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PMID: 23470320 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Population genetic tools for dissecting innate immunity in humans.

Nature reviews. Immunology ·Vol. 13 ·No. 4 ·2013-04-00 ·Pages 280-93

Quintana-Murci L, Clark AG

Abstract

Innate immunity involves direct interactions between the host and microorganisms, both pathogenic and symbiotic, so natural selection is expected to strongly influence genes involved in these processes. Population genetics investigates the impact of past natural selection events on the genome of present-day human populations, and it complements immunological as well as clinical and epidemiological genetic studies. Recent data show that the impact of selection on the different families of innate immune receptors and their downstream signalling molecules varies considerably. This Review discusses these findings and highlights how they help to delineate the relative functional importance of innate immune pathways, which can range from being essential to being redundant.

MeSH Terms
Evolution, Molecular Genetic Predisposition to Disease/genetics Genetics, Population/methods Genome, Human/genetics Humans Immunity, Innate/genetics Models, Genetic Models, Immunological Selection, Genetic
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Quintana-Murci Lluís
Institut Pasteur, Unit of Human Evolutionary Genetics, Paris, France. [email protected]
Clark Andrew G
References (158)
158 references, click to expand
  1. Whole-exome-sequencing-based discovery of human FADD deficiency.
    Am J Hum Genet. 2010 Dec 10;87(6):873-81 PMID: 21109225
  2. Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction.
    PLoS Negl Trop Dis. 2008 May 07;2(5):e231 PMID: 18461142
  3. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.
    Nat Genet. 2013 Feb;45(2):164-71 PMID: 23291588
  4. NLR functions beyond pathogen recognition.
    Nat Immunol. 2011 Feb;12(2):121-8 PMID: 21245903
  5. Evolution of the TIR domain-containing adaptors in humans: swinging between constraint and adaptation.
    Mol Biol Evol. 2011 Nov;28(11):3087-97 PMID: 21659570
  6. Genetic adaptation of the antibacterial human innate immunity network.
    BMC Evol Biol. 2011 Jul 11;11:202 PMID: 21745391
  7. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.
    Immunity. 2005 Aug;23(2):165-75 PMID: 16111635
  8. Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9.
    Semin Immunol. 2004 Feb;16(1):17-22 PMID: 14751759
  9. Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans.
    Genetics. 2001 Aug;158(4):1657-64 PMID: 11514453
  10. Population genetics of IFIH1: ancient population structure, local selection, and implications for susceptibility to type 1 diabetes.
    Mol Biol Evol. 2010 Nov;27(11):2555-66 PMID: 20538742
  11. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    Nature. 2012 Nov 1;491(7422):119-24 PMID: 23128233
  12. From evolutionary genetics to human immunology: how selection shapes host defence genes.
    Nat Rev Genet. 2010 Jan;11(1):17-30 PMID: 19953080
  13. Mannan-binding lectin deficiency - Good news, bad news, doesn't matter?
    Clin Immunol. 2012 Apr;143(1):22-38 PMID: 22377282
  14. Molecular population genetics of inducible antibacterial peptide genes in Drosophila melanogaster.
    Mol Biol Evol. 2003 Jun;20(6):914-23 PMID: 12716986
  15. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense.
    Immunol Rev. 2008 Dec;226:29-40 PMID: 19161414
  16. Evolutionary genetics evidence of an essential, nonredundant role of the IFN-γ pathway in protective immunity.
    Hum Mutat. 2011 Jun;32(6):633-42 PMID: 21448974
  17. Evolutionary processes acting on candidate cis-regulatory regions in humans inferred from patterns of polymorphism and divergence.
    PLoS Genet. 2009 Aug;5(8):e1000592 PMID: 19662163
  18. The lectin-complement pathway--its role in innate immunity and evolution.
    Immunol Rev. 2004 Apr;198:185-202 PMID: 15199963
  19. Signaling by myeloid C-type lectin receptors in immunity and homeostasis.
    Annu Rev Immunol. 2012;30:491-529 PMID: 22224766
  20. Inflammasomes in health and disease.
    Nature. 2012 Jan 18;481(7381):278-86 PMID: 22258606
  21. An interferon-gamma-related cytokine storm in SARS patients.
    J Med Virol. 2005 Feb;75(2):185-94 PMID: 15602737
  22. Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population.
