Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes
Open accessAbstract
Human genes governing innate immunity provide a valuable tool for the study of the selective pressure imposed by microorganisms on host genomes. A comprehensive, genome-wide study of how selective constraints and adaptations have driven the evolution of innate immunity genes is missing. Using full-genome sequence variation from the 1000 Genomes Project, we first show that innate immunity genes have globally evolved under stronger purifying selection than the remainder of protein-coding genes. We identify a gene set under the strongest selective constraints, mutations in which are likely to predispose individuals to life-threatening disease, as illustrated by STAT1 and TRAF3. We then evaluate the occurrence of local adaptation and detect 57 high-scoring signals of positive selection at innate immunity genes, variation in which has been associated with susceptibility to common infectious or autoimmune diseases. Furthermore, we show that most adaptations targeting coding variation have occurred in the last 6,000-13,000 years, the period at which populations shifted from hunting and gathering to farming. Finally, we show that innate immunity genes present higher Neandertal introgression than the remainder of the coding genome. Notably, among the genes presenting the highest Neandertal ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival and reveals others that are more permissive to change-containing variation acquired from archaic hominins or adaptive variants in specific populations-improving our understanding of the relative biological importance of innate immunity pathways in natural conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Neanderthal variants within immune genes and immune-related CREs have been associated with differential responses to viral infections among present-day Europeans.
“Neanderthal variants within immune genes and immune-related cis-regulatory elements (CREs) have been associated with differential responses to viral infections among present-day Europeans [21, 22].”
From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [21]
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 [2]
Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · see citing works
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816 · see citing works
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
An integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711 · see citing works
A general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183 · see citing works
A second generation human haplotype map of over 3.1 million SNPs
The International HapMap Consortium (2007) · Nature · doi:10.1038/nature06258 · Cited by 4,438 · see citing works
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
Approximate Bayesian computation in population genetics
Beaumont, M. A., Zhang, W., & Balding, D. J. (2002) · Genetics · doi:10.1093/genetics/162.4.2025 · Cited by 2,932 · see citing works
A Map of Recent Positive Selection in the Human Genome
Voight, B. F., Kudaravalli, S., Wen, X., & Pritchard, J. K. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040072 · Cited by 2,912 · see citing works
Genome-wide detection and characterization of positive selection in human populations
The International HapMap Consortium, Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., Xie, X., Byrne, E. H., McCarroll, S. A., et al. (2007) · Nature · doi:10.1038/nature06250 · Cited by 2,131 · see citing works
Genetic history of an archaic hominin group from Denisova Cave in Siberia
Reich, D., Green, R. E., Kircher, M., Krause, J., Patterson, N., Durand, E. Y., Viola, B., Briggs, A. W., Stenzel, U., Johnson, P. L. F., et al. (2010) · Nature · doi:10.1038/nature09710 · Cited by 1,991 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Origins of major human infectious diseases
Wolfe, N. D., Dunavan, C. P., & Diamond, J. (2007) · Nature · doi:10.1038/nature05775 · Cited by 1,867 · see citing works
Computing topological parameters of biological networks
Assenov, Y., Ramírez, F., Schelhorn, S.-E., Lengauer, T., & Albrecht, M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm554 · Cited by 1,805 · see citing works
Convergent adaptation of human lactase persistence in Africa and Europe
Tishkoff, S. A., Reed, F. A., Ranciaro, A., Voight, B. F., Babbitt, C. C., Silverman, J. S., Powell, K., Mortensen, H. M., Hirbo, J. B., Osman, M., et al. (2007) · Nature Genetics · doi:10.1038/ng1946 · Cited by 1,615 · see citing works
Genome-wide patterns of selection in 230 ancient Eurasians
Mathieson, I., Lazaridis, I., Rohland, N., Mallick, S., Patterson, N., Roodenberg, S. A., Harney, E., Stewardson, K., Fernandes, D., Novak, M., et al. (2015) · Nature · doi:10.1038/nature16152 · Cited by 1,515 · see citing works
Genetics in geographically structured populations: defining, estimating and interpreting FST
Holsinger, K. E., & Weir, B. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2611 · Cited by 1,422 · see citing works
Brass, A., Huang, I.-C., Benita, Y., John, S., Krishnan, M. N., Feeley, E., Ryan, B., Weyer, J., van der Weyden, L., Fikrig, E., et al. (2009) · Cell · doi:10.1016/j.cell.2009.12.017 · Cited by 1,292 · see citing works
InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation
Breuer, K., Foroushani, A. B. K., Laird, M. R., Chen, C. C. L., Sribnaia, A., Lo, R., Winsor, G. L., Hancock, R. E. W., Brinkman, F. S. L., & Lynn, D. J. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1147 · Cited by 1,224 · see citing works
Pïcard, C., Al–Herz, W., Bousfiha, A. A., et al. (2015) · Journal of Clinical Immunology · doi:10.1007/s10875-015-0201-1 · Cited by 1,200 · 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
Genetic signatures of strong recent positive selection at the lactase gene.
