Evidence for polygenic adaptation to pathogens in the human genome

Molecular Biology and Evolution

Volumn 30, Issue 7, 2013, Pages 1544-1558

  Daub, Josephine T ^a,b   Hofer, Tamara ^a,b   Cutivet, Emilie ^a   Dupanloup, Isabelle ^a,b   Quintana Murci, Lluis ^c,d   Robinson Rechavi, Marc ^b,e   Excoffier, Laurent ^a,b  

^a UNIVERSITY OF BERN   (Switzerland)

^b SWISS INSTITUTE OF BIOINFORMATICS   (Switzerland)

^c INSTITUT PASTEUR   (France)

^d CNRS   (France)

^e UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

adaptation; epistasis; human evolution; pathway analysis; polygenic selection

Indexed keywords

BONE MORPHOGENETIC PROTEIN; CYTOKINE; FATTY ACID; MESSENGER RNA;

AMINO ACID METABOLISM; ARTICLE; BACTERIAL IMMUNITY; CELL MEMBRANE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOSKELETON; EVOLUTIONARY ADAPTATION; FATTY ACID OXIDATION; GENE INTERACTION; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENE SET; GENETIC ASSOCIATION; GENETIC SELECTION; GENOME; GENOTYPING TECHNIQUE; HUMAN; HUMAN CELL; HUMAN GENOME; IMMUNE RESPONSE; LIPID METABOLISM; MULTIFACTORIAL INHERITANCE; POLYGENIC ADAPTATION; SIGNAL TRANSDUCTION; VISION;

ADAPTATION; EPISTASIS; HUMAN EVOLUTION; PATHWAY ANALYSIS; POLYGENIC SELECTION;

ADAPTATION, BIOLOGICAL; EPISTASIS, GENETIC; GENOME, HUMAN; GENOTYPE; HOST-PATHOGEN INTERACTIONS; HUMANS; LINKAGE DISEQUILIBRIUM; METABOLIC NETWORKS AND PATHWAYS; MODELS, THEORETICAL; MULTIFACTORIAL INHERITANCE; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; SELECTION, GENETIC;

EID: 84879353196     PISSN: 07374038     EISSN: 15371719     Source Type: Journal    
DOI: 10.1093/molbev/mst080     Document Type: Article

References (121)