    Genes Immun. 2007 Jul;8(5):439-43 PMID: 17508030
  23. The host defense of Drosophila melanogaster.
    Annu Rev Immunol. 2007;25:697-743 PMID: 17201680
  24. A history of recurrent positive selection at the toll-like receptor 5 in primates.
    Mol Biol Evol. 2009 Apr;26(4):937-49 PMID: 19179655
  25. Searching for signals of evolutionary selection in 168 genes related to immune function.
    Hum Genet. 2006 Mar;119(1-2):92-102 PMID: 16362345
  26. Proportionally more deleterious genetic variation in European than in African populations.
    Nature. 2008 Feb 21;451(7181):994-7 PMID: 18288194
  27. Dynamic evolution of the innate immune system in Drosophila.
    Nat Genet. 2007 Dec;39(12):1461-8 PMID: 17987029
  28. Directional and balancing selection in human beta-defensins.
    BMC Evol Biol. 2008 Apr 16;8:113 PMID: 18416833
  29. A map of human genome variation from population-scale sequencing.
    Nature. 2010 Oct 28;467(7319):1061-73 PMID: 20981092
  30. The inflammasomes.
    Cell. 2010 Mar 19;140(6):821-32 PMID: 20303873
  31. Contrasting evolutionary patterns in Drosophila immune receptors.
    J Mol Evol. 2006 Dec;63(6):769-80 PMID: 17103056
  32. Natural selection drives Drosophila immune system evolution.
    Genetics. 2003 Aug;164(4):1471-80 PMID: 12930753
  33. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.
    Nat Genet. 2009 Oct;41(10):1100-4 PMID: 19749758
  34. Mannose-binding protein B allele confers protection against tuberculous meningitis.
    Pediatr Res. 1999 Apr;45(4 Pt 1):459-64 PMID: 10203135
  35. Signals of recent positive selection in a worldwide sample of human populations.
    Genome Res. 2009 May;19(5):826-37 PMID: 19307593
  36. Pattern recognition receptors and inflammation.
    Cell. 2010 Mar 19;140(6):805-20 PMID: 20303872
  37. Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes.
    Science. 2007 Jun 22;316(5832):1738-43 PMID: 17588928
  38. Allelic recombination between distinct genomic locations generates copy number diversity in human beta-defensins.
    Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):853-8 PMID: 19131514
  39. The evolution and genetics of innate immunity.
    Nat Rev Genet. 2001 Apr;2(4):256-67 PMID: 11283698
  40. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
    Nat Rev Immunol. 2007 May;7(5):353-64 PMID: 17457343
  41. Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.
    Arthritis Rheum. 2002 Sep;46(9):2445-52 PMID: 12355493
  42. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis.
    Nature. 2008 Nov 27;456(7221):507-10 PMID: 18987631
  43. Immunology in natura: clinical, epidemiological and evolutionary genetics of infectious diseases.
    Nat Immunol. 2007 Nov;8(11):1165-71 PMID: 17952041
  44. Natural selection on genes that underlie human disease susceptibility.
    Curr Biol. 2008 Jun 24;18(12):883-9 PMID: 18571414
  45. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication.
    Science. 2006 Jun 16;312(5780):1669-72 PMID: 16709748
  46. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.
    Nature. 2009 Sep 17;461(7262):399-401 PMID: 19684573
  47. Human genetics of infectious diseases: a unified theory.
    EMBO J. 2007 Feb 21;26(4):915-22 PMID: 17255931
  48. Integrating common and rare genetic variation in diverse human populations.
    Nature. 2010 Sep 2;467(7311):52-8 PMID: 20811451
  49. Herpes simplex virus encephalitis in human UNC-93B deficiency.
    Science. 2006 Oct 13;314(5797):308-12 PMID: 16973841
  50. Targets of balancing selection in the human genome.
    Mol Biol Evol. 2009 Dec;26(12):2755-64 PMID: 19713326
  51. Balancing selection is the main force shaping the evolution of innate immunity genes.
    J Immunol. 2008 Jul 15;181(2):1315-22 PMID: 18606686
  52. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease.
    J Exp Med. 2003 Nov 17;198(10):1563-72 PMID: 14623910
  53. How do plants achieve immunity? Defence without specialized immune cells.
    Nat Rev Immunol. 2012 Jan 25;12(2):89-100 PMID: 22273771
  54. Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection.
    Genes Immun. 2004 Sep;5(6):461-76 PMID: 15306844
  55. Comparison of avian and human influenza A viruses reveals a mutational bias on the viral genomes.
    J Virol. 2006 Dec;80(23):11887-91 PMID: 16987977
  56. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis.
    J Exp Med. 2011 Aug 1;208(8):1635-48 PMID: 21727188
  57. Pyogenic bacterial infections in humans with MyD88 deficiency.
    Science. 2008 Aug 1;321(5889):691-6 PMID: 18669862
  58. The evolution of antifungal peptides in Drosophila.
    Genetics. 2005 Dec;171(4):1847-59 PMID: 16157672
  59. Elevated polymorphism and divergence in the class C scavenger receptors of Drosophila melanogaster and D. simulans.
    Genetics. 2005 Apr;169(4):2023-34 PMID: 15716507
  60. Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics.
