZ132
Postdoctoral Research Project Funding of Shaanxi Province	2024-KF-02, 202205AR070001, 2019ZG007
Open Project of State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University	CXKJLJRC2023-07
Chuxiong Science and Technology Leading Talents
Northwest A&F University (NWAFU)

Keywords

cattle
coat color
genome assembly
high-altitude adaptation
structural variation

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Xia, X., Wang, F., Luo, X., Li, S., Lyu, Y., Zheng, Y., Ma, Z., Qu, K., Song, R., Liu, J., Zhang, J., Wangdui, B., Zhuzha, B., Quji, S., Zhao, L., Wangmu, S., Luobu, C., Cangjue, N., Luosang, D., ... Chen, N. (2025). Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle. Advanced Science, Article e03258. Advance online publication. https://doi.org/10.1002/advs.202503258

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title = "Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle",

abstract = "Structural variations (SVs) play crucial roles in the evolutionary adaptation of domesticated animals to natural and human-controlled environments, but SVs have not been explored in Tibetan cattle, which recently migrated and rapidly adapted to the high altitudes of the Qinghai-Tibetan Plateau (QTP). In this study, a de novo chromosome-level genome assembly for Tibetan cattle is constructed. It is found that using a lineage-specific reference genome significantly increased variant detection accuracy and completeness. Analysis of long-read sequencing data from 36 high-altitude QTP and 48 low-altitude cattle identified 222 528 SVs and 259 SV hotspot regions. Positively selected SVs in high-altitude cattle are related to energy metabolism erythropoiesis and angiogenesis, and peroxisomal metabolism. A 102-bp intronic deletion in GNPAT likely upregulated its expression. It is distinguished 7293 SVs that may be introgressed from yak, including variants upstream of the hypoxia-inducing gene EGLN1. Finally, a ≈2-Mb heterozygous inversion and two translocations on chromosome 6 are likely associated with the cattle gray coat via regulatory effects on the KIT gene. The results confirm the importance of SVs in evolutionary adaptation and the contribution yak-introgressed SVs to the rapid acclimatization of QTP cattle.",

keywords = "cattle, coat color, genome assembly, high-altitude adaptation, structural variation",

author = "Xiaoting Xia and Fuwen Wang and Xiaoyu Luo and Shuang Li and Yang Lyu and Yining Zheng and Zhijie Ma and Kaixing Qu and Rende Song and Jianyong Liu and Jicai Zhang and Basang Wangdui and Basang Zhuzha and Suolang Quji and Li Zhao and Silang Wangmu and Ciren Luobu and Nima Cangjue and Danzeng Luosang and Suolang Sizhu and Haijian Cheng and Ruizhe Li and Zhipeng Wu and Ruihua Dang and Yongzhen Huang and Xianyong Lan and Luohao Xu and Haifei Hu and WaiYee Low and Zhuqing Zheng and Yu Wang and Yuanpeng Gao and Lu Deng and Lenstra, {Johannes A} and Jianlin Han and Xueyi Yang and Wenfa Lyu and Bizhi Huang and Chuzhao Lei and Ningbo Chen",

note = "{\textcopyright} 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.",

year = "2025",

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doi = "10.1002/advs.202503258",

language = "English",

journal = "Advanced Science",

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Xia, X, Wang, F, Luo, X, Li, S, Lyu, Y, Zheng, Y, Ma, Z, Qu, K, Song, R, Liu, J, Zhang, J, Wangdui, B, Zhuzha, B, Quji, S, Zhao, L, Wangmu, S, Luobu, C, Cangjue, N, Luosang, D, Sizhu, S, Cheng, H, Li, R, Wu, Z, Dang, R, Huang, Y, Lan, X, Xu, L, Hu, H, Low, W, Zheng, Z, Wang, Y, Gao, Y, Deng, L, Lenstra, JA, Han, J, Yang, X, Lyu, W, Huang, B, Lei, C & Chen, N 2025, 'Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle', Advanced Science. https://doi.org/10.1002/advs.202503258

