Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans
Open accessAbstract
Neanderthals and modern humans interbred at least twice in the past 100,000 years. While there is evidence that most introgressed DNA segments from Neanderthals to modern humans were removed by purifying selection, less is known about the adaptive nature of introgressed sequences that were retained. We hypothesized that interbreeding between Neanderthals and modern humans led to (1) the exposure of each species to novel viruses and (2) the exchange of adaptive alleles that provided resistance against these viruses. Here, we find that long, frequent-and more likely adaptive-segments of Neanderthal ancestry in modern humans are enriched for proteins that interact with viruses (VIPs). We found that VIPs that interact specifically with RNA viruses were more likely to belong to introgressed segments in modern Europeans. Our results show that retained segments of Neanderthal ancestry can be used to detect ancient epidemics.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
Tajima, F. (1989) · Genetics · doi:10.1093/genetics/123.3.585 · Cited by 13,991 · see citing works
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062 · see citing works
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 4,408 · cited 2× · see citing works
“, 2016), regulatory sequences (ENCODE Project Consortium, 2012) and conserved genomic segments defined by PhastCons (Siepel et al., 2005); (2) are more highly expressed (GTEx Consortium, 2015); and (3) have more interacting protein partners in the network of human protein–protein interactions than non-VIPs (Table S2)…”
A draft sequence of the Neandertal genome
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., et al. (2010) · Science · doi:10.1126/science.1188021 · Cited by 4,318 · see citing works
The complete genome sequence of a Neanderthal from the Altai Mountains
Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P. H., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature12886 · Cited by 2,254 · see citing works
Expansion of the Gene Ontology knowledgebase and resources
The Gene Ontology Consortium (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1108 · Cited by 1,850 · see citing works
Yates, A. D., Akanni, W. A., Amode, M. R., Barrell, D. G., Billis, K., Carvalho‐Silva, D., Cummins, C. A., Clapham, P., Fitzgerald, S. F., Gil, L., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1157 · Cited by 1,246 · see citing works
The genomic landscape of Neanderthal ancestry in present-day humans
Sankararaman, S., Mallick, S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N., & Reich, D. (2014) · Nature · doi:10.1038/nature12961 · Cited by 1,107 · see citing works
The BioGRID Interaction Database: 2011 update
Stark, C., Breitkreutz, B., Chatr‐aryamontri, A., Boucher, L., Oughtred, R., Livstone, M. S., Nixon, J., Auken, K. M. V., Wang, X., Shi, X., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1116 · Cited by 853 · see citing works
An early modern human from Romania with a recent Neanderthal ancestor
Fu, Q., Hajdinjak, M., Moldovan, O. T., Constantin, S., Mallick, S., Skoglund, P., Patterson, N., Rohland, N., Lazaridis, I., Nickel, B., et al. (2015) · Nature · doi:10.1038/nature14558 · Cited by 802 · see citing works
Fine-scale recombination rate differences between sexes, populations and individuals
Kong, A., Þorleifsson, G., Gudbjartsson, D. F., Másson, G., Sigurðsson, Á., Jónasdóttir, Á., Walters, G. B., Jónasdóttir, A., Gylfason, A., Kristinsson, K. T., et al. (2010) · Nature · doi:10.1038/nature09525 · Cited by 582 · see citing works
Ancient gene flow from early modern humans into Eastern Neanderthals
Kuhlwilm, M., Gronau, I., Hubisz, M. J., de Filippo, C., Prado-Martinez, J., Kircher, M., Fu, Q., Burbano, H. A., Lalueza-Fox, C., de la Rasilla, M., et al. (2016) · Nature · doi:10.1038/nature16544 · Cited by 577 · see citing works
Resurrecting Surviving Neandertal Lineages from Modern Human Genomes
