ArticleAmerican journal of human genetics2016
Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 259 citations in OpenAlex.
- Ancient DNA and Human Physiology.Physiology (Bethesda, Md.) · 2026Review
- A Genetic Risk Variant Associated With the Risk of Primary Biliary Cholangitis Is Inherited From Neanderthals.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Genomic insights into natural selection in recent human history.Nature reviews. Genetics · 2026Review
- Ancient DNA as a temporal lens: reconstructing evolution, migration, and disease dynamics.Journal, genetic engineering & biotechnology · 2026Review
- Article
- Fast pairwise coalescence enables gene-resolution scans for recent selection in diverse human populations.bioRxiv : the preprint server for biology · 2026Article
- Insights into human adaptation from ancient DNA.Nature genetics · 2026Review
- Insights into infectious diseases through ancient pathogen genomics.Nature reviews. Microbiology · 2026Review
- Mapping the gene regulatory landscape of archaic hominin introgression in modern Papuans.PLoS genetics · 2026Article
- Recent advances in methods to characterize archaic introgression in modern humans.Genome research · 2026Review
- Association of Chromosome 3p21.32 Haplotype Blocks Introgressed from Neanderthals with Critical COVID-19 in a Spanish Cohort.Life (Basel, Switzerland) · 2025Article
- Archaic adaptive introgression in modern human reproductive genes.Communications biology · 2025Article
- Reconstructing the 3D genome organization of Neanderthals reveals that chromatin folding shaped phenotypic and sequence divergence.bioRxiv : the preprint server for biology · 2025Article
- Molecular characterization of the archaic HLA-B∗73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2.The Journal of biological chemistry · 2025Article
- Replicate geographic transects across a hybrid zone reveal parallelism and differences in the genetic architecture of reproductive isolation.Evolution letters · 2025Article
- Genome-Wide Demographic Analyses of Balaenid Whales Revealed Complex History of Gene Flow Associated with Past Climate Oscillation.Genome biology and evolution · 2025Article
- Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds.Veterinary medicine and science · 2025Article
- Archaic hominin admixture and its consequences for modern humans.Current opinion in genetics & development · 2025Review
- Adaptive introgression in modern human circadian rhythm genes.Npj biological timing and sleep · 2025Article
- Neanderthal ancestry through time: Insights from genomes of ancient and present-day humans.Science (New York, N.Y.) · 2024Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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