TY - JOUR

T1 - Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle

AU - Xia, Xiaoting

AU - Wang, Fuwen

AU - Luo, Xiaoyu

AU - Li, Shuang

AU - Lyu, Yang

AU - Zheng, Yining

AU - Ma, Zhijie

AU - Qu, Kaixing

AU - Song, Rende

AU - Liu, Jianyong

AU - Zhang, Jicai

AU - Wangdui, Basang

AU - Zhuzha, Basang

AU - Quji, Suolang

AU - Zhao, Li

AU - Wangmu, Silang

AU - Luobu, Ciren

AU - Cangjue, Nima

AU - Luosang, Danzeng

AU - Sizhu, Suolang

AU - Cheng, Haijian

AU - Li, Ruizhe

AU - Wu, Zhipeng

AU - Dang, Ruihua

AU - Huang, Yongzhen

AU - Lan, Xianyong

AU - Xu, Luohao

AU - Hu, Haifei

AU - Low, WaiYee

AU - Zheng, Zhuqing

AU - Wang, Yu

AU - Gao, Yuanpeng

AU - Deng, Lu

AU - Lenstra, Johannes A

AU - Han, Jianlin

AU - Yang, Xueyi

AU - Lyu, Wenfa

AU - Huang, Bizhi

AU - Lei, Chuzhao

AU - Chen, Ningbo

PY - 2025/6/5

Y1 - 2025/6/5

N2 - Structural variations (SVs) play crucial roles in the evolutionary adaptation of domesticated animals to natural and human-controlled environments, but SVs have not been explored in Tibetan cattle, which recently migrated and rapidly adapted to the high altitudes of the Qinghai-Tibetan Plateau (QTP). In this study, a de novo chromosome-level genome assembly for Tibetan cattle is constructed. It is found that using a lineage-specific reference genome significantly increased variant detection accuracy and completeness. Analysis of long-read sequencing data from 36 high-altitude QTP and 48 low-altitude cattle identified 222 528 SVs and 259 SV hotspot regions. Positively selected SVs in high-altitude cattle are related to energy metabolism erythropoiesis and angiogenesis, and peroxisomal metabolism. A 102-bp intronic deletion in GNPAT likely upregulated its expression. It is distinguished 7293 SVs that may be introgressed from yak, including variants upstream of the hypoxia-inducing gene EGLN1. Finally, a ≈2-Mb heterozygous inversion and two translocations on chromosome 6 are likely associated with the cattle gray coat via regulatory effects on the KIT gene. The results confirm the importance of SVs in evolutionary adaptation and the contribution yak-introgressed SVs to the rapid acclimatization of QTP cattle.

AB - Structural variations (SVs) play crucial roles in the evolutionary adaptation of domesticated animals to natural and human-controlled environments, but SVs have not been explored in Tibetan cattle, which recently migrated and rapidly adapted to the high altitudes of the Qinghai-Tibetan Plateau (QTP). In this study, a de novo chromosome-level genome assembly for Tibetan cattle is constructed. It is found that using a lineage-specific reference genome significantly increased variant detection accuracy and completeness. Analysis of long-read sequencing data from 36 high-altitude QTP and 48 low-altitude cattle identified 222 528 SVs and 259 SV hotspot regions. Positively selected SVs in high-altitude cattle are related to energy metabolism erythropoiesis and angiogenesis, and peroxisomal metabolism. A 102-bp intronic deletion in GNPAT likely upregulated its expression. It is distinguished 7293 SVs that may be introgressed from yak, including variants upstream of the hypoxia-inducing gene EGLN1. Finally, a ≈2-Mb heterozygous inversion and two translocations on chromosome 6 are likely associated with the cattle gray coat via regulatory effects on the KIT gene. The results confirm the importance of SVs in evolutionary adaptation and the contribution yak-introgressed SVs to the rapid acclimatization of QTP cattle.

KW - cattle

KW - coat color

KW - genome assembly

KW - high-altitude adaptation

KW - structural variation

UR - http://www.scopus.com/inward/record.url?scp=105007731966&partnerID=8YFLogxK

U2 - 10.1002/advs.202503258

DO - 10.1002/advs.202503258

M3 - Article

C2 - 40470718

SN - 2198-3844

JO - Advanced Science

JF - Advanced Science

M1 - e03258

ER -

Structural Variations Associated with Adaptation and Coat Color in Qinghai-Tibetan Plateau Cattle

Abstract

Bibliographical note

Funding

Keywords

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