Homo sapiens admixed with multiple archaic hominins outside Africa (1). In particular, the Indigenous Peoples of Papua New Guinea (PNG) owe up to 5% of their genome to Denisovans, a hominin group first described in 2010 on the basis of fossil remains found in a cave in Siberia (2). However, it remains unclear what the evolutionary contribution of these archaic single nucleotide polymorphisms (aSNPs) is, with multiple recent studies pointing to non-coding aSNPs as possible sources of phenotypic variation and adaptive introgression (1,3). By integrating a recently published dataset of both Denisovan and Neandertal archaic variants segregating in populations living within PNG (4) with data from functional genomics consortia (5,6), we have investigated the contribution of aSNPs relative to variation arisen following the out of Africa dispersal across multiple genomic elements (7).
We observe an overall excess of aSNPs within active chromatin states, as well as significant differences between classes of aSNPs enriched across different cell lines, thus suggesting a scenario of archaic populations-specific contributions. Moreover, we find that high-frequency aSNPs of Denisovan origin, strongly impact immune-cell specific transcription factor binding sites, whose target genes were associated with critical immune-related processes, potentially representing instances of adaptive introgression.