Variations in HBA gene contribute to high-altitude hypoxia adaptation via affected O2 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 O₂ and CO₂ 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 P₅₀ levels, whereas those with the H1H2 haplotype exhibited lower PO₂ and SaO₂ levels. The higher P₅₀ levels indicated that O₂ was more readily released from oxygenated Hb into the tissues, with the lower PO₂ and SaO₂ levels facilitating this process. These findings indicate that variations in the HBA gene sequence contribute to enhancing O₂ transfer efficiency in Tibetan sheep.