Bersaglieri, T., Sabeti, P. C., Patterson, N., VanderPloeg, T., Schaffner, S., Drake, J. A., Rhodes, M., Reich, D., & Hirschhorn, J. (2004) · American Journal of Human Genetics · doi:10.1086/421051 · Cited by 1,098 · see citing works
Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences
Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., Shen-Orr, S., Dekker, C. L., Swan, G. E., Butte, A. J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.020 · Cited by 1,065 · see citing works
Farmers and Their Languages: The First Expansions
Diamond, J., & Bellwood, P. (2003) · Science · doi:10.1126/science.1078208 · Cited by 1,054 · see citing works
The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation
Pritchard, J. K., Pickrell, J. K., & Coop, G. (2010) · Current Biology · doi:10.1016/j.cub.2009.11.055 · Cited by 932 · cited 1× · see citing works
“We simulated neutrally evolving regions and positive selection assuming the hard sweep model.(60) Specifically, a single new advantageous mutation with”
The BioGRID interaction database: 2015 update
Chatr‐aryamontri, A., Breitkreutz, B., Oughtred, R., Boucher, L., Heinicke, S., Chen, D., Stark, C., Breitkreutz, A., Kolas, N. K., O’Donnell, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1204 · Cited by 884 · see citing works
CD36 is a sensor of diacylglycerides
Hoebe, K., Georgel, P., Rutschmann, S., Du, X., Mudd, S., Crozat, K., Sovath, S., Shamel, L., Hartung, T., Zähringer, U., et al. (2005) · Nature · doi:10.1038/nature03253 · Cited by 873 · see citing works
Evolutionary Rate in the Protein Interaction Network
Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Scharfe, C., & Feldman, M. W. (2002) · Science · doi:10.1126/science.1068696 · Cited by 869 · see citing works
Natural selection on protein-coding genes in the human genome
Bustamante, C. D., Fledel-Alon, A., Williamson, S., Nielsen, R., Hubisz, M. J., Glanowski, S., Tanenbaum, D. M., White, T. J., Sninsky, J. J., Hernandez, R. D., et al. (2005) · Nature · doi:10.1038/nature04240 · Cited by 788 · see citing works
IFITM3 restricts the morbidity and mortality associated with influenza
The GenISIS Investigators, Everitt, A. R., The MOSAIC Investigators, Clare, S., Pertel, T., John, S. P., Wash, R. S., Smith, S. E., Chin, C. R., Feeley, E. M., et al. (2012) · Nature · doi:10.1038/nature10921 · Cited by 783 · see citing works
Al–Herz, W., Bousfiha, A. A., Casanova, J., Chatila, T. A., Conley, M. E., Cunningham‐Rundles, C., Etzioni, A., Franco, J. L., Gaspar, H. B., Holland, S. M., et al. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00162 · Cited by 769 · see citing works
Self-citationInnate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression
Fairfax, B. P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C., et al. (2014) · Science · doi:10.1126/science.1246949 · Cited by 764 · see citing works
Signals of recent positive selection in a worldwide sample of human populations
Pickrell, J. K., Coop, G., Novembre, J., Kudaravalli, S., Li, J. Z., Absher, D., Srinivasan, B. S., Barsh, G. S., Myers, R. M., Feldman, M. W., et al. (2009) · Genome Research · doi:10.1101/gr.087577.108 · Cited by 717 · see citing works
Comparative Genomics of Centrality and Essentiality in Three Eukaryotic Protein-Interaction Networks
Hahn, M. W., & Kern, A. D. (2005) · Molecular Biology and Evolution · doi:10.1093/molbev/msi072 · Cited by 656 · see citing works
Natural selection has driven population differentiation in modern humans