1. Ackermann M, Strimmer K. 2009. A general modular framework for gene set enrichment analysis. BMC Bioinformatics 10:47.
2. Akey JM. 2009. Constructing genomic maps of positive selection in humans: where do we go from here? Genome Res. 19:711-722.
3. Alexa A, Rahnenfuhrer J, Lengauer T. 2006. Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 22:1600-1607. (Pubitemid 43985293)
4. Al-Shahrour F, Diaz-Uriarte R, Dopazo J. 2004. FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes. Bioinformatics 20:578-580. (Pubitemid 38344339)
5. Alves I, Sramkova Hanulova A, Foll M, Excoffier L. 2012. Genomic data reveal a complex making of humans. PLoS Genet. 8:e1002837.
6. Amato R, Pinelli M, Monticelli A, Marino D, Miele G, Cocozza S. 2009. Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases. PLoS One 4:e7927.
7. Anstee DJ. 2010. The relationship between blood groups and disease. Blood 115:4635-4643.
8. Armitage AE, Eddowes LA, Gileadi U, Cole S, Spottiswoode N, Selvakumar TA, Ho LP, Townsend AR, Drakesmith H. 2011. Hepcidin regulation by innate immune and infectious stimuli. Blood 118:4129-4139.
9. Balaresque PL, Ballereau SJ, Jobling MA. 2007. Challenges in human genetic diversity: demographic history and adaptation. Hum Mol Genet. 16(Spec No. 2):R134-R139.
10. Baranzini SE, Galwey NW, Wang J, et al. (15 co-authors). 2009. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum Mol Genet. 18:2078-2090.
11. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. 2008. Natural selection has driven population differentiation in modern humans. Nat Genet. 40:340-345. (Pubitemid 351311765)
12. Barreiro LB, Quintana-Murci L. 2010. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet. 11:17-30.
13. Beaumont MA. 2005. Adaptation and speciation: what can F-st tell us? Trends Ecol Evol. 20:435-440. (Pubitemid 41026729)
14. Beaumont MA, Nichols RA. 1996. Evaluating loci for use in the genetic analysis of population structure. Proc R Soc Lond B. 263: 1619-1626. (Pubitemid 27055553)
15. Besag J, Clifford P. 1991. Sequential Monte-Carlo P-values. Biometrika 78: 301-304.
16. Bi S, Baum LG. 2009. Sialic acids in T cell development and function. Biochim Biophys Acta 1790:1599-1610.
17. Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP. 2005. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl). 83:876-886. (Pubitemid 41598688)
18. Bokoch GM. 2005. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 15:163-171. (Pubitemid 40332539)
19. Boulland ML, Marquet J, Molinier-Frenkel V, et al. (11 co-authors). 2007. Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation. Blood 110:220-227. (Pubitemid 47026838)
20. Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A. 2011. Bone morphogenetic proteins: a critical review. Cell Signal. 23: 609-620.
21. Cann HM, de Toma C, Cazes L, et al. (41 co-authors). 2002. A human genome diversity cell line panel. Science 296:261-262. (Pubitemid 34303653)
22. Charlesworth B. 2012. The effects of deleterious mutations on evolution at linked sites. Genetics 190:5-22.
23. Clark JD, Beyene Y, WoldeGabriel G, et al. (13 co-authors). 2003. Stratigraphic, chronological and behavioural contexts of Pleistocene Homo sapiens from Middle Awash, Ethiopia. Nature 423:747-752. (Pubitemid 36735696)
24. Cossart P, Sansonetti PJ. 2004. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304:242-248. (Pubitemid 38452169)
25. Criss AK, Ahlgren DM, Jou TS, McCormick BA, Casanova JE. 2001. The GTPase Rac1 selectively regulates Salmonella invasion at the apical plasma membrane of polarized epithelial cells. J Cell Sci. 114: 1331-1341. (Pubitemid 32409469)
26. Dabydeen SA, Meneses PI. 2011. Smurf2 alters BPV1 trafficking and decreases infection. Arch Virol. 156:827-838.
27. Dinu I, Potter JD, Mueller T, Liu Q, Adewale AJ, Jhangri GS, Einecke G, Famulski KS, Halloran P, Yasui Y. 2007. Improving gene set analysis of microarray data by SAM-GS. BMC Bioinformatics 8:242.
28. Efron B, Tibshirani R. 2007. On testing the significance of sets of genes. Ann Appl Statist. 1:107-129.
29. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I. 2002. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 30:233-237.
30. Excoffier L, Foll M, Petit RJ. 2009. Genetic consequences of range expansions. Annu Rev Ecol Evol Syst. 40:481-501.
31. Excoffier L, Hofer T, Foll M. 2009. Detecting loci under selection in a hierarchically structured population. Heredity 103:285-298.
32. Excoffier L, Lischer HE. 2010. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour. 10:564-567.
33. Fischer KD, Kong YY, Nishina H, et al. (15 co-authors). 1998. Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr Biol. 8:554-562. (Pubitemid 28222889)