    Annu Rev Immunol. 2011;29:447-91 PMID: 21219179
  61. Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.
    Genetics. 2000 Mar;154(3):1231-8 PMID: 10757765
  62. Human and non-human primate genomes share hotspots of positive selection.
    PLoS Genet. 2010 Feb 05;6(2):e1000840 PMID: 20140238
  63. Toll-like receptors in systemic autoimmune disease.
    Nat Rev Immunol. 2006 Nov;6(11):823-35 PMID: 17063184
  64. Population genetics models of common diseases.
    Curr Opin Genet Dev. 2006 Dec;16(6):630-6 PMID: 17055247
  65. Collections and ficolins: humoral lectins of the innate immune defense.
    Annu Rev Immunol. 2003;21:547-78 PMID: 12524383
  66. Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation.
    Mol Biol Evol. 2012 Jun;29(6):1569-85 PMID: 22319155
  67. Genome-wide detection and characterization of positive selection in human populations.
    Nature. 2007 Oct 18;449(7164):913-8 PMID: 17943131
  68. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.
    Nat Rev Immunol. 2007 Nov;7(11):862-74 PMID: 17948019
  69. Constructing genomic maps of positive selection in humans: where do we go from here?
    Genome Res. 2009 May;19(5):711-22 PMID: 19411596
  70. A -defensin mutation causes black coat color in domestic dogs.
    Science. 2007 Nov 30;318(5855):1418-23 PMID: 17947548
  71. Carriers of rare missense variants in IFIH1 are protected from psoriasis.
    J Invest Dermatol. 2010 Dec;130(12):2768-72 PMID: 20668468
  72. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.
    Nat Genet. 2012 May 06;44(6):676-80 PMID: 22561518
  73. Gene expression levels are a target of recent natural selection in the human genome.
    Mol Biol Evol. 2009 Mar;26(3):649-58 PMID: 19091723
  74. Comparative genomics and evolution of the alpha-defensin multigene family in primates.
    Mol Biol Evol. 2010 Oct;27(10):2333-43 PMID: 20457584
  75. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?
    Ann N Y Acad Sci. 2010 Dec;1214:18-33 PMID: 21091717
  76. Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles.
    Hum Mol Genet. 2006 Sep 1;15(17):2650-8 PMID: 16885193
  77. Natural selection on protein-coding genes in the human genome.
    Nature. 2005 Oct 20;437(7062):1153-7 PMID: 16237444
  78. A map of recent positive selection in the human genome.
    PLoS Biol. 2006 Mar;4(3):e72 PMID: 16494531
  79. The evolution of adaptive immune systems.
    Cell. 2006 Feb 24;124(4):815-22 PMID: 16497590
  80. Positive natural selection in the human lineage.
    Science. 2006 Jun 16;312(5780):1614-20 PMID: 16778047
  81. NALP1 in vitiligo-associated multiple autoimmune disease.
    N Engl J Med. 2007 Mar 22;356(12):1216-25 PMID: 17377159
  82. Human genetic susceptibility to intracellular pathogens.
    Immunol Rev. 2011 Mar;240(1):105-16 PMID: 21349089
  83. An integrated view of humoral innate immunity: pentraxins as a paradigm.
    Annu Rev Immunol. 2010;28:157-83 PMID: 19968561
  84. The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates.
    Genes Immun. 2008 Sep;9(6):483-92 PMID: 18528403
  85. Human genetics of infectious diseases: between proof of principle and paradigm.
    J Clin Invest. 2009 Sep;119(9):2506-14 PMID: 19729848
  86. Impact of mannose-binding lectin on susceptibility to infectious diseases.
    Clin Infect Dis. 2003 Dec 1;37(11):1496-505 PMID: 14614673
  87. Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children.
    Genes Immun. 2006 Jan;7(1):59-64 PMID: 16435024
  88. Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions.
    J Infect Dis. 2009 Jun 15;199(12):1816-9 PMID: 19456232
  89. Natural selection in the TLR-related genes in the course of primate evolution.
    Immunogenetics. 2008 Dec;60(12):727-35 PMID: 18810425
  90. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction.
    Nat Genet. 2005 May;37(5):486-94 PMID: 15821736
  91. Association between deficiency of mannose-binding lectin and severe infections after chemotherapy.
    Lancet. 2001 Aug 25;358(9282):637-8 PMID: 11530153
  92. Nucleic acid-sensing TLRs as modifiers of autoimmunity.
    J Immunol. 2006 Nov 15;177(10):6573-8 PMID: 17082566
  93. Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma.