Barreiro, L. B., Laval, G., Quach, H., Patin, E., & Quintana-Murci, L. (2008) · Nature Genetics · doi:10.1038/ng.78 · Cited by 605 · see citing works
Self-citationFumagalli, M., Sironi, M., Pozzoli, U., Ferrer-Admettla, A., Pattini, L., & Nielsen, R. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002355 · Cited by 600 · see citing works
The Origins of Lactase Persistence in Europe
Itan, Y., Powell, A., Beaumont, M. A., Burger, J., & Thomas, M. G. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000491 · Cited by 569 · see citing works
Self-citationFrom evolutionary genetics to human immunology: how selection shapes host defence genes
Barreiro, L. B., & Quintana‐Murci, L. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2698 · Cited by 556 · see citing works
Self-citationThe 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
Natural selection and infectious disease in human populations
Karlsson, E. K., Kwiatkowski, D. P., & Sabeti, P. C. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3734 · Cited by 526 · see citing works
A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection
Grossman, S. R., Shylakhter, I., Karlsson, E. K., Byrne, E. H., Morales, S., Frieden, G., Hostetter, E., Angelino, E., Garber, M., Zuk, O., et al. (2010) · Science · doi:10.1126/science.1183863 · Cited by 512 · see citing works
Recent and ongoing selection in the human genome
Nielsen, R., Hellmann, I., Hubisz, M. J., Bustamante, C. D., & Clark, A. G. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2187 · Cited by 501 · see citing works
Human genetic susceptibility to infectious disease
Chapman, S. J., & Hill, A. V. S. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3114 · Cited by 499 · see citing works
Population genomics of rapid adaptation by soft selective sweeps
Messer, P. W., & Petrov, D. A. (2013) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2013.08.003 · Cited by 475 · see citing works
The role of geography in human adaptation
Coop, G., Pickrell, J. K., Novembre, J., Kudaravalli, S., Li, J., Absher, D., Myers, R. M., Cavalli-Sforza, L. L., Feldman, M. W., & Pritchard, J. K. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000500 · Cited by 412 · see citing works
Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense
Barreiro, L. B., Ben‐Ali, M., Quach, H., Laval, G., Patin, É., Pickrell, J. K., Bouchier, C., Tichit, M., Neyrolles, O., Gicquel, B., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000562 · Cited by 392 · see citing works
Self-citationIdentifying Recent Adaptations in Large-Scale Genomic Data
Grossman, S. R., Andersen, K. G., Shlyakhter, I., Tabrizi, S., Winnicki, S., Yen, A., Park, D. J., Griesemer, D., Karlsson, E. K., Wong, S. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.035 · Cited by 368 · see citing works
de Diego, R. P., Sancho‐Shimizu, V., Lorenzo, L., Puel, A., Plancoulaine, S., Pïcard, C., Casadio, M., Cardon, A., Durandy, A., Bustamante, J. C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.014 · Cited by 348 · see citing works
Self-citationMultiple Instances of Ancient Balancing Selection Shared Between Humans and Chimpanzees
Leffler, E. M., Gao, Z., Pfeifer, S. P., Ségurel, L., Auton, A., Venn, O., Bowden, R. J., Bontrop, R. E., Wall, J. D., Sella, G., et al. (2013) · Science · doi:10.1126/science.1234070 · Cited by 326 · see citing works
TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans
Ferwerda, B., McCall, M. B. B., Alonso, S., Giamarellos‐Bourboulis, E. J., Mouktaroudi, M., Izagirre, N., Syafruddin, D., Kibiki, G. S., Cristea, T., Hijmans, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704828104 · Cited by 319 · see citing works
Boisson‐Dupuis, S., Kong, X., Okada, S., Cypowyj, S., Puel, A., Abel, L., & Casanova, J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.011 · Cited by 287 · see citing works
Self-citationJohnson, C. M., Lyle, E. A., Ayoade, K. O., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7520 · Cited by 265 · see citing works
A Natural History of FUT2 Polymorphism in Humans
Ferrer-Admetlla, A., Sikora, M., Laayouni, H., Esteve‐Codina, A., Roubinet, F., Blancher, A., Calafell, F., Bertranpetit, J., & Casals, F. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp108 · Cited by 249 · see citing works
Patterns of coding variation in the complete exomes of three Neandertals
Castellano, S., Parra, G., Sánchez-Quinto, F. A., Racimo, F., Kuhlwilm, M., Kircher, M., Sawyer, S., Fu, Q., Heinze, A., Nickel, B., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405138111 · Cited by 247 · see citing works
Hinds, D. A., McMahon, G., Kiefer, A. K., Do, C. B., Eriksson, N., Evans, D. M., St Pourcain, B., Ring, S. M., Mountain, J. L., Francke, U., et al. (2013) · Nature Genetics · doi:10.1038/ng.2686 · Cited by 246 · see citing works
Australian Asthma Genetics Consortium (AAGC), Bønnelykke, K., the EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Matheson, M. C., Pers, T. H., Granell, R., Strachan, D. P., Alves, A. C., Linneberg, A., Curtin, J. A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2694 · Cited by 244 · see citing works
Natural Selection on Genes that Underlie Human Disease Susceptibility
Blekhman, R., Man, O., Herrmann, L., Boyko, A. R., Indap, A. R., Kosiol, C., Bustamante, C. D., Teshima, K. M., & Przeworski, M. (2008) · Current Biology · doi:10.1016/j.cub.2008.04.074 · Cited by 222 · see citing works
Reappraisal of known malaria resistance loci in a large multicenter study
Malaria Genomic Epidemiology Network, Rockett, K. A., Clarke, G. M., Fitzpatrick, K., Hubbart, C., Jeffreys, A. E., Rowlands, K., Craik, R., Jallow, M., Conway, D. J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3107 · Cited by 222 · see citing works
The Effect of the Host’s Iron Status on Tuberculosis
Boelaert, J. R., Vandecasteele, S. J., Appelberg, R., & Gordeuk, V. R. (2007) · The Journal of Infectious Diseases · doi:10.1086/518040 · Cited by 217 · see citing works
Ferreira, M. A. R., Matheson, M. C., Tang, C. S., Granell, R., Ang, W., Hui, J., Kiefer, A. K., Duffy, D. L., Baltic, S., Danoy, P., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.10.030 · Cited by 216 · see citing works
Distinguishing between selective sweeps from standing variation and from a de novo mutation
Peter, B. M., Huerta-Sanchez, E., & Nielsen, R. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003011 · Cited by 193 · see citing works
Balancing Selection Is the Main Force Shaping the Evolution of Innate Immunity Genes
Ferrer-Admetlla, A., Bosch, E., Sikora, M., Marquès‐Bonet, T., Ramírez-Soriano, A., Muntasell, A., Navarro, A., Lazarus, R. M., Calafell, F., Bertranpetit, J., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.1315 · Cited by 187 · see citing works
Inborn errors of immunity to infection
Casanova, J., & Abel, L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050854 · Cited by 187 · see citing works
Self-citationLife‐threatening infectious diseases of childhood: single‐gene inborn errors of immunity?
