From evolutionary genetics to human immunology: how selection shapes host defence genes (original) (raw)
Casanova, J. L. & Abel, L. Inborn errors of immunity to infection: the rule rather than the exception. J. Exp. Med.202, 197–201 (2005). CASPubMedPubMed Central Google Scholar
Haldane, J. B. S. Disease and evolution. Ric. Sci.19 (Suppl. A), 68–76 (1949). Google Scholar
Ausubel, F. M. Are innate immune signaling pathways in plants and animals conserved? Nature Immunol.6, 973–979 (2005). CAS Google Scholar
Cooper, M. D. & Alder, M. N. The evolution of adaptive immune systems. Cell124, 815–822 (2006). CASPubMed Google Scholar
Flajnik, M. F. & Du Pasquier, L. Evolution of innate and adaptive immunity: can we draw a line? Trends Immunol.25, 640–644 (2004). CASPubMed Google Scholar
Kimbrell, D. A. & Beutler, B. The evolution and genetics of innate immunity. Nature Rev. Genet.2, 256–267 (2001). CASPubMed Google Scholar
Lazzaro, B. P. & Little, T. J. Immunity in a variable world. Phil. Trans. R. Soc. Lond. B364, 15–26 (2009). Google Scholar
Schulenburg, H., Kurtz, J., Moret, Y. & Siva-Jothy, M. T. Introduction. Ecological immunology. Phil. Trans. R. Soc. Lond. B364, 3–14 (2009). Google Scholar
Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell124, 783–801 (2006). CASPubMed Google Scholar
Medzhitov, R. Recognition of microorganisms and activation of the immune response. Nature449, 819–826 (2007). An integrated view of the innate and adaptive components of the immune system, how they work and interact, and their role in host defence. CASPubMed Google Scholar
Allison, A. C. Protection afforded by sickle-cell trait against subtertian malareal infection. BMJ1, 290–294 (1954). The seminal paper that showed that 'sickle-cell' heterozygotes have increased protection against malaria. CASPubMedPubMed Central Google Scholar
Nielsen, R., Hellmann, I., Hubisz, M., Bustamante, C. & Clark, A. G. Recent and ongoing selection in the human genome. Nature Rev. Genet.8, 857–868 (2007). CASPubMed Google Scholar
Sabeti, P. C. et al. Positive natural selection in the human lineage. Science312, 1614–1620 (2006). ArticleCASPubMed Google Scholar
Akey, J. M. Constructing genomic maps of positive selection in humans: where do we go from here? Genome Res.19, 711–722 (2009). References 12–14 are excellent reviews on how recent positive selection has targeted the human genome. They discuss the major findings of genome-wide scans for selection and their strengths and weaknesses. CASPubMedPubMed Central Google Scholar
Trowsdale, J. & Parham, P. Mini-review: defense strategies and immunity-related genes. Eur. J. Immunol.34, 7–17 (2004). CASPubMed Google Scholar
Varki, A. A chimpanzee genome project is a biomedical imperative. Genome Res.10, 1065–1070 (2000). CASPubMed Google Scholar
Varki, A. & Altheide, T. K. Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res.15, 1746–1758 (2005). CASPubMed Google Scholar
Yang, Z. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol. Biol. Evol.15, 568–573 (1998). CASPubMed Google Scholar
Arbiza, L., Dopazo, J. & Dopazo, H. Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome. PLoS Comput. Biol.2, e38 (2006). PubMedPubMed Central Google Scholar
Bustamante, C. D. et al. Natural selection on protein-coding genes in the human genome. Nature437, 1153–1157 (2005). This paper assesses the genome-wide impact of weak negative and positive selection on protein-coding regions since humans and chimpanzees started to diverge. CASPubMed Google Scholar
The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature437, 69–87 (2005).
Gibbs, R. A. et al. Evolutionary and biomedical insights from the rhesus macaque genome. Science316, 222–234 (2007). CASPubMed Google Scholar
Nielsen, R. et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol.3, e170 (2005). PubMedPubMed Central Google Scholar
Kosiol, C. et al. Patterns of positive selection in six mammalian genomes. PLoS Genet.4, e1000144 (2008). PubMedPubMed Central Google Scholar
International Chicken Genome Sequencing Consortium. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature432, 695–716 (2004).
