Living in an adaptive world: Genomic dissection of the genus Homo and its immune response

Journal of Experimental Medicine

Volumn 214, Issue 4, 2017, Pages 877-894

  Quach, Hélène ^a,b   Quintana Murci, Lluis ^a,b  

^a INSTITUT PASTEUR   (France)

^b CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ASSOCIATION; ECOLOGICAL GENETICS; ENVIRONMENTAL FACTOR; EVOLUTIONARY ADAPTATION; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENETIC RISK; GENETIC VARIABILITY; GENOME ANALYSIS; GENUS; HOST; HUMAN; HUMAN GENOME; IMMUNE RESPONSE; IMMUNOPATHOLOGY; IMMUNOREGULATION; INFECTION; NATURAL SELECTION; PHENOTYPIC VARIATION; POPULATION; POPULATION GENETICS; PRIORITY JOURNAL; PURIFYING SELECTION; QUANTITATIVE TRAIT LOCUS; QUANTITATIVE TRAIT LOCUS MAPPING; REVIEW; SURVIVAL RATE; ADAPTATION; GENETIC SELECTION; GENETIC VARIATION; IMMUNITY; MUTATION;

ADAPTATION, BIOLOGICAL; GENETIC VARIATION; GENOME, HUMAN; HUMANS; IMMUNITY; MUTATION; QUANTITATIVE TRAIT LOCI; SELECTION, GENETIC;

EID: 85022100142     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20161942     Document Type: Review

References (177)

