Variations in HBA gene contribute to high-altitude hypoxia adaptation via affected O transfer in Tibetan sheep.

Tibetan sheep are indigenous to the Qinghai-Xizang Plateau. Owing to the harsh hypoxic environment in this plateau, the hemoglobin (Hb) protein in Tibetan sheep has undergone adaptive changes over time. Hb is primarily responsible for transporting O and CO between the lungs and other tissues of the body. The α subunit of Hb, encoded by the HBA gene, is a crucial component of the protein. However, whether variations in the HBA gene sequence affect the adaptation of Tibetan sheep to high-altitude hypoxia remains unclear. In this study, we sequenced the HBA gene and identified three single nucleotide polymorphisms (SNPs). These SNPs were genotyped in Tibetan and Hu sheep using Kompetitive Allele-Specific PCR (KASP). The results showed that the frequencies of the AT genotype and H1H2 haplotype were higher in Tibetan sheep than in Hu sheep. Individuals with the AT genotype exhibited higher P levels, whereas those with the H1H2 haplotype exhibited lower PO and SaO levels. The higher P levels indicated that O was more readily released from oxygenated Hb into the tissues, with the lower PO and SaO levels facilitating this process. These findings indicate that variations in the HBA gene sequence contribute to enhancing O transfer efficiency in Tibetan sheep.