Clark, A. G. et al. Inferring nonneutral evolution from human–chimp–mouse orthologous gene trios. Science302, 1960–1963 (2003). The first genome-wide analysis of genes evolving under positive selection in the human evolutionary lineage. CASPubMed Google Scholar
Bakewell, M. A., Shi, P. & Zhang, J. More genes underwent positive selection in chimpanzee evolution than in human evolution. Proc. Natl Acad. Sci. USA104, 7489–7494 (2007). CASPubMedPubMed Central Google Scholar
Vamathevan, J. J. et al. The role of positive selection in determining the molecular cause of species differences in disease. BMC Evol. Biol.8, 273 (2008). PubMedPubMed Central Google Scholar
Sharp, P. M., Shaw, G. M. & Hahn, B. H. Simian immunodeficiency virus infection of chimpanzees. J. Virol.79, 3891–3902 (2005). CASPubMedPubMed Central Google Scholar
Silvestri, G. Immunity in natural SIV infections. J. Intern. Med.265, 97–109 (2009). CASPubMed Google Scholar
Keele, B. F. et al. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature460, 515–519 (2009). CASPubMedPubMed Central Google Scholar
Seeler, J. S., Muchardt, C., Suessle, A. & Gaynor, R. B. Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene expression. J. Virol.68, 1002–1009 (1994). CASPubMedPubMed Central Google Scholar
Gonzalez, E. et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science307, 1434–1440 (2005). CASPubMed Google Scholar
Degenhardt, J. D. et al. Copy number variation of _CCL3_-like genes affects rate of progression to simian-AIDS in rhesus macaques (Macaca mulatta). PLoS Genet.5, e1000346 (2009). PubMedPubMed Central Google Scholar
Baum, J., Ward, R. H. & Conway, D. J. Natural selection on the erythrocyte surface. Mol. Biol. Evol.19, 223–229 (2002). CASPubMed Google Scholar
Wang, H. Y., Tang, H., Shen, C. K. & Wu, C. I. Rapidly evolving genes in human. I. The glycophorins and their possible role in evading malaria parasites. Mol. Biol. Evol.20, 1795–1804 (2003). CASPubMed Google Scholar
Wilder, J. A., Hewett, E. K. & Gansner, M. E. Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans. Mol. Biol. Evol. 13 Aug 2009 (doi:10.1093/molbev/msp183). CASPubMedPubMed Central Google Scholar
Maier, A. G. et al. Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nature Med.9, 87–92 (2003). CASPubMed Google Scholar
Sim, B. K., Chitnis, C. E., Wasniowska, K., Hadley, T. J. & Miller, L. H. Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science264, 1941–1944 (1994). CASPubMed Google Scholar
Martin, M. J., Rayner, J. C., Gagneux, P., Barnwell, J. W. & Varki, A. Evolution of human–chimpanzee differences in malaria susceptibility: relationship to human genetic loss of _N_-glycolylneuraminic acid. Proc. Natl Acad. Sci. USA102, 12819–12824 (2005). CASPubMedPubMed Central Google Scholar
King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science188, 107–116 (1975). CASPubMed Google Scholar
Blekhman, R., Oshlack, A., Chabot, A. E., Smyth, G. K. & Gilad, Y. Gene regulation in primates evolves under tissue-specific selection pressures. PLoS Genet.4, e1000271 (2008). PubMedPubMed Central Google Scholar
Hahn, M. W., Demuth, J. P. & Han, S. G. Accelerated rate of gene gain and loss in primates. Genetics177, 1941–1949 (2007). PubMedPubMed Central Google Scholar
Dumas, L. et al. Gene copy number variation spanning 60 million years of human and primate evolution. Genome Res.17, 1266–1277 (2007). CASPubMedPubMed Central Google Scholar
Carlson, C. S. et al. Genomic regions exhibiting positive selection identified from dense genotype data. Genome Res.15, 1553–1565 (2005). CASPubMedPubMed Central Google Scholar