Alcaïs, A., Quintana‐Murci, L., Thaler, D. S., Schurr, E., Abel, L., & Casanova, J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05834.x · Cited by 180 · see citing works
Self-citationGenome-wide association study of ancestry-specific TB risk in the South African Coloured population
Chimusa, E. R., Zaitlen, N., Daya, M., Möller, M., van Helden, P. D., Mulder, N., Price, A. L., & Hoal, E. G. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt462 · Cited by 178 · see citing works
Evidence for Polygenic Adaptation to Pathogens in the Human Genome
Daub, J. T., Hofer, T., Cutivet, E., Dupanloup, I., Quintana‐Murci, L., Robinson‐Rechavi, M., & Excoffier, L. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst080 · Cited by 178 · see citing works
Self-citationPatin, É., Kutalik, Z., Guergnon, J., Bibert, S., Nalpas, B., Jouanguy, E., Munteanu, M., Bousquet, L., Argiro, L., Halfon, P., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.07.097 · Cited by 176 · see citing works
Self-citationAdaptation and Constraint at Toll-Like Receptors in Primates
Wlasiuk, G., & Nachman, M. W. (2010) · Molecular Biology and Evolution · doi:10.1093/molbev/msq104 · Cited by 176 · see citing works
Evolutionary genetic dissection of human interferons
Manry, J., Laval, G., Patin, E., Fornarino, S., Itan, Y., Fumagalli, M., Sironi, M., Tichit, M., Bouchier, C., Casanova, J.-L., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20111680 · Cited by 176 · see citing works
Self-citationCytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum
Newbold, C., Craig, A. G., Kyes, S., Rowe, J. A., Fernández-Reyes, D., & Fagan, T. (1999) · International Journal for Parasitology · doi:10.1016/s0020-7519(99)00049-1 · Cited by 168 · 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
Misch, E. A., Macdonald, M., Ranjit, C., Sapkota, B. R., Wells, R. D., Siddiqui, R., Kaplan, G., & Hawn, T. R. (2008) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000231 · Cited by 142 · see citing works
Population genetic tools for dissecting innate immunity in humans
Quintana‐Murci, L., & Clark, A. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3421 · Cited by 141 · see citing works
Self-citationIntegrating and annotating the interactome using the MiMI plugin for cytoscape
Gao, J., Ade, A. S., Tarcea, V. G., Weymouth, T. E., Mirel, B. R., Jagadish, H. V., & States, D. J. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn501 · Cited by 125 · see citing works
Advantageous diversity maintained by balancing selection in humans
Key, F. M., Teixeira, J. C., de Filippo, C., & Andrés, A. M. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.08.001 · Cited by 120 · see citing works
Mukherjee, S., Sarkar-Roy, N., Wagener, D. K., & Majumder, P. P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811357106 · Cited by 120 · see citing works
Al–Herz, W., Bousfiha, A. A., Casanova, J., et al. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00460 · Cited by 119 · see citing works
Self-citationNeandertal 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
A Novel Approach for Choosing Summary Statistics in Approximate Bayesian Computation
Aeschbacher, S., Beaumont, M., & Futschik, A. (2012) · Genetics · doi:10.1534/genetics.112.143164 · Cited by 106 · see citing works
Laayouni, H., Oosting, M., Luisi, P., Ioana, M. I., Alonso, S., Ricaño-Ponce, I., Trynka, G., Zhernakova, A., Plantinga, T. S., Cheng, S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317723111 · Cited by 96 · see citing works
SnIPRE: Selection Inference Using a Poisson Random Effects Model
Eilertson, K. E., Booth, J. G., & Bustamante, C. D. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002806 · Cited by 95 · see citing works
Bhatia, G., Patterson, N. J., Paşaniuc, B., Zaitlen, N., Genovese, G., Pollack, S. J., Mallick, S., Myers, S., Tandon, A., Spencer, C. C. A., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.07.025 · Cited by 85 · see citing works
Pybus, M., Luisi, P., Dall’Olio, G. M., Uzkudun, M., Laayouni, H., Bertranpetit, J., & Engelken, J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv493 · Cited by 83 · see citing works