1. Abecasis, G.R., D. Altshuler, A. Auton, L.D. Brooks, R.M. Durbin, R.A. Gibbs, M.E. Hurles, and G.A. McVean. 1000 Genomes Project Consortium. 2010. A map of human genome variation from populationscale sequencing. Nature. 467:1061-1073. http ://dx .doi .org/10 .1038/nature09534
2. Abecasis, G.R., A. Auton, L.D. Brooks, M.A. DePristo, R.M. Durbin, R.E. Handsaker, H.M. Kang, G.T. Marth, and G.A. McVean. 1000 Genomes Project Consortium. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature. 491:56-65. http ://dx .doi .org/10 .1038/nature11632
3. Abel, L., A. Alcaïs, and E. Schurr. 2014. The dissection of complex susceptibility to infectious disease: bacterial, viral and parasitic infections. Curr. Opin. Immunol. 30:72-78. http ://dx .doi .org/10 .1016/j .coi .2014 .07 .002
4. Abi-Rached, L., M.J. Jobin, S. Kulkarni, A. McWhinnie, K. Dalva, L. Gragert, F. Babrzadeh, B. Gharizadeh, M. Luo, F.A. Plummer, et al. 2011. The shaping of modern human immune systems by multiregional admixture with archaic humans. Science. 334:89-94. http ://dx .doi .org/10 .1126/science .1209202
5. Alcaïs, A., L. Quintana-Murci, D.S. Thaler, E. Schurr, L. Abel, and J.L. Casanova. 2010. Life-threatening infectious diseases of childhood: singlegene inborn errors of immunity? Ann. N. Y. Acad. Sci. 1214:18-33. http ://dx .doi .org/10 .1111/j .1749-6632 .2010 .05834 .x
6. Andersen, K.G., I. Shylakhter, S. Tabrizi, S.R. Grossman, C.T. Happi, and P.C. Sabeti. 2012. Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367:868-877. http ://dx .doi .org/10 .1098/rstb .2011 .0299
7. Andrés, A.M., M.J. Hubisz, A. Indap, D.G. Torgerson, J.D. Degenhardt, A.R. Boyko, R.N. Gutenkunst, T.J. White, E.D. Green, C.D. Bustamante, et al. 2009. Targets of balancing selection in the human genome. Mol. Biol. Evol. 26:2755-2764. http ://dx .doi .org/10 .1093/molbev/msp190
8. Auton, A., L.D. Brooks, R.M. Durbin, E.P. Garrison, H.M. Kang, J.O. Korbel, J.L. Marchini, S. McCarthy, G.A. McVean, and G.R. Abecasis. 1000 Genomes Project Consortium. 2015. A global reference for human genetic variation. Nature. 526:68-74. http ://dx .doi .org/10 .1038/nature15393
9. Ayodo, G., A.L. Price, A. Keinan, A. Ajwang, M.F. Otieno, A.S. Orago, N. Patterson, and D. Reich. 2007. Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants. Am. J. Hum. Genet. 81:234-242. http ://dx .doi .org/10 .1086/519221
10. Barreiro, L.B., and L. Quintana-Murci. 2010. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat. Rev. Genet. 11:17-30. http ://dx .doi .org/10 .1038/nrg2698
11. Barreiro, L.B., G. Laval, H. Quach, E. Patin, and L. Quintana-Murci. 2008. Natural selection has driven population differentiation in modern humans. Nat. Genet. 40:340-345. http ://dx .doi .org/10 .1038/ng .78
12. Barreiro, L.B., M. Ben-Ali, H. Quach, G. Laval, E. Patin, J.K. Pickrell, C. Bouchier, M. Tichit, O. Neyrolles, B. Gicquel, et al. 2009. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 5:e1000562. http ://dx .doi .org/10 .1371/journal .pgen .1000562
13. Barreiro, L.B., L. Tailleux, A.A. Pai, B. Gicquel, J.C. Marioni, and Y. Gilad. 2012. Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA. 109:1204-1209. http ://dx .doi .org/10 .1073/pnas .1115761109
14. Battle, A., Z. Khan, S.H. Wang, A. Mitrano, M.J. Ford, J.K. Pritchard, and Y. Gilad. 2015. Genomic variation. Impact of regulatory variation from RNA to protein. Science. 347:664-667. http ://dx .doi .org/10 .1126/science .1260793
15. Beleza, S., A.M. Santos, B. McEvoy, I. Alves, C. Martinho, E. Cameron, M.D. Shriver, E.J. Parra, and J. Rocha. 2013. The timing of pigmentation lightening in Europeans. Mol. Biol. Evol. 30:24-35. http ://dx .doi .org/10 .1093/molbev/mss207
16. Bersaglieri, T., P.C. Sabeti, N. Patterson, T. Vanderploeg, S.F. Schaffner, J.A. Drake, M. Rhodes, D.E. Reich, and J.N. Hirschhorn. 2004. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74:1111-1120. http ://dx .doi .org/10 .1086/421051
17. Bhatia, G., N. Patterson, B. Pasaniuc, N. Zaitlen, G. Genovese, S. Pollack, S. Mallick, S. Myers, A. Tandon, C. Spencer, et al. 2011. Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection. Am. J. Hum. Genet. 89:368-381. http ://dx .doi .org/10 .1016/j .ajhg .2011 .07 .025
18. Bigham, A., M. Bauchet, D. Pinto, X. Mao, J.M. Akey, R. Mei, S.W. Scherer, C.G. Julian, M.J. Wilson, D. López Herráez, et al. 2010. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Genet. 6:e1001116. http ://dx .doi .org/10 .1371/journal .pgen .1001116
19. Boisson-Dupuis, S., X.F. Kong, S. Okada, S. Cypowyj, A. Puel, L. Abel, and J.L. Casanova. 2012. Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes. Curr. Opin. Immunol. 24:364-378. http ://dx .doi .org/10 .1016/j .coi .2012 .04 .011
20. Brinkworth, J.F., and L.B. Barreiro. 2014. The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease. Curr. Opin. Immunol. 31:66-78. http ://dx .doi .org/10 .1016/j .coi .2014 .09 .008
21. Brodin, P., and M.M. Davis. 2017. Human immune system variation. Nat. Rev. Immunol. 17:21-29. http ://dx .doi .org/10 .1038/nri .2016 .125
22. Brodin, P., V. Jojic, T. Gao, S. Bhattacharya, C.J. Angel, D. Furman, S. Shen-Orr, C.L. Dekker, G.E. Swan, A.J. Butte, et al. 2015. Variation in the human immune system is largely driven by non-heritable influences. Cell. 160:37-47. http ://dx .doi .org/10 .1016/j .cell .2014 .12 .020
23. Bryc, K., A. Auton, M.R. Nelson, J.R. Oksenberg, S.L. Hauser, S. Williams, A. Froment, J.M. Bodo, C. Wambebe, S.A. Tishkoff, and C.D. Bustamante. 2010. Genome-wide patterns of population structure and admixture in West Africans and African Americans. Proc. Natl. Acad. Sci. USA. 107:786-791. http ://dx .doi .org/10 .1073/pnas .0909559107
