ADAPTATION TO HIGH ALTITUDE IN THE CAUCASUS: TESTING THE HYPOTHESIS OF CONVERGENT EVOLUTION USING THE EGLN1 AND SPRTN GENES

BACKGROUND: Despite compelling evidence of convergent evolution in the EGLN1 and SPRTN genes in indigenous populations of the Andes and Tibet, the role of these adaptive variants in inhabitants of other high-altitude regions, particularly the Caucasus, remains unexplored. This study will determine whether the identified genetic pattern is universal or whether Caucasian populations exhibit unique pathways of genetic adaptation to high altitudes.

AIM: To identify differences in the distribution of allele and genotype frequencies of genetic variants rs479200 of the EGLN1 gene and rs2437150 of the SPRTN gene between the highland population of Balkars and the population of Kabardians inhabiting the plains and foothills of the Central Caucasus to assess the contribution of these variants to the formation of adaptive traits to hypoxia.

METHODS: Samples of Balkars (N=132) and Kabardins (N=131) were formed from representatives of these ethnic groups living in the highland and lowland zones of the Kabardino-Balkarian Republic, respectively. For genotyping, the technology for determining single nucleotide polymorphisms using the KASP method was used.

RESULTS: Population genetic analysis revealed significant differences in the distribution of genotypes and alleles of the EGLN1 and SPRTN hypoxia genes between Balkars and Kabardians. In the Balkar population, signs of selection were detected, including increased heterozygosity for the rs479200 locus of the EGLN1 gene and a higher frequency of the adaptive allele rs2437150 of the SPRTN gene. These differences likely reflect local adaptation to high-altitude conditions, despite the overall genetic similarity of the Caucasus populations.

CONCLUSION: A study of the role of the EGLN1 and SPRTN genes in the Balkars' adaptation to high altitude revealed a complex picture: the EGLN1 gene exhibits a unique, balanced selection favoring heterozygotes, while the SPRTN gene exhibits universal, positive selection. This demonstrates a combination of unique and universal evolutionary pathways for adaptation to hypobaric hypoxia.