Search for genetic variations that allow populations to thrive in high-altitude environment of Caucasus highlands

High-altitude hypoxia refers to the state of reduced oxygen availability experienced at high elevations, which poses significant physiological challenges. Genetic adaptations to this condition involve mutations in various genes that regulate oxygen sensing, erythropoiesis, and metabolic processes, enabling populations indigenous to high-altitude regions to maintain adequate tissue oxygenation and metabolic function under chronic hypoxic conditions. The aim of the study was to investigate the 1q42.2 region in Caucasian populations to identify alleles that may contribute to evolutionary adaptation. We studied a ~ 700 kb region within the 1q42.2 locus in Caucasus populations using the integrated selection of alleles favored by evolution (iSAFE) method. The study included 308 individuals from five ethnic groups inhabiting the high-altitude regions of the North Caucasus (Balkars, Ingush, Karachays, and Chechens) and the South Caucasus (Armenians). Whole-genome sequencing of the samples was performed on the DNBSEQ-T7 platform. The genomic region chr1:231046413–231737003 (GRCh38.p14) was selected due to its established role in high-altitude adaptation across various global populations. Analysis revealed a region encompassing five variants in the SPRTN and EGLN1 genes with the highest iSAFE scores in Balkar samples. Similarly, five high-scoring genetic variants were identified in the Karachay population within the same locus. In contrast, only one variant in the EGLN1 gene showed a maximum score in both the Ingush and Armenian groups. The study found evidence of positive selection for two SPRTN gene variants, confirmed across all studied populations except Chechens.