The oligoadenylate synthetase (OAS) locus on chromosome 12, which harbours three genes (OAS1, OAS2, OAS3) encoding the 2’-5’ OAS enzymes has received considerable attention due to its clear signatures in multiple archaic haplotypes in populations outside of Africa and the critical role OAS genes play in the innate immune response to viruses.
Researchers first identified an introgressed haplotype of OAS1 from Denisovans that is restricted to individuals in Indonesia and Melanesia. Later, a Neandertal haplotype at the OAS locus that spans a ~190 kb region between two surrounding recombination hotspots was identified.
The Neandertal-derived alleles were found in an elevated frequency in the OAS locus relative to average levels of Neandertal ancestry in Europeans. OAS genes play a key role in protective immunity against viral infections. This finding raises the possibility that introgressed Neandertal haplotypes at OAS may have been adaptive in modern humans. Some studies provide suggestive evidence of adaptive introgression at the OAS locus.
A survey of DNA sequence variation in the OAS gene cluster on chromosome 12 provides strong evidence that a haplotype extending for ~185 kb introgressed from Neandertals. This haplotype is nearly restricted to Eurasians and is estimated to have diverged from the Neandertal sequence ~125 kya.
The human reference sequence for OAS1 is very similar to that of Neandertals.
This haplotype is significantly associated with functional consequences at the level of transcriptional regulation of innate immune responses. The Neandertal-introgressed haplotype likely reintroduced an ancestral splice variant of OAS1 encoding a more active protein, suggest studies.
This is the second locus in the human genome, after STAT2, carrying distinct haplotypes that appear to have introgressed separately from both Neandertals and Denisova, says a study Neandertal Origin of Genetic Variation at the Cluster of OAS Immunity Genes, appeared in Molecular Biology and Evolution.
Strong evidence, however, of positive selection in the OAS region is still lacking.