Kelley, J. L., Madeoy, J., Calhoun, J. C., Swanson, W. & Akey, J. M. Genomic signatures of positive selection in humans and the limits of outlier approaches. Genome Res.16, 980–989 (2006). CASPubMedPubMed Central Google Scholar
Williamson, S. H. et al. Localizing recent adaptive evolution in the human genome. PLoS Genet.3, e90 (2007). PubMedPubMed Central Google Scholar
Barreiro, L. B., Laval, G., Quach, H., Patin, E. & Quintana-Murci, L. Natural selection has driven population differentiation in modern humans. Nature Genet.40, 340–345 (2008). CASPubMed Google Scholar
Kimura, R., Fujimoto, A., Tokunaga, K. & Ohashi, J. A practical genome scan for population-specific strong selective sweeps that have reached fixation. PLoS ONE2, e286 (2007). PubMedPubMed Central Google Scholar
Sabeti, P. C. et al. Genome-wide detection and characterization of positive selection in human populations. Nature449, 913–918 (2007). CASPubMedPubMed Central Google Scholar
Tang, K., Thornton, K. R. & Stoneking, M. A new approach for using genome scans to detect recent positive selection in the human genome. PLoS Biol.5, e171 (2007). PubMedPubMed Central Google Scholar
Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. A map of recent positive selection in the human genome. PLoS Biol.4, e72 (2006). This paper reports a genome-wide scan, based on haplotype structure information, for recent and ongoing positive selection in human populations. ArticlePubMedPubMed Central Google Scholar
Wang, E. T., Kodama, G., Baldi, P. & Moyzis, R. K. Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc. Natl Acad. Sci. USA103, 135–140 (2006). CASPubMed Google Scholar
Wolfe, N. D., Dunavan, C. P. & Diamond, J. Origins of major human infectious diseases. Nature447, 279–283 (2007). CASPubMedPubMed Central Google Scholar
Anderson, R. M. & May, R. M. Infectious Diseases of Humans: Dynamics and Control (Oxford Univ. Press, 1991). Google Scholar
Fumagalli, M. et al. Widespread balancing selection and pathogen-driven selection at blood group antigen genes. Genome Res.19, 199–212 (2009). CASPubMedPubMed Central Google Scholar
Fumagalli, M. et al. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J. Exp. Med.206, 1395–1408 (2009). CASPubMedPubMed Central Google Scholar
Prugnolle, F. et al. Pathogen-driven selection and worldwide HLA class I diversity. Curr. Biol.15, 1022–1027 (2005). The first study to correlate the worldwide genetic diversity at HLA class I genes with pathogen presence. CASPubMed Google Scholar
Hughes, A. L. & Nei, M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature335, 167–170 (1988). CASPubMed Google Scholar
Hedrick, P. W., Whittam, T. S. & Parham, P. Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes. Proc. Natl Acad. Sci. USA88, 5897–5901 (1991). CASPubMedPubMed Central Google Scholar
Takahata, N., Satta, Y. & Klein, J. Polymorphism and balancing selection at major histocompatibility complex loci. Genetics130, 925–938 (1992). References 60–62 describe how the extraordinary levels of genetic diversity observed at the major histocompatibility complex may result from the action of balancing selection. CASPubMedPubMed Central Google Scholar
Bamshad, M. J. et al. A strong signature of balancing selection in the 5′ _cis_-regulatory region of CCR5. Proc. Natl Acad. Sci. USA99, 10539–10544 (2002). CASPubMedPubMed Central Google Scholar
Novembre, J., Galvani, A. P. & Slatkin, M. The geographic spread of the CCR5 Δ_32_ HIV-resistance allele. PLoS Biol.3, e339 (2005). PubMedPubMed Central Google Scholar