34. Fumagalli M, Fracassetti M, Cagliani R, Forni D, Pozzoli U, Comi GP, Marini F, Bresolin N, Clerici M, Sironi M. 2012. An evolutionary history of the selectin gene cluster in humans. Heredity 109:117-126.
35. Fumagalli M, Sironi M, Pozzoli U, Ferrer-Admetlla A, Pattini L, Nielsen R. 2011. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet. 7:e1002355.
36. Geer LY, Marchler-Bauer A, Geer RC, Han L, He J, He S, Liu C, Shi W, Bryant SH. 2010. The NCBI BioSystems database. Nucleic Acids Res. 38:D492-D496.
37. George RD, McVicker G, Diederich R, Ng SB, MacKenzie AP, Swanson WJ, Shendure J, Thomas JH. 2011. Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection. Genome Res. 21:1686-1694.
38. Hancock AM, Alkorta-Aranburu G, Witonsky DB, Di Rienzo A. 2010. Adaptations to new environments in humans: the role of subtle allele frequency shifts. Philos Trans R Soc Lond B Biol Sci. 365: 2459-2468.
39. Hancock AM, Witonsky DB, Alkorta-Aranburu G, Beall CM, Gebremedhin A, Sukernik R, Utermann G, Pritchard JK, Coop G, Di Rienzo A. 2011. Adaptations to climate-mediated selective pressures in humans. PLoS Genet. 7:e1001375.
40. Hancock AM, Witonsky DB, Ehler E, et al. (11 co-authors). 2010. Colloquium paper: human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proc Natl Acad Sci U S A. 107(Suppl 2), 8924-8930.
41. Harding RM, Healy E, Ray AJ, et al. (11 co-authors). 2000. Evidence for variable selective pressures at MC1R. Am J Hum Genet. 66: 1351-1361. (Pubitemid 30468790)
42. Harris HE, Andersson U. 2004. The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 34:1503-1512. (Pubitemid 39256031)
43. Heaton NS, Randall G. 2010. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microb. 8:422-432.
44. Hebeis B, Vigorito E, Kovesdi D, Turner M. 2005. Vav proteins are required for B-lymphocyte responses to LPS. Blood 106:635-640. (Pubitemid 40981261)
45. Hedrick PW. 2011. Population genetics of malaria resistance in humans. Heredity 107:283-304.
46. Hennet T, Chui D, Paulson JC, Marth JD. 1998. Immune regulation by the ST6Gal sialyltransferase. Proc Natl Acad Sci U S A. 95: 4504-4509. (Pubitemid 128620781)
47. Hernandez RD, Kelley JL, Elyashiv E, Melton SC, Auton A, McVean G, Sella G, Przeworski M. 2011. Classic selective sweeps were rare in recent human evolution. Science 331:920-924.
48. Herroeder S, Reichardt P, Sassmann A, et al. (14 co-authors). 2009. Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility. Immunity 30:708-720.
49. Hofer T, Foll M, Excoffier L. 2012. Evolutionary forces shaping genomic islands of population differentiation in humans. BMC Genomics 13:107.
50. Holden M, Deng S, Wojnowski L, Kulle B. 2008. GSEA-SNP: applying gene set enrichment analysis to SNP data from genome-wide association studies. Bioinformatics 24:2784-2785. (Pubitemid 352722627)
51. Iglewicz B, Hoaglin DC. 1993. How to detect and handle outliers. Milwaukee (WI): ASQC Quality Press.
52. Innan H, Kim Y. 2008. Detecting local adaptation using the joint sampling of polymorphism data in the parental and derived populations. Genetics 179:1713-1720.
53. Izagirre N, Garcia I, Junquera C, de la Rua C, Alonso S. 2006. A scan for signatures of positive selection in candidate loci for skin pigmentation in humans. Mol Biol Evol. 23:1697-1706. (Pubitemid 44309763)
54. Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. 2001. Immunobiology: the immune system in health and disease. New York: Garland Science.
55. Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M. 2012. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 40:D109-D114.
56. Kayser M, Brauer S, Stoneking M. 2003. A genome scan to detect candidate regions influenced by local natural selection in human populations. Mol Biol Evol. 20:893-900. (Pubitemid 36578715)
57. Keinan A, Reich D. 2010. Human population differentiation is strongly correlated with local recombination rate. PLoS Genet. 6: e1000886.
58. Kim SY, Volsky DJ. 2005. PAGE: parametric analysis of gene set enrichment. BMC Bioinformatics 6:144.
59. Kishimoto T. 2010. IL-6: from its discovery to clinical applications. Int Immunol. 22:347-352.
60. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA. 2009. Circos: an information aesthetic for comparative genomics. Genome Res. 19:1639-1645.
61. LecuitM, Hurme R, Pizarro-Cerda J, Ohayon H, Geiger B, Cossart P. 2000. A role for alpha-and beta-catenins in bacterial uptake. Proc Natl Acad Sci U S A. 97:10008-10013.
62. Li JZ, Absher DM, Tang H, et al. (11 co-authors). 2008. Worldwide human relationships inferred from genome-wide patterns of variation. Science 319:1100-1104. (Pubitemid 351300793)
63. Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G. 2012. Systematic identification of type I and type II interferon-induced antiviral factors. Proc Natl Acad Sci U S A. 109:4239-4244.
64. Lohmueller KE, Albrechtsen A, Li Y, et al. (20 co-authors). 2011. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genet. 7:e1002326.
65. Lotze MT, Tracey KJ. 2005. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 5: 331-342. (Pubitemid 40516158)
66. Maglott D, Ostell J, Pruitt KD, Tatusova T. 2011. Entrez Gene: genecentered information at NCBI. Nucleic Acids Res. 39:D52-D57.
67. Manry J, Laval G, Patin E, et al. (12 co-authors). 2011. Evolutionary genetic dissection of human interferons. J ExpMed. 208:2747-2759.
68. Matthews L, Gopinath G, Gillespie M, et al. (20 co-authors). 2009. Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 37:D619-D622.
69. McDougall I, Brown FH, Fleagle JG. 2005. Stratigraphic placement and age of modern humans from Kibish, Ethiopia. Nature 433: 733-736. (Pubitemid 40292980)
70. Menashe I, Maeder D, Garcia-Closas M, et al. (11 co-authors). 2010. Pathway analysis of breast cancer genome-wide association study highlights three pathways and one canonical signaling cascade. Cancer Res. 70:4453-4459.
71. Merico D, Isserlin R, Stueker O, Emili A, Bader GD. 2010. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 5:e13984.
72. Mootha VK, Lindgren CM, Eriksson KF, et al. (21 co-authors). 2003. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 34: 267-273. (Pubitemid 36792858)
73. Nam D, Kim J, Kim SY, Kim S. 2010. GSA-SNP: a general approach for gene set analysis of polymorphisms. Nucleic Acids Res. 38: W749-W754.
74. Nawijn MC, Hackett TL, Postma DS, van Oosterhout AJ, Heijink IH. 2011. E-cadherin: gatekeeper of airway mucosa and allergic sensitization. Trends Immunol. 32:248-255.
75. Nettleton D, Hwang JTG, Caldo RA, Wise RP. 2006. Estimating the number of true null hypotheses from a histogram of p values. J Agric Biol Environ Stat. 11:337-356. (Pubitemid 44383308)
76. Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG. 2007. Recent and ongoing selection in the human genome. Nat Rev Genet. 8: 857-868. (Pubitemid 47609088)
77. Nielsen R, Williamson S, Kim Y, Hubisz MJ, Clark AG, Bustamante C. 2005. Genomic scans for selective sweeps using SNP data. Genome Res. 15:1566-1575. (Pubitemid 41545010)
78. Pavlidis P, Jensen JD, Stephan W. 2010. Searching for footprints of positive selection in whole-genome SNP data from nonequilibrium populations. Genetics 185:907-922.
79. Pavlidis P, Jensen JD, Stephan W, Stamatakis A. 2012. A critical assessment of storytelling: gene ontology categories and the importance of validating genomic scans. Mol Biol Evol. 29:3237-3248.
80. Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi Y. 2009. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460:103-107.
81. Phillips PC. 2008. Epistasis - the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet. 9: 855-867.
82. Portugal S, Carret C, Recker M, et al. (11 co-authors). 2011. Hostmediated regulation of superinfection in malaria. Nat Med. 17: 732-737.
83. Pritchard JK, Pickrell JK, Coop G. 2010. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr Biol. 20:R208-R215.
84. R Development Core Team. 2009. R: a language and environment for statistical computing. Vienna (Austria): R Foundation for Statistical Computing.
85. Rice JA. 2007. Mathematical statistics and data analysis. Belmont (CA): Thomson/Brooks/Cole.
86. Rosenberg NA. 2006. Standardized subsets of the HGDP-CEPH human genome diversity cell line panel, accounting for atypical and duplicated samples and pairs of close relatives. Ann Hum Genet. 70:841-847. (Pubitemid 44530648)
87. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA, Feldman MW. 2002. Genetic structure of human populations. Science 298:2381-2385. (Pubitemid 36014209)
88. Rudrabhatla RS, Selvaraj SK, Prasadarao NV. 2006. Role of Rac1 in Escherichia coli K1 invasion of human brain microvascular endothelial cells. Microbes Infect. 8:460-469. (Pubitemid 43214609)
89. Ruff C. 2002. Variation in human body size and shape. Annu Rev Anthropol. 31:211-232. (Pubitemid 38973449)
90. Sabeti PC, Varilly P, Fry B, et al. (244 co-authors). 2007. Genome-wide detection and characterization of positive selection in human populations. Nature 449:913-918. (Pubitemid 47598625)
91. Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, Hannay T, Buetow KH. 2009. PID: the Pathway interaction database. Nucleic Acids Res. 37:D674-D679.
