Selection scan reveals three new loci related to high altitude adaptation in Native Andeans

Abstract

The Andean Altiplano has been occupied continuously since the late Pleistocene, ~12,000 years ago, which places the Andean natives as one of the most ancient populations living at high altitudes. In the present study, we analyzed genomic data from Native Americans living a long-time at Andean high altitude and at Amazonia and Mesoamerica lowland areas. We have identified three new candidate genes - SP100, DUOX2 and CLC - with evidence of positive selection for altitude adaptation in Andeans. These genes are involved in the TP53 pathway and are related to physiological routes important for high-altitude hypoxia response, such as those linked to increased angiogenesis, skeletal muscle adaptations, and immune functions at the fetus-maternal interface. Our results, combined with other studies, showed that Andeans have adapted to the Altiplano in different ways and using distinct molecular strategies as compared to those of other natives living at high altitudes.

Figure 1

Average PBS values in windows of 20 SNPs, using a step size of 5 SNPs. The 99.5th and 99.9th percentiles of the empirical distribution are shown as black dashed horizontal lines. Names of genes associated with the highest peaks are shown.

Figure 2

Distribution of 10,000 simulated PBS values under three neutral coalescent models. (a) Constant population model. (b) Population bottleneck model; and (c) Population bottleneck followed by expansion model. The dashed line represents the top observed PBS SNP values in the empirical datasets.

Figure 3

(a) rs13411586_C (SP100). (b) rs269866_G (DUOX2) and (c) rs440191_A (CLC) allele frequency distributions according to altitude. Populations (n ≥ 3): 1. Aymara, 2. Guahibo, 3. Guarani, 4. Kaqchikel, 5. Karitiana, 6. Kogi, 7. Maya, 8. Mixe, 9. Mixtec, 10. Piapoco, 11. Quechua, 12. Surui,13. Tepehuano, 14. Ticuna, 15. Toba, 16. Wayuu, 17. Wichi, 18. Yaghan and 19. Zapotec.