Stephens, J. C. et al. Dating the origin of the CCR5_-Δ_32 AIDS-resistance allele by the coalescence of haplotypes. Am. J. Hum. Genet.62, 1507–1515 (1998). CASPubMedPubMed Central Google Scholar
Arenzana-Seisdedos, F. & Parmentier, M. Genetics of resistance to HIV infection: role of co-receptors and co-receptor ligands. Semin. Immunol.18, 387–403 (2006). CASPubMed Google Scholar
Gonzalez, E. et al. Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proc. Natl Acad. Sci. USA96, 12004–12009 (1999). CASPubMedPubMed Central Google Scholar
Lalani, A. S. et al. Use of chemokine receptors by poxviruses. Science286, 1968–1971 (1999). CASPubMed Google Scholar
Single, R. M. et al. Global diversity and evidence for coevolution of KIR and HLA. Nature Genet.39, 1114–1119 (2007). CASPubMed Google Scholar
Chaix, R., Cao, C. & Donnelly, P. Is mate choice in humans MHC-dependent? PLoS Genet.4, e1000184 (2008). PubMedPubMed Central Google Scholar
Parham, P. & Ohta, T. Population biology of antigen presentation by MHC class I molecules. Science272, 67–74 (1996). CASPubMed Google Scholar
Snow, R. W., Guerra, C. A., Noor, A. M., Myint, H. Y. & Hay, S. I. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature434, 214–217 (2005). CASPubMedPubMed Central Google Scholar
Kwiatkowski, D. P. How malaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet.77, 171–192 (2005). The most comprehensive review of the genetic basis of resistance to malaria in humans and the selective pressures that are exerted by malaria in the human genome. CASPubMedPubMed Central Google Scholar
Flint, J., Harding, R. M., Boyce, A. J. & Clegg, J. B. The population genetics of the haemoglobinopathies. Baillieres Clin. Haematol.11, 1–51 (1998). CASPubMed Google Scholar
Agarwal, A. et al. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood96, 2358–2363 (2000). CASPubMed Google Scholar
Modiano, D. et al. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature414, 305–308 (2001). CASPubMed Google Scholar
Chotivanich, K. et al. Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P. falciparum malaria. Blood100, 1172–1176 (2002). CASPubMed Google Scholar
Ohashi, J. et al. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am. J. Hum. Genet.74, 1198–1208 (2004). CASPubMedPubMed Central Google Scholar
Chitnis, C. E. & Miller, L. H. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J. Exp. Med.180, 497–506 (1994). CASPubMed Google Scholar
Tournamille, C., Colin, Y., Cartron, J. P. & Le Van Kim, C. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nature Genet.10, 224–228 (1995). CASPubMed Google Scholar
Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. The History and Geography of Human Genes (Princeton Univ. Press, 1994). Google Scholar
Hamblin, M. T. & Di Rienzo, A. Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. Am. J. Hum. Genet.66, 1669–1679 (2000). CASPubMedPubMed Central Google Scholar
Hamblin, M. T., Thompson, E. E. & Di Rienzo, A. Complex signatures of natural selection at the Duffy blood group locus. Am. J. Hum. Genet.70, 369–383 (2002). PubMed Google Scholar
Aitman, T. J. et al. Malaria susceptibility and CD36 mutation. Nature405, 1015–1016 (2000). CASPubMed Google Scholar
Ruwende, C. & Hill, A. Glucose-6-phosphate dehydrogenase deficiency and malaria. J. Mol. Med.76, 581–588 (1998). CASPubMed Google Scholar
Sabeti, P. et al. CD40L association with protection from severe malaria. Genes Immun.3, 286–291 (2002). CASPubMed Google Scholar
The International HapMap Consortium. A haplotype map of the human genome. Nature437, 1299–1320 (2005).
