Positive selection in the genomes of two Papua New Guinean populations at distinct altitude levels

Abstract

Highlanders and lowlanders of Papua New Guinea have faced distinct environmental stress, such as hypoxia and environment-specific pathogen exposure, respectively. In this study, we explored the top genomics regions and the candidate driver SNPs for selection in these two populations using newly sequenced whole-genomes of 54 highlanders and 74 lowlanders. We identified two candidate SNPs under selection - one in highlanders, associated with red blood cell traits and another in lowlanders, which is associated with white blood cell count – both potentially influencing the heart rate of Papua New Guineans in opposite directions. We also observed four candidate driver SNPs that exhibit linkage disequilibrium with an introgressed haplotype, highlighting the need to explore the possibility of adaptive introgression within these populations. This study reveals that the signatures of positive selection in highlanders and lowlanders of Papua New Guinea align closely with the challenges they face, which are specific to their environments.

Denisovan admixture facilitated environmental adaptation in Papua New Guinean populations

“…Furthermore, genetic variants exhibiting signatures of selection in the PNG highlanders under investigation have been associated with variations in red blood cell composition and cardiovascular phenotypes. This observation aligns with findings in other high-altitude populations ( 6 ). To investigate whether similar phenotypes are influenced by archaic introgression, we examined the gene content of highly differentiated archaic haplotypes and the phenotypic associations of aSNPs linked to them.…”

“…These findings imply that Denisovan DNA played a significant role in adaptive processes for these populations. Highly differentiated haplotypes that exhibited higher frequencies in highlanders overlapped several genes associated with early brain development, a result also observed for some of the most highly differentiated nonarchaic haplotypes in these populations ( 6 ). This result might reflect adaptive patterns to highlander-specific environmental factors.…”

“…Notably, among the Denisovan-like set 2 haplotypes associated with genes in these categories was a haplotype encompassing four members of the Guanylate-binding proteins family [ GBP1 , GBP2 , GBP4 , and GBP7 (Guanylate-Binding Protein 7)]—proteins crucial in immune response mechanisms ( 41 ). This specific haplotype had been previously identified in Melanesians as a candidate for positive selection ( 6 , 27 ) and carries an archaic variant introducing a missense variant to GBP7 ( Fig. 3 B and SI Appendix ).…”

“…In this study, our objective was to evaluate the degree to which DNA inherited from past interbreeding with archaic humans has contributed to shaping local adaptation of two geographically distinct PNG populations, each confronting unique environmental challenges. To address this task, we characterized the genomic landscape of Neandertal and Denisovan DNA in the genomes of 74 PNG individuals residing in the lowlands of Daru Island and 54 individuals inhabiting the highlands of Mount Wilhelm ( Dataset S1 and Methods ) ( 6 ). The habitats of both populations are marked by notable environmental differences, primarily in terms of altitude.…”

“…These environmental challenges, such as exposure to high altitudes or region-specific pathogens, have been demonstrated to correlate with phenotypic variations among PNG populations inhabiting distinct environments ( 5 ). These challenges have also been established as factors contributing to the emergence of local genetic adaptation signatures ( 6 , 7 ). Moreover, PNG, like their counterparts in near and remote Oceania, bear a significant share of approximately 3 to 4% Denisovan DNA, ranking among the highest proportions globally ( 8 , 9 ).…”