Table_5_Population Structure, and Selection Signatures Underlying High-Altitude Adaptation Inferred From Genome-Wide Copy Number Variations in Chinese Indigenous Cattle.xls

Copy number variations (CNVs) have been demonstrated as crucial substrates for evolution, adaptation and breed formation. Chinese indigenous cattle breeds exhibit a broad geographical distribution and diverse environmental adaptability. Here, we analyzed the population structure and adaptation to high altitude of Chinese indigenous cattle based on genome-wide CNVs derived from the high-density BovineHD SNP array. We successfully detected the genome-wide CNVs of 318 individuals from 24 Chinese indigenous cattle breeds and 37 yaks as outgroups. A total of 5,818 autosomal CNV regions (683 bp–4,477,860 bp in size), covering ~14.34% of the bovine genome (UMD3.1), were identified, showing abundant CNV resources. Neighbor-joining clustering, principal component analysis (PCA), and population admixture analysis based on these CNVs support that most Chinese cattle breeds are hybrids of Bos taurus taurus (hereinafter to be referred as Bos taurus) and Bos taurus indicus (Bos indicus). The distribution patterns of the CNVs could to some extent be related to the geographical backgrounds of the habitat of the breeds, and admixture among cattle breeds from different districts. We analyzed the selective signatures of CNVs positively involved in high-altitude adaptation using pairwise Fst analysis within breeds with a strong Bos taurus background (taurine-type breeds) and within Bos taurus×Bos indicus hybrids, respectively. CNV-overlapping genes with strong selection signatures (at top 0.5% of Fst value), including LETM1 (Fst = 0.490), TXNRD2 (Fst = 0.440), and STUB1 (Fst = 0.420) within taurine-type breeds, and NOXA1 (Fst = 0.233), RUVBL1 (Fst = 0.222), and SLC4A3 (Fst=0.154) within hybrids, were potentially involved in the adaptation to hypoxia. Thus, we provide a new profile of population structure from the CNV aspects of Chinese indigenous cattle and new insights into high-altitude adaptation in cattle.

拷贝数变异（Copy number variations, CNVs）已被证实为物种演化、适应性形成以及品种形成过程中的关键遗传基础。中国本土牛品种地理分布广泛，且具备多样的环境适应性。本研究基于高密度牛HD SNP芯片（BovineHD SNP array）获取的全基因组范围CNV数据，对中国本土牛品种的群体结构及高海拔适应性展开分析。本研究成功检测了24个中国本土牛品种共计318个个体的全基因组CNV，并以37头牦牛作为外类群。最终共鉴定得到5818个常染色体CNV区域（长度范围683 bp至4477860 bp），覆盖牛参考基因组UMD3.1的约14.34%，表明中国本土牛拥有丰富的CNV遗传资源。通过上述CNV数据开展的邻接聚类分析、主成分分析（Principal Component Analysis, PCA）以及群体血统混合分析结果显示，绝大多数中国本土牛品种均为普通牛（Bos taurus taurus，下文简称普通牛）与瘤牛（Bos indicus）的杂交后代。CNV的分布模式在一定程度上与各品种的栖息地理环境以及不同区域牛品种间的血统混合情况相关。本研究分别以具有强普通牛血统背景的品种（普通牛型品种）以及普通牛×瘤牛杂交群体为研究对象，通过两两群体分化系数（Fst）分析，筛选出与高海拔适应性正相关的CNV选择信号。位于Fst值前0.5%的强选择信号CNV重叠基因，在普通牛型品种中包括LETM1（Fst=0.490）、TXNRD2（Fst=0.440）与STUB1（Fst=0.420），在杂交群体中包括NOXA1（Fst=0.233）、RUVBL1（Fst=0.222）与SLC4A3（Fst=0.154），上述基因均可能参与低氧适应性调控过程。综上，本研究从CNV维度揭示了中国本土牛的群体结构特征，并为牛类高海拔适应性研究提供了全新的见解。