Sabeti, P. C. et al. Detecting recent positive selection in the human genome from haplotype structure. Nature419, 832–837 (2002). CASPubMed Google Scholar
Currat, M. et al. Molecular analysis of the β-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the βS Senegal mutation. Am. J. Hum. Genet.70, 207–223 (2002). CASPubMed Google Scholar
Saunders, M. A., Hammer, M. F. & Nachman, M. W. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics162, 1849–1861 (2002). CASPubMedPubMed Central Google Scholar
Tishkoff, S. A. et al. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science293, 455–462 (2001). CASPubMed Google Scholar
Joy, D. A. et al. Early origin and recent expansion of Plasmodium falciparum. Science300, 318–321 (2003). CASPubMed Google Scholar
Coluzzi, M., Sabatini, A., della Torre, A., Di Deco, M. A. & Petrarca, V. A polytene chromosome analysis of the Anopheles gambiae species complex. Science298, 1415–1418 (2002). CASPubMed Google Scholar
Barreiro, L. B. et al. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet.5, e1000562 (2009). The first evolutionary dissection of how natural selection has targeted theTLRfamily members in humans. PubMedPubMed Central Google Scholar
Dobson, A. in The Cambridge Encyclopedia of Human Evolution (eds Jones, S., Martin, R. & Pilbeam, D.) 411–420 (Cambridge Univ. Press, 1992). Google Scholar
Quintana-Murci, L., Alcais, A., Abel, L. & Casanova, J. L. Immunology in natura: clinical, epidemiological and evolutionary genetics of infectious diseases. Nature Immunol.8, 1165–1171 (2007). CAS Google Scholar
Garred, P., Larsen, F., Seyfarth, J., Fujita, R. & Madsen, H. O. Mannose-binding lectin and its genetic variants. Genes Immun.7, 85–94 (2006). CASPubMed Google Scholar
Casanova, J. L. & Abel, L. Human mannose-binding lectin in immunity: friend, foe, or both? J. Exp. Med.199, 1295–1299 (2004). CASPubMedPubMed Central Google Scholar
Eisen, D. P. & Minchinton, R. M. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin. Infect. Dis.37, 1496–1505 (2003). CASPubMed Google Scholar
Verdu, P. et al. Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles. Hum. Mol. Genet.15, 2650–2658 (2006). CASPubMed Google Scholar
Bernig, T. et al. Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection. Genes Immun.5, 461–476 (2004). CASPubMed Google Scholar
Mukherjee, S., Sarkar-Roy, N., Wagener, D. K. & Majumder, P. P. Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature. Proc. Natl Acad. Sci. USA106, 7073–7078 (2009). PubMedPubMed Central Google Scholar
Walsh, E. C. et al. Searching for signals of evolutionary selection in 168 genes related to immune function. Hum. Genet.119, 92–102 (2006). CASPubMed Google Scholar
Lynch, N. J. et al. L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement. J. Immunol.172, 1198–1202 (2004). CASPubMed Google Scholar
Roos, A. et al. Antibody-mediated activation of the classical pathway of complement may compensate for mannose-binding lectin deficiency. Eur. J. Immunol.34, 2589–2598 (2004). CASPubMed Google Scholar
Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature410, 1099–1103 (2001). CASPubMed Google Scholar
Hawn, T. R. et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J. Exp. Med.198, 1563–1572 (2003). CASPubMedPubMed Central Google Scholar
Wlasiuk, G., Khan, S., Switzer, W. M. & Nachman, M. W. A history of recurrent positive selection at the Toll-like receptor 5 in primates. Mol. Biol. Evol.26, 937–949 (2009). CASPubMedPubMed Central Google Scholar
Hawn, T. R. et al. A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus. Proc. Natl Acad. Sci. USA102, 10593–10597 (2005). CASPubMedPubMed Central Google Scholar
Franchi, L. et al. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nature Immunol.7, 576–582 (2006). CAS Google Scholar
Miao, E. A., Andersen-Nissen, E., Warren, S. E. & Aderem, A. TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin. Immunopathol.29, 275–288 (2007). CASPubMed Google Scholar
Olson, M. V. When less is more: gene loss as an engine of evolutionary change. Am. J. Hum. Genet.64, 18–23 (1999). CASPubMedPubMed Central Google Scholar
Hirayasu, K. et al. Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians. Am. J. Hum. Genet.82, 1075–1083 (2008). CASPubMedPubMed Central Google Scholar