Colonna, V., Ayub, Q., Chen, Y., Pagani, L., Luisi, P., Pybus, M., Garrison, E. P., Xue, Y., & Tyler‐Smith, C. (2014) · Genome biology · doi:10.1186/gb-2014-15-6-r88 · Cited by 80 · see citing works
Fry, A. E., Ghansa, A., Small, K. S., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp192 · Cited by 77 · see citing works
Fagny, M., Patin, É., Enard, D., Barreiro, L. B., Quintana‐Murci, L., & Laval, G. (2014) · Molecular Biology and Evolution · doi:10.1093/molbev/msu118 · Cited by 74 · see citing works
Self-citationHuman and Non-Human Primate Genomes Share Hotspots of Positive Selection
Enard, D., Depaulis, F., & Crollius, H. R. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000840 · Cited by 70 · see citing works
Immunology Taught by Human GeneticsPreprint
Casanova, J., Abel, L., & Quintana‐Murci, L. (2013) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2013.78.019968 · Cited by 70 · see citing works
Self-citationDirectional and balancing selection in human beta-defensins
Hollox, E. J., & Armour, J. A. L. (2008) · BMC Evolutionary Biology · doi:10.1186/1471-2148-8-113 · Cited by 67 · see citing works
Human genome variability, natural selection and infectious diseases
Fumagalli, M., & Sironi, M. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.001 · Cited by 66 · see citing works
Cosi2: an efficient simulator of exact and approximate coalescent with selection
Shlyakhter, I. A., Sabeti, P. C., & Schaffner, S. F. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu562 · Cited by 51 · see citing works
The selective footprints of viral pressures at the human RIG-I-like receptor family
Vasseur, E., Patin, É., Laval, G., Pajon, S., Fornarino, S., Crouau‐Roy, B., & Quintana‐Murci, L. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr377 · Cited by 49 · see citing works
Self-citationFumagalli, M., Cagliani, R., Riva, S., Pozzoli, U., Biasin, M., Piacentini, L., Comi, G. P., Bresolin, N., Clerici, M., & Sironi, M. (2010) · Molecular Biology and Evolution · doi:10.1093/molbev/msq141 · Cited by 48 · see citing works
Fornarino, S., Laval, G., Barreiro, L. B., Manry, J., Vasseur, E., & Quintana‐Murci, L. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msr137 · Cited by 46 · see citing works
Self-citationThe Evolutionary Landscape of Cytosolic Microbial Sensors in Humans
Vasseur, E., Boniotto, M., Patin, É., Laval, G., Quach, H., Manry, J., Crouau‐Roy, B., & Quintana‐Murci, L. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.05.008 · Cited by 37 · see citing works
Self-citationAncient and Recent Selective Pressures Shaped Genetic Diversity at AIM2-Like Nucleic Acid Sensors
Cagliani, R., Forni, D., Biasin, M., Comabella, M., Guerini, F. R., Riva, S., Pozzoli, U., Agliardi, C., Caputo, D., Malhotra, S., et al. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu066 · Cited by 32 · see citing works
Genetic adaptation of the antibacterial human innate immunity network
Casals, F., Sikora, M., Laayouni, H., Montanucci, L., Muntasell, A., Lazarus, R. M., Calafell, F., Awadalla, P., Netea, M. G., & Bertranpetit, J. (2011) · BMC Evolutionary Biology · doi:10.1186/1471-2148-11-202 · Cited by 28 · see citing works
Disentangling Inborn and Acquired Immunity in Human Twins
Casanova, J., & Abel, L. (2015) · Cell · doi:10.1016/j.cell.2014.12.029 · Cited by 21 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Genetic determinants of the gut microbiome in UK twins
Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, M. A., Knight, R., Ober, C., Spector, T. D., Bell, J. T., Clark, A. G., & Ley, R. E. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.04.017 · Cited by 1,048 · 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
Self-citationAnalysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture
Browning, S. R., Browning, B. L., Zhou, Y., Tucci, S., & Akey, J. M. (2018) · Cell · doi:10.1016/j.cell.2018.02.031 · Cited by 381 · see citing works
The <scp>AIM</scp>2 inflammasome: Sensor of pathogens and cellular perturbations
