Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations
Open accessAbstract
Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ∼90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.
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The OAS locus has been repeatedly found to harbour signals of both Neanderthal and Denisovan adaptive introgression, with archaic alleles predicted to alter gene regulation.
“The OAS locus has been repeatedly found to harbour signals of both Neanderthal and Denisovan adaptive introgression, with archaic alleles predicted to alter gene regulation [52, 56].”
From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [56]
The Introduction (page unavailable) identifies a Melanesian OAS1 haplotype sharing variants with Denisova and interprets it as consistent with archaic introgression. But the Evidence for Archaic Introgression section says its preliminary Neandertal comparison resembles the human reference sequence; the paper does not establish Neandertal introgression at OAS1 or repeated findings of adaptive introgression. Functional Variation (page unavailable) predicts effects on protein sequence, not gene regulation. (LLM, conf=0.89)
Experimental — accuracy not yet measuredAt least two previous studies have shown the presence of both Neanderthal and Denisovan archaic haplotypes segregating at the OAS locus respectively within European and Papuan individuals.
“At least two previous studies have shown the presence of both Neanderthal and Denisovan archaic haplotypes segregating at this locus respectively within European [52] and Papuan [56] individuals.”
From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [56]
TNFAIP3, OAS2 and OAS3 have been repeatedly identified as harbouring archaic hominin contribution that impact immune responses to pathogens.
“all of which have been repeatedly identified as harbouring archaic hominin contribution that impact immune responses to pathogens [51, 52, 56].”
From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [56]
The Introduction identifies archaic introgression at OAS1 and describes OAS1’s antiviral role, but it does not address the claim about TNFAIP3, OAS2, or OAS3. Searches for those three genes found no passage in our copy that evaluates their archaic contribution or its effect on pathogen responses. (LLM, conf=0.76)
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“Furthermore, at least two previous studies have shown the presence of both Neandertal and Denisovan archaic haplotypes segregating at this locus respectively within European [39] and Papuan [40] individuals.”
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- Authors
- Mendez, F. L., Watkins, J. C., & Hammer, M. F.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Hammer, M. F.
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-01-16
- Volume
- 29
- Issue
- 6
- Pages
- 1513-1520
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2144162338
- Cited by
- 79
- References
- 30
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 12 · 2013: 7 · 2012: 5
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0423670)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- OAS1, archaic admixture, Denisovans, Melanesian population, innate immunity genes, haplotype diversity, nucleotide diversity, linkage disequilibrium, human evolution
- MeSH terms
- Pacific Island People, Animals, Chromosomes, Human, Pair 12, Haplotypes, Humans, Hybridization, Genetic, Melanesia, Models, Genetic, Polymorphism, Genetic, 2',5'-Oligoadenylate Synthetase, Hominidae, Linkage Disequilibrium, Sequence Analysis, DNA, 5' Untranslated Regions, Black People, Asian People, Genetic Speciation, Genotyping Techniques
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