Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs
文献类型: 外文期刊
作者: Lai, Dingwang 1 ; Qu, Xiaolu 1 ; Wang, Zhen 1 ; He, Sang 1 ; Li, Xingzheng 1 ; Bao, Qi 1 ; Sun, Guangming 2 ; Zhang, Jian 3 ; Zhu, Yanbin 2 ; Yi, Guoqiang 1 ;
作者机构: 1.Chinese Acad Agr Sci, State Key Lab Genome & Multi Technol, Agr Genom Inst Shenzhen,Key Lab Livestock & Poultr, Shenzhen Branch,Guangdong Lab Lingnan Modern Agr, Shenzhen 518124, Peoples R China
2.Xizang Acad Agr & Anim Husb Sci, Inst Anim Husb & Vet Med, Lhasa 850000, Peoples R China
3.Gongbogyamda Cty Anim Dis Prevent Stn, Nyingchi 860200, Peoples R China
4.Bama Yao Autonomous Cty Rural Revitalizat Res Inst, Bama 547500, Peoples R China
关键词: high-altitude adaptation; Tibetan pigs; lung tissue; multi-omics integration
期刊名称:MOLECULAR BIOLOGY AND EVOLUTION ( 影响因子:5.3; 五年影响因子:11.9 )
ISSN: 0737-4038
年卷期: 2025 年 42 卷 7 期
页码:
收录情况: SCI
摘要: The Qinghai-Tibet Plateau, characterized by its extreme environmental conditions, presents significant challenges to life, making it an ideal region for studying adaptation and evolution. Tibetan pigs, known for their high genetic diversity and exceptional adaptability to high altitudes, serve as excellent models for investigating high-altitude adaptation. While previous studies have extensively identified genetic determinants associated with high-altitude adaptation, the molecular mechanisms, particularly cis-regulatory patterns, remain poorly understood. Here, we conducted a selective sweep analysis using 484 genomes from Chinese and Western pig breeds across various altitudes, revealing 38.56 Mb of genomic regions under selection in Tibetan pigs. Enrichment analysis identified the lung as the primary functional tissue involved in high-altitude adaptation, supported by tissue-specific transcriptional and regulatory patterns observed between Tibetan and Meishan pigs (low altitude). By integrating genomic, RNA-seq, ATAC-seq, and H3K27ac HiChIP data, we constructed comprehensive enhancer-promoter regulatory maps of candidate genes and pinpointed promising genetic determinants associated with high-altitude adaptation, including SNPs in EPAS1, KLF13, SPRED1, and CFD. These loci were predicted to influence chromatin accessibility and the interactions of regulatory elements, with altered binding strength of relevant transcription factors. Further in vitro experiments confirmed that these loci function as allele-specific enhancers, modulating the expression of target genes. Our findings elucidate the regulatory basis of high-altitude adaptation in Tibetan pigs and provide valuable insights for exploring hypoxia-related diseases in livestock and humans.
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