    J Exp Med. 2010 Oct 25;207(11):2307-12 PMID: 20876309
  94. The genetics and immunopathogenesis of inflammatory bowel disease.
    Nat Rev Immunol. 2008 Jun;8(6):458-66 PMID: 18500230
  95. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense.
    PLoS Genet. 2009 Jul;5(7):e1000562 PMID: 19609346
  96. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large.
    Annu Rev Immunol. 2006;24:353-89 PMID: 16551253
  97. Convergent adaptation of human lactase persistence in Africa and Europe.
    Nat Genet. 2007 Jan;39(1):31-40 PMID: 17159977
  98. Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.
    Semin Immunol. 2006 Dec;18(6):347-61 PMID: 16997570
  99. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.
    Immunity. 2011 May 27;34(5):637-50 PMID: 21616434
  100. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock.
    Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10272-7 PMID: 19509334
  101. Confronting potential influenza A (H5N1) pandemic with better vaccines.
    Emerg Infect Dis. 2007 Oct;13(10):1512-8 PMID: 18258000
  102. Is mate choice in humans MHC-dependent?
    PLoS Genet. 2008 Sep 12;4(9):e1000184 PMID: 18787687
  103. An integrated encyclopedia of DNA elements in the human genome.
    Nature. 2012 Sep 6;489(7414):57-74 PMID: 22955616
  104. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.
    Nat Genet. 2001 Nov;29(3):301-5 PMID: 11687797
  105. A new vision of immunity: homeostasis of the superorganism.
    Mucosal Immunol. 2010 Sep;3(5):450-60 PMID: 20445502
  106. Personal and population genomics of human regulatory variation.
    Genome Res. 2012 Sep;22(9):1689-97 PMID: 22955981
  107. Spread of an inactive form of caspase-12 in humans is due to recent positive selection.
    Am J Hum Genet. 2006 Apr;78(4):659-70 PMID: 16532395
  108. IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans.
    Immunity. 2008 Nov 14;29(5):746-57 PMID: 19006693
  109. Interactions between the microbiota and the immune system.
    Science. 2012 Jun 8;336(6086):1268-73 PMID: 22674334
  110. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.
    Nature. 2009 Oct 8;461(7265):798-801 PMID: 19759533
  111. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection.
    Nature. 1988 Sep 8;335(6186):167-70 PMID: 3412472
  112. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.
    Cell. 2004 Jul 23;118(2):229-41 PMID: 15260992
  113. Natural selection has driven population differentiation in modern humans.
    Nat Genet. 2008 Mar;40(3):340-5 PMID: 18246066
  114. The signature of long-standing balancing selection at the human defensin beta-1 promoter.
    Genome Biol. 2008;9(9):R143 PMID: 18817538
  115. Up to new tricks - a review of cross-species transmission of influenza A viruses.
    Anim Health Res Rev. 2007 Jun;8(1):1-21 PMID: 17692139
  116. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation.
    Curr Biol. 2010 Feb 23;20(4):R208-15 PMID: 20178769
  117. Complex signatures of natural selection at the Duffy blood group locus.
    Am J Hum Genet. 2002 Feb;70(2):369-83 PMID: 11753822
  118. Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy.
    J Immunol. 2007 Jun 15;178(12):7520-4 PMID: 17548585
  119. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies.
    Am J Hum Genet. 2007 Apr;80(4):727-39 PMID: 17357078
  120. Patterns of positive selection in six Mammalian genomes.
    PLoS Genet. 2008 Aug 01;4(8):e1000144 PMID: 18670650
  121. Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.
    J Cell Biol. 2006 Oct 23;175(2):209-15 PMID: 17060494
  122. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.
    PLoS Genet. 2011 Nov;7(11):e1002355 PMID: 22072984
  123. Adaptation and constraint at Toll-like receptors in primates.
    Mol Biol Evol. 2010 Sep;27(9):2172-86 PMID: 20410160
  124. Pathogen-driven selection and worldwide HLA class I diversity.
    Curr Biol. 2005 Jun 7;15(11):1022-7 PMID: 15936272
  125. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus.
    Nature. 2007 Jan 18;445(7125):319-23 PMID: 17230189
  126. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16645-50 PMID: 17925445
  127. Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3.
    Hum Mol Genet. 2005 Jul 15;14(14):2045-52 PMID: 15944200
  128. Linking disease associations with regulatory information in the human genome.
    Genome Res. 2012 Sep;22(9):1748-59 PMID: 22955986
  129. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes.
