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.
Animal Genomics, ETH Zürich, Zürich 8092, Switzerland.
Genomics Proteomics Bioinformatics. 2024 Jul 3;22(2). doi: 10.1093/gpbjnl/qzae030.
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-Tibet 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. The haplotype A carried two homologous 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 haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed 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.
绵羊最初在新月沃地被驯化，随后传播到世界各地，在那里它们遇到了各种环境条件。藏羊在过去的 3000 年里已经适应了青藏高原的高海拔环境。为了探索与藏羊高海拔适应相关的基因组变异，我们分析了代表不同海拔高度的 60 个绵羊品种/群体的 994 个全基因组的 Illumina 短读序列、13 个品种的 PacBio 高保真（HiFi）读长和 12 个绵羊器官的 96 个转录组。我们对居住海拔与 34298967 个变体之间进行了关联测试，以研究海拔适应的遗传结构。我们利用高度准确的 HiFi 读长补充了当前的绵羊参考组装，在最显著关联的β-珠蛋白基因座，并验证了 13 个绵羊品种中存在两种单倍型 A 和 B。单倍型 A 携带两个同源基因簇：（1）HBE1、HBE2、HBB-like 和 HBBC，和（2）HBE1-like、HBE2-like、HBB-like 和 HBB；而单倍型 B 缺乏第一个基因簇。高海拔绵羊高度频繁或几乎固定携带单倍型 A，而低海拔绵羊则以单倍型 B 为主。我们进一步证明，携带单倍型 A 的绵羊血红蛋白-O2 亲和力增加，而携带单倍型 B 的绵羊则相反。另一个高度相关的基因组区域包含 EGLN1 基因，该基因在高海拔和低海拔绵羊之间表现出不同的表达。我们的研究结果提供了证据表明，有利等位基因的快速适应性进化在促进藏羊的环境适应中起着重要作用。
