Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea

Gonzalez-Buenfil, Ram, Vieyra-Sanchez, Sofia, Quinto-Cortes, Consuelo D, Oppenheimer, Stephen J, Pomat, William, Laman, Moses, Cervantes-Hernandez, Mayte C, Barberena-Jonas, Carmina, Auckland, Kathryn, Allen, Angie, Allen, Stephen ORCID: https://orcid.org/0000-0001-6675-249X, Phipps, Maude E, Huerta-Sanchez, Emilia, Ioannidis, Alexander G, Mentzer, Alexander J and Moreno-Estrada, Andres (2024) 'Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea'. Genome Biology and Evolution, Vol 16, Issue 8, evae161.

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Abstract

Papua New Guinea (PNG) hosts distinct environments mainly represented by the ecoregions of the Highlands and Lowlands that display increased altitude and a predominance of pathogens, respectively. Since its initial peopling approximately 50,000 years ago, inhabitants of these ecoregions might have differentially adapted to the environmental pressures exerted by each of them. However, the genetic basis of adaptation in populations from these areas remains understudied. Here, we investigated signals of positive selection in 62 highlanders and 43 lowlanders across 14 locations in the main island of PNG using whole-genome genotype data from the Oceanian Genome Variation Project (OGVP) and searched for signals of positive selection through population differentiation and haplotype-based selection scans. Additionally, we performed archaic ancestry estimation to detect selection signals in highlanders within introgressed regions of the genome. Among highland populations we identified candidate genes representing known biomarkers for mountain sickness (SAA4, SAA1, PRDX1, LDHA) as well as candidate genes of the Notch signaling pathway (PSEN1, NUMB, RBPJ, MAML3), a novel proposed pathway for high altitude adaptation in multiple organisms. We also identified candidate genes involved in oxidative stress, inflammation, and angiogenesis, processes inducible by hypoxia, as well as in components of the eye lens and the immune response. In contrast, candidate genes in the lowlands are mainly related to the immune response (HLA-DQB1, HLA-DQA2, TAAR6, TAAR9, TAAR8, RNASE4, RNASE6, ANG). Moreover, we find two candidate regions to be also enriched with archaic introgressed segments, suggesting that archaic admixture has played a role in the local adaptation of PNG populations.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QU Biochemistry > Genetics > QU 470 Genetic structures QU Biochemistry > Genetics > QU 500 Genetic phenomena
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/gbe/evae161
Depositing User:	Jane Rawlinson
Date Deposited:	04 Sep 2024 13:47
Last Modified:	04 Sep 2024 13:47
URI:	https://archive.lstmed.ac.uk/id/eprint/25109

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