Phenotype Adaptation and Positive Selection to Altitude in Papua New Guinean Highlanders

Mathilde André 1, Nicolas Brucato2, Georgi Hudjashov1, Vasili Pankratov1, Rita Kreevan1, Jason Kariwiga3,4, John Muke5, Anne Boland6, Jean-François Deleuze6, Murray P. Cox7, Matthew Leavesley3,8, Mayukh Mondal1, François-Xavier Ricaut2

1Institute of Genomics, University of Tartu, Estonia

2Laboratoire Évolution et Diversité Biologique (EDB UMR 5174), Université de Toulouse Midi-Pyrénées, France

3Strand of Anthropology, Sociology & Archaeology, School of Humanities & Social Sciences, University of Papua New Guinea, Papua New Guinea

4School of Social Science, University of Queensland, Australia

5Social Research Institute Ltd, Port Moresby, Papua New Guinea

6Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, France

7Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North, New Zealand

8ARC Centre of Excellence for Australian Biodiversity and Heritage, College of Arts, Society and Education, James Cook University, Australia

The Papua New Guinean Highlands has been continuously inhabited for 20,000 years. Since initial settlement at altitude, these populations have been exposed to low oxygen availability, which potentially resulted in stress exposure. In this project we measured phenotypes related to altitude in 70 Papuan participants living at high altitude (2300–2700 m above sea level (a.s.l).) and 86 Papuan participants living at low altitude (<100 m a.s.l.). Papuan New Guinean highlanders significantly differed in height, waist circumference, pulmonary capacity, chest depth and haemoglobin concentration. To detect if these phenotypic differences resulted from genetic selection, we looked for signatures of positive selection in 54 newly sequenced Papua New Guinean highlander genomes. We identified 21 independent genomic regions under selection. These genomic regions include genes associated with haematological traits, brain development, pregnancy success, and metabolism. Because a variant introgressed from Denisova might have aided Tibetans inhabit high altitude environments and Papuans carry a considerable introgression rate from the same archaic human, we explored the possibility of adaptative archaic introgression in the regions under selection. Finally, we defined the most likely genetic variant to drive selection in each genomic region under selection and explored which phenotypes are controlled by these variants. This study concludes that the genomes of Papua New Guinean highlanders carry unique signs of selection that allow them to live at altitude successfully.