Vernot, B., & Akey, J. M. (2014) · Science · doi:10.1126/science.1245938 · Cited by 562 · see citing works
The shaping of modern human immune systems by multiregional admixture with archaic humans
Abi-Rached, L., Jobin, M. J., Kulkarni, S., McWhinnie, A., Dalva, K., Gragert, L., Babrzadeh, F., Gharizadeh, B., Luo, M., Plummer, F. A., et al. (2011) · Science · doi:10.1126/science.1209202 · Cited by 537 · see citing works
Evidence for archaic adaptive introgression in humans
Racimo, F., Sankararaman, S., Nielsen, R., & Huerta-Sánchez, E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3936 · Cited by 521 · see citing works
Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
Nédélec, Y., Sanz, J., Baharian, G., Szpiech, Z. A., Pacis, A., Dumaine, A., Grenier, J.-C., Freiman, A., Sams, A. J., Hebert, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.025 · Cited by 512 · see citing works
Genetic adaptation and Neandertal admixture shaped the immune system of human populations
Quach, H., Rotival, M., Pothlichet, J., Loh, Y.-H. E., Dannemann, M., Zidane, N., Laval, G., Patin, E., Harmant, C., Lopez, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.024 · Cited by 475 · see citing works
The Date of Interbreeding between Neandertals and Modern Humans
Sankararaman, S., Patterson, N., Li, H., Pääbo, S., & Reich, D. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002947 · Cited by 460 · see citing works
Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals
Vernot, B., Tucci, S., Kelso, J., Schraiber, J. G., Wolf, A. B., Gittelman, R. M., Dannemann, M., Grote, S., McCoy, R. C., Norton, H., et al. (2016) · Science · doi:10.1126/science.aad9416 · Cited by 459 · see citing works
Widespread Genomic Signatures of Natural Selection in Hominid Evolution
McVicker, G., Gordon, D., Davis, C., & Green, P. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000471 · Cited by 456 · see citing works
The Genetic Cost of Neanderthal Introgression
Harris, K., & Nielsen, R. (2016) · Genetics · doi:10.1534/genetics.116.186890 · Cited by 419 · see citing works
Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics
Khurana, E., Fu, Y., Colonna, V., Mu, X. J., Kang, H. M., Lappalainen, T., Sboner, A., Lochovsky, L., Chen, J., Harmanci, A. O., et al. (2013) · Science · doi:10.1126/science.1235587 · Cited by 359 · see citing works
Viruses are a dominant driver of protein adaptation in mammals
Enard, D., Cai, L., Gwennap, C., & Petrov, D. A. (2016) · eLife · doi:10.7554/elife.12469 · Cited by 353 · see citing works
Self-citationSpillover and pandemic properties of zoonotic viruses with high host plasticity
Kreuder Johnson, C., Hitchens, P. L., Smiley Evans, T., Goldstein, T., Thomas, K., Clements, A., Joly, D. O., Wolfe, N. D., Daszak, P., Karesh, W. B., et al. (2015) · Scientific Reports · doi:10.1038/srep14830 · Cited by 353 · see citing works
The Impact of Recombination on Nucleotide Substitutions in the Human Genome
Duret, L., & Arndt, P. F. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000071 · Cited by 347 · see citing works
FunSeq2: A framework for prioritizing noncoding regulatory variants in cancer
Fu, Y., Liu, Z., Lou, S., Bedford, J., Mu, X. J., Yip, K. Y.-L., Khurana, E., & Gerstein, M. (2014) · Genome biology · doi:10.1186/s13059-014-0480-5 · Cited by 334 · see citing works
The landscape of recombination in African Americans
Hinch, A. G., Tandon, A., Patterson, N. J., Song, Y., Rohland, N., Palmer, C. D., Chen, G. K., Wang, K., Buxbaum, S. G., Akylbekova, E. L., et al. (2011) · Nature · doi:10.1038/nature10336 · Cited by 311 · see citing works
The Strength of Selection against Neanderthal Introgression
Juric, I., Aeschbacher, S., & Coop, G. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1006340 · Cited by 309 · see citing works
Geoghegan, J. L., Duchêne, S., & Holmes, E. C. (2017) · PLOS Pathogens · doi:10.1371/journal.ppat.1006215 · Cited by 275 · see citing works
Deschamps, M., Laval, G., Fagny, M., Itan, Y., Abel, L., Casanova, J.-L., Patin, E., & Quintana-Murci, L. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.014 · Cited by 257 · see citing works