Seixas, S. et al. Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2. Mol. Biol. Evol.24, 587–598 (2007). CASPubMed Google Scholar
Xue, Y. et al. Spread of an inactive form of caspase-12 in humans is due to recent positive selection. Am. J. Hum. Genet.78, 659–670 (2006). An intriguing example of how the loss of an immunity-related gene can represent a selective advantage in humans. CASPubMedPubMed Central Google Scholar
Yngvadottir, B. et al. A genome-wide survey of the prevalence and evolutionary forces acting on human nonsense SNPs. Am. J. Hum. Genet.84, 224–234 (2009). CASPubMedPubMed Central Google Scholar
Saleh, M. et al. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature429, 75–79 (2004). CASPubMed Google Scholar
Scott, A. M. & Saleh, M. The inflammatory caspases: guardians against infections and sepsis. Cell Death Differ.14, 23–31 (2007). CASPubMed Google Scholar
Perry, G. H. et al. Copy number variation and evolution in humans and chimpanzees. Genome Res.18, 1698–1710 (2008). CASPubMedPubMed Central Google Scholar
Blekhman, R. et al. Natural selection on genes that underlie human disease susceptibility. Curr. Biol.18, 883–889 (2008). CASPubMedPubMed Central Google Scholar
Nielsen, R. et al. Darwinian and demographic forces affecting human protein coding genes. Genome Res.19, 838–849 (2009). CASPubMedPubMed Central Google Scholar
Picard, C. et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science299, 2076–2079 (2003). CASPubMed Google Scholar
von Bernuth, H. et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science321, 691–696 (2008). CASPubMedPubMed Central Google Scholar
Zhang, S. Y. et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science317, 1522–1527 (2007). CASPubMed Google Scholar
Casanova, J. L. & Abel, L. Human genetics of infectious diseases: a unified theory. EMBO J.26, 915–922 (2007). An important review of the genetic basis of infectious diseases in humans, bridging the dysfunctional gap between Mendelian genetics and population-based complex genetics. CASPubMedPubMed Central Google Scholar
Di Rienzo, A. Population genetics models of common diseases. Curr. Opin. Genet. Dev.16, 630–636 (2006). CASPubMed Google Scholar
Smirnova, I., Hamblin, M. T., McBride, C., Beutler, B. & Di Rienzo, A. Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans. Genetics158, 1657–1664 (2001). CASPubMedPubMed Central Google Scholar
Schroder, N. W. & Schumann, R. R. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect. Dis.5, 156–164 (2005). PubMed Google Scholar
Ma, X. et al. Full-exon resequencing reveals Toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS ONE2, e1318 (2007). PubMedPubMed Central Google Scholar
Misch, E. A. et al. Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction. PLoS Negl. Trop. Dis.2, e231 (2008). PubMedPubMed Central Google Scholar
Pickrell, J. K. et al. Signals of recent positive selection in a worldwide sample of human populations. Genome Res.19, 826–837 (2009). CASPubMedPubMed Central Google Scholar
Gilad, Y., Rifkin, S. A. & Pritchard, J. K. Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet.24, 408–415 (2008). CASPubMedPubMed Central Google Scholar
Dimas, A. S. et al. Modifier effects between regulatory and protein-coding variation. PLoS Genet.4, e1000244 (2008). PubMedPubMed Central Google Scholar
Stranger, B. E. et al. Population genomics of human gene expression. Nature Genet.39, 1217–1224 (2007). CASPubMed Google Scholar
Kudaravalli, S., Veyrieras, J. B., Stranger, B. E., Dermitzakis, E. T. & Pritchard, J. K. Gene expression levels are a target of recent natural selection in the human genome. Mol. Biol. Evol.26, 649–658 (2009). CASPubMed Google Scholar
Dimas, A. S. et al. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science325, 1246–1250 (2009). CASPubMedPubMed Central Google Scholar
Ko, D. C. et al. A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease. Am. J. Hum. Genet.85, 214–227 (2009). CASPubMedPubMed Central Google Scholar
Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol.20, 197–216 (2002). CASPubMed Google Scholar
Beutler, B. et al. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu. Rev. Immunol.24, 353–389 (2006). CASPubMed Google Scholar
Medzhitov, R. Toll-like receptors and innate immunity. Nature Rev. Immunol.1, 135–145 (2001). CAS Google Scholar
