Selection Signatures Analysis Reveals Genes Associated with High-Altitude Adaptation in Tibetan Goats from Nagqu, Tibet

Simple Summary In the process of domestication, goats have undergone long-term artificial and natural selection, leading to differences among goat breeds and leaving different selection traces on the genome. However, the genetic components underlying high-altitude adaptation remain largely unknown. Here, we genotyped four goat breeds using the Illumina Caprine 50K single nucleotide polymorphism (SNP) Chip. One highland breed (Tibetan goat) compared with three lowland breeds (Huanghuai goat, Taihang goat and Xinjiang goat) to identify the molecular basis of high-altitude adaptation. So, we investigated selection signatures using thedistatistic of four goat breeds and some genes in Tibetan goats related to high-altitude adaptation were identified. In addition, q-PCR validated the gene expression level in Tibetan goats and Huanghuai goats. This information may be valuable for the study of the genetic uniqueness of Tibetan goats and increased understanding of the hypoxic adaptation mechanism of Tibetan goats on the plateau. Tibetan goat is an ancient breed, which inhabits the adverse conditions of the plateaus in China. To investigate the role of selection in shaping its genomes, we genotyped Tibetan goats (Nagqu Prefecture, above 4500 m) and three lowland populations (Xinjiang goats, Taihang goats and Huanghuai goats). The result of PCA, neighbor-joining (N-J) tree and model-based clustering showed that the genetic structure between the Tibetan goat and the three lowland populations has significant difference. As demonstrated by thedistatistic, we found that some genes were related to the high-altitude adaptation of Tibetan goats. Functional analysis revealed that these genes were enriched in the VEGF (vascular endothelial growth factor) signaling pathway and melanoma, suggesting that nine genes (FGF2,EGFR,AKT1,PTEN,MITF,ENPEP,SIRT6,KDR, andCDC42) might have important roles in the high-altitude adaptation of Nagqu Tibetan goats. We also found that theLEPRgene was under the strongest selection (divalue = 16.70), and it could induce upregulation of the hypoxic ventilatory response. In addition, five genes (LEPR,LDB1,EGFR,NOX4andFGF2) with highdivalues were analyzed using q-PCR. Among them, we found thatLEPR,LDB1andFGF2exhibited higher expression in the lungs of the Tibetan goats;LEPR,EGFRandLDB1exhibited higher expression in the hearts of the Huanghuai goat. Our results suggest thatLEPR,LDB1,EGFRandFGF2genes may be related to the high-altitude adaptation of the goats. These findings improve our understanding of the selection of the high-altitude adaptability of the Nagqu Tibetan goats and provide new theoretical knowledge for the conservation and utilization of germplasm resources.