Dannemann, M., Andrés, A. M., & Kelso, J. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.015 · Cited by 249 · see citing works
VirHostNet 2.0: surfing on the web of virus/host molecular interactions data
Guirimand, T., Delmotte, S., & Navratil, V. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1121 · Cited by 237 · see citing works
Signatures of Archaic Adaptive Introgression in Present-Day Human Populations
Racimo, F., Marnetto, D., & Huerta-Sánchez, E. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw216 · Cited by 200 · see citing works
Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments
Gittelman, R. M., Schraiber, J. G., Vernot, B., Mikacenic, C., Wurfel, M. M., & Akey, J. M. (2016) · Current Biology · doi:10.1016/j.cub.2016.10.041 · Cited by 181 · see citing works
Mendez, F. L., Watkins, J. C., & Hammer, M. F. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.06.015 · Cited by 156 · see citing works
Complex History of Admixture between Modern Humans and Neandertals
Vernot, B., & Akey, J. M. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.01.006 · Cited by 149 · see citing works
Sams, A. J., Dumaine, A., Nédélec, Y., Yotova, V., Alfieri, C., Tanner, J. E., Messer, P. W., & Barreiro, L. B. (2016) · Genome Biology · doi:10.1186/s13059-016-1098-6 · Cited by 140 · see citing works
Deleterious variation shapes the genomic landscape of introgression
Kim, B. Y., Huber, C. D., & Lohmueller, K. E. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007741 · Cited by 117 · see citing works
Neandertal Origin of Genetic Variation at the Cluster of OAS Immunity Genes
Mendez, F. L., Watkins, J. C., & Hammer, M. F. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst004 · Cited by 113 · see citing works
Wang, L., Chen, R., Liu, J. W., Lee, I., Lee, C.-P., Kuo, H., Huang, S. K., & Yang, K. D. (2011) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000934 · Cited by 107 · see citing works
The diverse origins of the human gene pool
Pääbo, S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3954 · Cited by 84 · see citing works
Kim, B. Y., & Lohmueller, K. E. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.12.029 · Cited by 82 · see citing works
Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition
Houldcroft, C. J., & Underdown, S. (2016) · American Journal of Physical Anthropology · doi:10.1002/ajpa.22985 · Cited by 75 · see citing works
Luisi, P., Alvarez‐Ponce, D., Pybus, M., Fares, M. A., Bertranpetit, J., & Laayouni, H. (2015) · Genome Biology and Evolution · doi:10.1093/gbe/evv055 · Cited by 59 · see citing works
Jagoda, E., Lawson, D. J., Wall, J. D., Lambert, D. M., Muller, C., Westaway, M., Leavesley, M., Capellini, T. D., Lahr, M. M., Gerbault, P., et al. (2017) · Molecular Biology and Evolution · doi:10.1093/molbev/msx314 · Cited by 57 · see citing works
Reuven, E. M., Ali, M., Rotem, E., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004248 · Cited by 36 · see citing works
Ryan, E. J., Dring, M. M., Ryan, C. M., McNulty, C., Stevenson, N. J., Lawless, M. W., Crowe, J., Nolan, N. P., Hegarty, J. E., & O’Farrelly, C. (2010) · Human Immunology · doi:10.1016/j.humimm.2010.05.007 · Cited by 31 · see citing works
Wang, Z., Liu, X., Zhao, Z., Xu, C., Zhang, K., Chen, C., Sun, L., Gao, G. F., Ye, X., & Liu, W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022625 · Cited by 31 · see citing works
High rate of adaptation of mammalian proteins that interact with Plasmodium and related parasites
Ebel, E. R., Telis, N., Venkataram, S., Petrov, D. A., & Enard, D. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007023 · Cited by 28 · see citing works
Self-citationVillanea, F. A., & Schraiber, J. G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/343087 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Kim BY, Huber CD, and Lohmueller KE (2017). Deleterious variation mimics signatures of genomic incompatibility and adaptive introgression. bioRxiv.