Leulier, F. & Lemaitre, B. Toll-like receptors — taking an evolutionary approach. Nature Rev. Genet.9, 165–178 (2008). An outstanding overview of the origins, evolution and different functions of TLRs across the animal kingdom. CASPubMed Google Scholar
Kawai, T. & Akira, S. Innate immune recognition of viral infection. Nature Immunol.7, 131–137 (2006). CAS Google Scholar
Geijtenbeek, T. B., van Vliet, S. J., Engering, A., ' t Hart, B. A. & van Kooyk, Y. Self- and nonself-recognition by C-type lectins on dendritic cells. Annu. Rev. Immunol.22, 33–54 (2004). CASPubMed Google Scholar
Fritz, J. H., Ferrero, R. L., Philpott, D. J. & Girardin, S. E. Nod-like proteins in immunity, inflammation and disease. Nature Immunol.7, 1250–1257 (2006). CAS Google Scholar
Takeuchi, O. & Akira, S. Recognition of viruses by innate immunity. Immunol. Rev.220, 214–224 (2007). CASPubMed Google Scholar
Schatz, D. G., Oettinger, M. A. & Schlissel, M. S. V(D)J recombination: molecular biology and regulation. Annu. Rev. Immunol.10, 359–383 (1992). CASPubMed Google Scholar
Bendelac, A., Bonneville, M. & Kearney, J. F. Autoreactivity by design: innate B and T lymphocytes. Nature Rev. Immunol.1, 177–186 (2001). CAS Google Scholar
Klein, J. Natural History of the Major Histocompatibility Complex (Wiley, New York, 1986). Google Scholar
McDevitt, H. O. Discovering the role of the major histocompatibility complex in the immune response. Annu. Rev. Immunol.18, 1–17 (2000). CASPubMed Google Scholar
Hurst, L. D. Genetics and the understanding of selection. Nature Rev. Genet.10, 83–93 (2009). CASPubMed Google Scholar
Nielsen, R. Molecular signatures of natural selection. Annu. Rev. Genet.39, 197–218 (2005). CASPubMed Google Scholar
Kreitman, M. Methods to detect selection in populations with applications to the human. Annu. Rev. Genomics Hum. Genet.1, 539–559 (2000). References 152–154 are thorough reviews on how natural selection acts, its signatures and implications, and the different methods used for detecting selection based on population genetic data. CASPubMed Google Scholar
Eyre-Walker, A. & Keightley, P. D. High genomic deleterious mutation rates in hominids. Nature397, 344–347 (1999). CASPubMed Google Scholar
Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet.80, 727–739 (2007). CASPubMedPubMed Central Google Scholar
Przeworski, M., Coop, G. & Wall, J. D. The signature of positive selection on standing genetic variation. Evolution59, 2312–2323 (2005). PubMed Google Scholar
Charlesworth, D. Balancing selection and its effects on sequences in nearby genome regions. PLoS Genet.2, e64 (2006). PubMedPubMed Central Google Scholar
McDonald, J. H. & Kreitman, M. Adaptive protein evolution at the Adh locus in Drosophila. Nature351, 652–654 (1991). CASPubMed Google Scholar
Nielsen, R. & Yang, Z. Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics148, 929–936 (1998). CASPubMedPubMed Central Google Scholar
Yang, Z. & Bielawski, J. P. Statistical methods for detecting molecular adaptation. Trends Ecol. Evol.15, 496–503 (2000). CASPubMedPubMed Central Google Scholar
Guindon, S., Black, M. & Rodrigo, A. Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Control of the false discovery rate applied to the detection of positively selected amino acid sites. Mol. Biol. Evol.23, 919–926 (2006). CASPubMed Google Scholar
Thornton, K. R., Jensen, J. D., Becquet, C. & Andolfatto, P. Progress and prospects in mapping recent selection in the genome. Heredity98, 340–348 (2007). CASPubMed Google Scholar
Weir, C. L. & Cockerham, C. C. Estimating F-statistics for the analysis of population structure. Evolution38, 1358–1370 (1984). CASPubMed Google Scholar
Hartl, D. L. & Clark, A. G. Principles of Population Genetics (Sinauer Associates Inc., Sunderland, 2007). Google Scholar
Phillips, P. C. Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems. Nature Rev. Genet.9, 855–867 (2008). CASPubMed Google Scholar
Vilches, C. & Parham, P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu. Rev. Immunol.20, 217–251 (2002). CASPubMed Google Scholar
Rajagopalan, S. & Long, E. O. Understanding how combinations of HLA and KIR genes influence disease. J. Exp. Med.201, 1025–1029 (2005). CASPubMedPubMed Central Google Scholar
Norman, P. J. et al. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nature Genet.39, 1092–1099 (2007). CASPubMed Google Scholar