Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors
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Abstract
Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with increased [corrected] microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans.
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Some archaic alleles have been shown to confer an adaptive advantage for modern humans.
“Some archaic alleles have been shown to confer an adaptive advantage for modern humans”
From Functional implications of Neandertal introgression in modern humans (2017) · cites this paper as [1]
A number of instances of adaptive introgression have been described, generally affecting systems that influence immune and metabolic phenotypes.
“a number of instances of adaptive introgression have been described, generally affecting systems that influence immune and metabolic phenotypes [1, 5, 10, 22, 40, 41].”
From Functional implications of Neandertal introgression in modern humans (2017) · cites this paper as [1]
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- Authors
- Dannemann, M., Andrés, A. M., & Kelso, J.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- Corresponding author
- Kelso, Janet
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 98
- Issue
- 1
- Pages
- 22-33
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4716682
- OpenAlex
- W2226561648
- Cited by
- 249
- References
- 61
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 19 · 2023: 17 · 2022: 22 · 2021: 30 · 2020: 27 · 2019: 30 · 2018: 24 · 2017: 23 · 2016: 29 · 2015: 2
- FWCI
- 137.50
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-02-04)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 1052, project A02)
- Max-Planck-Gesellschaft
- 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 Associations and Epidemiology
- Keywords
- adaptive introgression, Neanderthals, Denisovans, Toll-like receptors, archaic human admixture, positive selection, innate immunity, microbial resistance, allergic diseases, gene expression, allele frequency, genetic differentiation
- MeSH terms
- Adaptation, Physiological, Animals, Cell Line, Haplotypes, Humans, Polymorphism, Single Nucleotide, Toll-Like Receptors, Neanderthals
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