Long-term isolation and archaic introgression shape functional genetic variation in Near Oceania.

Abstract

Near Oceanic populations harbor substantial cultural, phenotypic, and genetic diversity yet are drastically underrepresented in human genomics. We generated 177 high-coverage Near Oceanian whole genomes and analyzed them alongside 1284 worldwide genomes, revealing major distinctions among and within islands, including long-term isolation and strong population bottlenecks. We reconstructed 1.897 billion base pairs of the archaic genome, including 831.9 million base pairs of Denisovan sequence, and found evidence for introgression from three Denisovan-like groups in Near Oceanians and adaptive Denisovan introgression at <i>TRPS1</i>, a skeletal development gene also under selection in central African rainforest hunter-gatherers and highland Ecuadorians. We then performed a massively parallel reporter assay and discovered 3127 high-frequency introgressed expression-modulating variants, finding an enrichment of functional impacts on genes in the interferon-γ signaling pathway including <i>JAK1</i>, <i>GBP2</i>, and <i>OAS1</i>.