The shaping of modern human immune systems by multiregional admixture with archaic humans
Open accessAbstract
Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.
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- Authors
- Abi-Rached, L., Jobin, M. J., Kulkarni, S., McWhinnie, A., Dalva, K., Gragert, L., Babrzadeh, F., Gharizadeh, B., Luo, M., Plummer, F. A., Kimani, J., Carrington, M., Middleton, D., Rajalingam, R., Beksac, M., Marsh, S. G. E., Maiers, M., Guethlein, L. A., Tavoularis, S., Little, A.-M., Green, R. E., Norman, P. J., & Parham, P.
- Affiliations
- Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
- Santa Clara University (US)
- Stanford Medicine (US)
- Anthony Nolan (GB)
- Ankara University (TR)
- National Marrow Donor Program (US)
- Public Health Agency of Canada (CA)
- University of Nairobi (KE)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of Liverpool (GB)
- University of California, Los Angeles (US)
- Department of Hematology, Ankara University, 06520 Ankara, Turkey.
- Canadian Blood Services (CA)
- University of California, Santa Cruz (US)
- Corresponding author
- Parham, Peter
- ORCID
- Venue
- Science
- Published
- 2011-10-07
- Volume
- 334
- Issue
- 6052
- Pages
- 89-94
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3677943
- OpenAlex
- W2142215232
- Cited by
- 537
- References
- 34
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 20 · 2023: 28 · 2022: 61 · 2021: 28 · 2020: 28 · 2019: 35 · 2018: 32 · 2017: 44 · 2016: 45 · 2015: 41 · 2014: 49 · 2013: 52 · 2012: 40
- FWCI
- 206.45
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E))
- National Institute of Allergy and Infectious Diseases (AI 031168, R01AI031168)
- National Center for Research Resources (RR000165, P51RR000165)
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- HLA class I, Denisovans, Neanderthals, archaic human admixture, introgression, human leukocyte antigen, NK cell receptors, balancing selection, immune system evolution, Eurasian populations, African admixture
- MeSH terms
- Adaptation, Biological, Alleles, Animals, Genes, MHC Class I, Haplotypes, Humans, Hybridization, Genetic, Killer Cells, Natural, Ligands, Molecular Sequence Data, Selection, Genetic, Genetic Variation, Hominidae, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, Linkage Disequilibrium, Evolution, Molecular, Black People, White People, Asian People, Native Hawaiian or Pacific Islander, Racial Groups, Receptors, KIR
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