92. Shaw RK, Smollett K, Cleary J, Garmendia J, Straatman-Iwanowska A, Frankel G, Knutton S. 2005. Enteropathogenic Escherichia coli type III effectors EspG and EspG2 disrupt the microtubule network of intestinal epithelial cells. Infect Immun. 73:4385-4390. (Pubitemid 40923185)
93. Shriver LP, Manchester M. 2012. Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis. Sci Rep. 1:79.
94. Smith KF, Guegan JF. 2010. Changing geographic distributions of human pathogens. Annu Rev Ecol Evol Syst. 41:231-250.
95. SmootME, Ono K, Ruscheinski J, Wang PL, Ideker T. 2011. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431-432.
96. Storey JD, Tibshirani R. 2003. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 100:9440-9445. (Pubitemid 37033947)
97. Storz JF, Payseur BA, Nachman MW. 2004. Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa. Mol Biol Evol. 21:1800-1811. (Pubitemid 39096896)
98. Stranger BE, Stahl EA, Raj T. 2011. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics 187: 367-383.
99. Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. 2007. GSEA-P: a desktop application for gene set enrichment analysis. Bioinformatics 23:3251-3253. (Pubitemid 350187532)
100. Subramanian A, Tamayo P, Mootha VK, et al. (11 co-authors). 2005. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 102:15545-15550. (Pubitemid 41528093)
101. Sung CH, Chuang JZ. 2010. The cell biology of vision. J Cell Biol. 190: 953-963.
102. Sweet-Cordero A, Mukherjee S, Subramanian A, You H, Roix JJ, Ladd- Acosta C, Mesirov J, Golub TR, Jacks T. 2005. An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Nat Genet. 37:48-55. (Pubitemid 40070939)
103. Tintle NL, Best AA, DeJongh M, Van Bruggen D, Heffron F, Porwollik S, Taylor RC. 2008. Gene set analyses for interpreting microarray experiments on prokaryotic organisms. BMC Bioinformatics 9:469.
104. Tintle NL, Borchers B, Brown M, Bekmetjev A. 2009. Comparing gene set analysis methods on single-nucleotide polymorphism data from Genetic Analysis Workshop 16. BMC Proc. 3(7 Suppl):S96.
105. Tsai CA, Chen JJ. 2009. Multivariate analysis of variance test for gene set analysis. Bioinformatics 25:897-903.
106. Tybulewicz VL. 2005. Vav-family proteins in T-cell signalling. Curr Opin Immunol. 17:267-274. (Pubitemid 40692661)
107. Van den Bossche J, Malissen B, Mantovani A, De Baetselier P, Van Ginderachter JA. 2012. Regulation and function of the E-cadherin/ catenin complex in cells of the monocyte-macrophage lineage and DCs. Blood 119:1623-1633.
108. van der Meer-Janssen YP, van Galen J, Batenburg JJ, Helms JB. 2009. Lipids in host-pathogen interactions: pathogens exploit the complexity of the host cell lipidome. Prog Lipid Res. 49:1-26.
109. Varki A. 2009. Essentials of glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press.
110. Vasta GR. 2009. Roles of galectins in infection. Nat Rev Microbiol. 7: 424-438.
111. Vigorito E, Gambardella L, Colucci F, McAdam S, Turner M. 2005. Vav proteins regulate peripheral B-cell survival. Blood 106:2391-2398. (Pubitemid 41510812)
112. Voight BF, Kudaravalli S, Wen X, Pritchard JK. 2006. A map of recent positive selection in the human genome. PLoS Biol. 4:e72.
113. Wang ET, Kodama G, Baldi P, Moyzis RK. 2006. Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc Natl Acad Sci U S A. 103:135-140. (Pubitemid 43076117)
114. Wang K, Li M, Bucan M. 2007. Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet. 81: 1278-1283. (Pubitemid 350211456)
115. Weir BS. 1996. Genetic data analysis II: methods for discrete population genetic data. Sunderland (MA): Sinauer Associates.
116. Wettschureck N, Offermanns S. 2005. Mammalian G proteins and their cell type specific functions. Physiol Rev. 85:1159-1204. (Pubitemid 41362268)
117. Williamson SH, Hubisz MJ, Clark AG, Payseur BA, Bustamante CD, Nielsen R. 2007. Localizing recent adaptive evolution in the human genome. PLoS Genet. 3:e90.
118. Yoshida S, Sasakawa C. 2003. Exploiting host microtubule dynamics: a new aspect of bacterial invasion. Trends Microbiol. 11:139-143. (Pubitemid 36332134)
119. Young JH, Chang YP, Kim JD, Chretien JP, Klag MJ, Levine MA, Ruff CB, Wang NY, Chakravarti A. 2005. Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion. PLoS Genet. 1:e82.
120. Zhai W, Nielsen R, Slatkin M. 2009. An investigation of the statistical power of neutrality tests based on comparative and population genetic data. Mol Biol Evol. 26:273-283.
121. Zhang K, Cui S, Chang S, Zhang L, Wang J. 2010. i-GSEA4GWAS: a web server for identification of pathways/gene sets associated with traits by applying an improved gene set enrichment analysis to genome-wide association study. Nucleic Acids Res. 38: W90-W95.