    Genes Immun. 2009 Mar;10(2):120-4 PMID: 18946481
  130. The selective footprints of viral pressures at the human RIG-I-like receptor family.
    Hum Mol Genet. 2011 Nov 15;20(22):4462-74 PMID: 21865300
  131. Evolutionary genetic dissection of human interferons.
    J Exp Med. 2011 Dec 19;208(13):2747-59 PMID: 22162829
  132. Recognition of microorganisms and activation of the immune response.
    Nature. 2007 Oct 18;449(7164):819-26 PMID: 17943118
  133. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides.
    Eur J Immunol. 2007 Aug;37(8):2280-9 PMID: 17595679
  134. The hygiene hypothesis: an evolutionary perspective.
    Microbes Infect. 2010 Jun;12(6):421-7 PMID: 20178858
  135. Full-exon resequencing reveals toll-like receptor variants contribute to human susceptibility to tuberculosis disease.
    PLoS One. 2007 Dec 19;2(12):e1318 PMID: 18091991
  136. Pyogenic bacterial infections in humans with IRAK-4 deficiency.
    Science. 2003 Mar 28;299(5615):2076-9 PMID: 12637671
  137. Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5897-901 PMID: 2062867
  138. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages.
    Nat Immunol. 2006 Jun;7(6):576-82 PMID: 16648852
  139. The gut microbiota shapes intestinal immune responses during health and disease.
    Nat Rev Immunol. 2009 May;9(5):313-23 PMID: 19343057
  140. Immune signaling by RIG-I-like receptors.
    Immunity. 2011 May 27;34(5):680-92 PMID: 21616437
  141. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.
    Nat Genet. 2009 Oct;41(10):1105-9 PMID: 19749757
  142. Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7073-8 PMID: 19359493
  143. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity.
    Immunol Rev. 2007 Dec;220:251-69 PMID: 17979852
  144. Human genetic susceptibility to infectious disease.
    Nat Rev Genet. 2012 Feb 07;13(3):175-88 PMID: 22310894
  145. The evolutionary landscape of cytosolic microbial sensors in humans.
    Am J Hum Genet. 2012 Jul 13;91(1):27-37 PMID: 22748209
  146. Darwinian and demographic forces affecting human protein coding genes.
    Genome Res. 2009 May;19(5):838-49 PMID: 19279335
  147. Balancing selection and its effects on sequences in nearby genome regions.
    PLoS Genet. 2006 Apr;2(4):e64 PMID: 16683038
  148. Defensins in innate antiviral immunity.
    Nat Rev Immunol. 2006 Jun;6(6):447-56 PMID: 16724099
  149. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes.
    Science. 2009 Apr 17;324(5925):387-9 PMID: 19264985
  150. Gene conversion and evolution of gene families: an overview.
    Genes (Basel). 2010 Sep 30;1(3):349-56 PMID: 24710091
  151. Patterns of evolution and host gene mimicry in influenza and other RNA viruses.
    PLoS Pathog. 2008 Jun 06;4(6):e1000079 PMID: 18535658
  152. Recent and ongoing selection in the human genome.
    Nat Rev Genet. 2007 Nov;8(11):857-68 PMID: 17943193
  153. TLR3 deficiency in patients with herpes simplex encephalitis.
    Science. 2007 Sep 14;317(5844):1522-7 PMID: 17872438
  154. A scan for positively selected genes in the genomes of humans and chimpanzees.
    PLoS Biol. 2005 Jun;3(6):e170 PMID: 15869325
  155. Human Mannose-binding Lectin in Immunity: Friend, Foe, or Both?
    J Exp Med. 2004 May 17;199(10):1295-9 PMID: 15148331
  156. Mannose-binding lectin and its genetic variants.
    Genes Immun. 2006 Mar;7(2):85-94 PMID: 16395391
  157. Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
    Science. 2003 Dec 12;302(5652):1960-3 PMID: 14671302
  158. Mannan-binding lectin enhances susceptibility to visceral leishmaniasis.
    Infect Immun. 2001 Aug;69(8):5212-5 PMID: 11447210
Article Info
Journal
Nature reviews. Immunology
Abbr.
Nat Rev Immunol
ISSN
1474-1741
DOI
10.1038/nri3421
Email
[email protected]
Published
2013-04-00
Epub
2013-00-08
Pages
280-93
Language
English
Region
England
NLM ID
101124169
PMCID
PMC4015519
Subset
IM
Grants
NIAID NIH HHS · R01 AI064950 · United States
External Links
PubMed source DOI: 10.1038/nri3421 PMC Full Text View journal details
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