Cited by
Sorted by citations
The inflated significance of neutral genetic diversity in conservation genetics
Teixeira, J. C., & Huber, C. D. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2015096118 · Cited by 474 · see citing works
The influence of evolutionary history on human health and disease
Benton, M. L., Abraham, A., LaBella, A. L., Abbot, P., Rokas, A., & Capra, J. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00305-9 · Cited by 291 · see citing works
Genomic insights into population history and biological adaptation in Oceania
Choin, J., Mendoza-Revilla, J., Arauna, L. R., Cuadros-Espinoza, S., Cassar, O., Larena, M., Ko, A. M.-S., Harmant, C., Laurent, R., Verdu, P., et al. (2021) · Nature · doi:10.1038/s41586-021-03236-5 · Cited by 208 · see citing works
Human immune diversity: from evolution to modernity
Liston, A., Humblet-Baron, S., Duffy, D., & Goris, A. (2021) · Nature Immunology · doi:10.1038/s41590-021-01058-1 · Cited by 187 · see citing works
Quantifying the contribution of Neanderthal introgression to the heritability of complex traits
McArthur, E., Rinker, D. C., & Capra, J. A. (2021) · Nature Communications · doi:10.1038/s41467-021-24582-y · Cited by 71 · see citing works
Gouy, A., & Excoffier, L. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msz306 · Cited by 63 · see citing works
Silvert, M., Quintana-Murci, L., & Rotival, M. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.04.016 · Cited by 58 · see citing works
Selection against archaic hominin genetic variation in regulatory regions
Telis, N., Aguilar, R., & Harris, K. (2020) · Nature Ecology & Evolution · doi:10.1038/s41559-020-01284-0 · Cited by 51 · see citing works
The lingering effects of Neanderthal introgression on human complex traits
Wei, X., Robles, C. R., Pazokitoroudi, A., Ganna, A., Gusev, A., Durvasula, A., Gazal, S., Loh, P.-R., Reich, D., & Sankararaman, S. (2023) · eLife · doi:10.7554/elife.80757 · Cited by 43 · see citing works
Denisovan introgression has shaped the immune system of present-day Papuans
Vespasiani, D. M., Jacobs, G. S., Cook, L. E., Brucato, N., Leavesley, M., Kinipi, C., Ricaut, F.-X., Cox, M. P., & Gallego Romero, I. (2022) · PLOS Genetics · doi:10.1371/journal.pgen.1010470 · Cited by 46 · see citing works
Zhang, X., Kim, B., Singh, A., Sankararaman, S., Durvasula, A., & Lohmueller, K. E. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad001 · Cited by 29 · see citing works
- Authors
- Enard, D., & Petrov, D. A.
- Affiliations
- University of Arizona (US)
- Stanford University (US)
- Corresponding author
- Enard, David
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 2
- Pages
- 360-371.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6176737
- OpenAlex
- W2895121177
- Cited by
- 208
- References
- 52
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 26 · 2023: 31 · 2022: 23 · 2021: 39 · 2020: 26 · 2019: 30 · 2018: 7
- FWCI
- 107.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (1RO1GM10036601, R35GM118165)
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- Neanderthal admixture, adaptive introgression, Neanderthal ancestry, RNA viruses, host-virus interaction, purifying selection, ancient epidemics
- MeSH terms
- Alleles, Animals, Biological Evolution, Haplotypes, Humans, Hybridization, Genetic, Phylogeny, RNA Viruses, Selection, Genetic, Hominidae, Genome, Human, Neanderthals
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