Lugrin, J., & Martinon, F. (2018) · Immunological Reviews · doi:10.1111/imr.12618 · Cited by 333 · 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
Neanderthal language revisited: not only us
Dediu, D., & Levinson, S. C. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.01.001 · Cited by 218 · 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
Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans
Enard, D., & Petrov, D. A. (2018) · Cell · doi:10.1016/j.cell.2018.08.034 · Cited by 208 · 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
Self-citationImpacts of Neanderthal-Introgressed Sequences on the Landscape of Human Gene Expression
McCoy, R. C., Wakefield, J., & Akey, J. M. (2017) · Cell · doi:10.1016/j.cell.2017.01.038 · Cited by 200 · 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
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
Functional implications of Neandertal introgression in modern humans
Dannemann, M., Prüfer, K., & Kelso, J. (2017) · Genome biology · doi:10.1186/s13059-017-1181-7 · Cited by 92 · see citing works
Human evolution: a tale from ancient genomes
Llamas, B., Willerslev, E., & Orlando, L. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0484 · Cited by 100 · see citing works
Something old, something borrowed: admixture and adaptation in human evolution
Dannemann, M., & Racimo, F. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.05.009 · Cited by 87 · 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
Signatures of archaic adaptive introgression in present-day human populations
Racimo, F., Marnetto, D., & Huerta-Sánchez, E. (2016) · doi:10.1101/045237 · Cited by 200 · see citing works
Gouy, A., & Excoffier, L. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msz306 · Cited by 63 · see citing works
Hawash, M. B. F., Sanz-Remón, J., Grenier, J.-C., Kohn, J., Yotova, V., Johnson, Z., Lanford, R. E., Brinkworth, J. F., & Barreiro, L. B. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2015855118 · Cited by 56 · 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
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
“As above, repeating this analysis in Neanderthal aSNPs segregating within Europeans also identified significant enrichments of Neanderthal aSNPs within CREs active in mesenchymal and blood & T cells (S6(B) Fig).”
InfluentialZhang, 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
Evolutionary and medical consequences of archaic introgression into modern human genomes
Dolgova, O., & Lao, O. (2018) · Genes · doi:10.3390/genes9070358 · Cited by 34 · see citing works
Chintalapati, M., Dannemann, M., & Prüfer, K. (2017) · BMC Evolutionary Biology · doi:10.1186/s12862-017-1018-8 · Cited by 13 · see citing works
- Authors
- Deschamps, M., Laval, G., Fagny, M., Itan, Y., Abel, L., Casanova, J.-L., Patin, E., & Quintana-Murci, L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Rockefeller University (US)
- Inserm (FR)
- Hôpital Necker-Enfants Malades (FR)
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 98
- Issue
- 1
- Pages
- 5-21
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4716683
- OpenAlex
- W2225153589
- Cited by
- 257
- References
- 100
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 24 · 2023: 18 · 2022: 28 · 2021: 24 · 2020: 23 · 2019: 27 · 2018: 26 · 2017: 33 · 2016: 22
- FWCI
- 29.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut national de la recherche scientifique
- Agence Nationale de la Recherche (ANR-14-CE14-0007, ANR-14-CE14-0008, ANR-12-BSV7-0012, ANR-10-LABX-0062)
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- innate immunity genes, purifying selection, positive selection, archaic humans, adaptive evolution, STAT1, TRAF3, local adaptation, disease susceptibility, transition to agriculture, host-pathogen coevolution
- MeSH terms
- Adaptation, Physiological, Animals, Humans, Immunity, Innate, Selection, Genetic, Polymorphism, Single Nucleotide, Genome-Wide Association Study, 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