24. Bryk, J., E. Hardouin, I. Pugach, D. Hughes, R. Strotmann, M. Stoneking, and S. Myles. 2008. Positive selection in East Asians for an EDAR allele that enhances NF-kappaB activation. PLoS One. 3:e2209. http ://dx .doi .org/10 .1371/journal .pone .0002209
25. Bustamante, C.D., A. Fledel-Alon, S. Williamson, R. Nielsen, M.T. Hubisz, S. Glanowski, D.M. Tanenbaum, T.J. White, J.J. Sninsky, R.D. Hernandez, et al. 2005. Natural selection on protein-coding genes in the human genome. Nature. 437:1153-1157. http ://dx .doi .org/10 .1038/nature04240
26. çaliskan, M., S.W. Baker, Y. Gilad, and C. Ober. 2015. Host genetic variation influences gene expression response to rhinovirus infection. PLoS Genet. 11:e1005111. http ://dx .doi .org/10 .1371/journal .pgen .1005111
27. Campbell, M.C., J.B. Hirbo, J.P. Townsend, and S.A. Tishkoff. 2014. The peopling of the African continent and the diaspora into the new world. Curr. Opin. Genet. Dev. 29:120-132. http ://dx .doi .org/10 .1016/j .gde .2014 .09 .003
28. Casals, F., A. Hodgkinson, J. Hussin, Y. Idaghdour, V. Bruat, T. de Maillard, J.C. Grenier, E. Gbeha, F.F. Hamdan, S. Girard, et al. 2013. Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans. PLoS Genet. 9:e1003815. http ://dx .doi .org/10 .1371/journal .pgen .1003815
29. Casanova, J.L., L. Abel, and L. Quintana-Murci. 2013. Immunology taught by human genetics. Cold Spring Harb. Symp. Quant. Biol. 78:157-172. http ://dx .doi .org/10 .1101/sqb .2013 .78 .019968
30. Charlesworth, D. 2006. Balancing selection and its effects on sequences in nearby genome regions. PLoS Genet. 2:e64. http ://dx .doi .org/10 .1371/journal .pgen .0020064
31. Chen, L., B. Ge, F.P. Casale, L. Vasquez, T. Kwan, D. Garrido-Martín, S. Watt, Y. Yan, K. Kundu, S. Ecker, et al. 2016. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell. 167:1398-1414.e24. http ://dx .doi .org/10 .1016/j .cell .2016 .10 .026
32. Dannemann, M., A.M. Andrés, and J. Kelso. 2016. Introgression of Neandertaland Denisovan-like haplotypes contributes to adaptive variation in human Toll-like receptors. Am. J. Hum. Genet. 98:22-33. http ://dx .doi .org/10 .1016/j .ajhg .2015 .11 .015
33. DeGiorgio, M., K.E. Lohmueller, and R. Nielsen. 2014. A model-based approach for identifying signatures of ancient balancing selection in genetic data. PLoS Genet. 10:e1004561. http ://dx .doi .org/10 .1371/journal .pgen .1004561
34. Deschamps, M., G. Laval, M. Fagny, Y. Itan, L. Abel, J.L. Casanova, E. Patin, and L. Quintana-Murci. 2016. Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes. Am. J. Hum. Genet. 98:5-21. http ://dx .doi .org/10 .1016/j .ajhg .2015 .11 .014
35. Dimas, A.S., S. Deutsch, B.E. Stranger, S.B. Montgomery, C. Borel, H. Attar-Cohen, C. Ingle, C. Beazley, M. Gutierrez Arcelus, M. Sekowska, et al. 2009. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 325:1246-1250. http ://dx .doi .org/10 .1126/science .1174148
36. Do, R., D. Balick, H. Li, I. Adzhubei, S. Sunyaev, and D. Reich. 2015. No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans. Nat. Genet. 47:126-131. http ://dx .doi .org/10 .1038/ng .3186
37. Enattah, N.S., T. Sahi, E. Savilahti, J.D. Terwilliger, L. Peltonen, and I. Järvelä. 2002. Identification of a variant associated with adult-type hypolactasia. Nat. Genet. 30:233-237. http ://dx .doi .org/10 .1038/ng826
38. Eyre-Walker, A., and P.D. Keightley. 1999. High genomic deleterious mutation rates in hominids. Nature. 397:344-347. http ://dx .doi .org/10 .1038/16915
39. Fairfax, B.P., and J.C. Knight. 2014. Genetics of gene expression in immunity to infection. Curr. Opin. Immunol. 30:63-71. http ://dx .doi .org/10 .1016/j .coi .2014 .07 .001
40. Fairfax, B.P., S. Makino, J. Radhakrishnan, K. Plant, S. Leslie, A. Dilthey, P. Ellis, C. Langford, F.O. Vannberg, and J.C. Knight. 2012. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat. Genet. 44:502-510. http ://dx .doi .org/10 .1038/ng .2205
41. Fairfax, B.P., P. Humburg, S. Makino, V. Naranbhai, D. Wong, E. Lau, L. Jostins, K. Plant, R. Andrews, C. McGee, and J.C. Knight. 2014. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science. 343:1246949. http ://dx .doi .org/10 .1126/science .1246949
42. Fan, S., M.E. Hansen, Y. Lo, and S.A. Tishkoff. 2016. Going global by adapting local: A review of recent human adaptation. Science. 354:54-59. http ://dx .doi .org/10 .1126/science .aaf5098
43. Field, Y., E.A. Boyle, N. Telis, Z. Gao, K.J. Gaulton, D. Golan, L. Yengo, G. Rocheleau, P. Froguel, M.I. McCarthy, and J.K. Pritchard. 2016. Detection of human adaptation during the past 2000 years. Science. 354:760-764. http ://dx .doi .org/10 .1126/science .aag0776
44. Fraser, H.B. 2013. Gene expression drives local adaptation in humans. Genome Res. 23:1089-1096. http ://dx .doi .org/10 .1101/gr .152710 .112
45. Fry, A.E., A. Ghansa, K.S. Small, A. Palma, S. Auburn, M. Diakite, A. Green, S. Campino, Y.Y. Teo, T.G. Clark, et al. 2009. Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes. Hum. Mol. Genet. 18:2683-2692. http ://dx .doi .org/10 .1093/hmg/ddp192
46. Fu, Q., C. Posth, M. Hajdinjak, M. Petr, S. Mallick, D. Fernandes, A. Furtwängler, W. Haak, M. Meyer, A. Mittnik, et al. 2016. The genetic history of Ice Age Europe. Nature. 534:200-205. http ://dx .doi .org/10 .1038/nature17993
47. Fu, W., T.D. O'Connor, G. Jun, H.M. Kang, G. Abecasis, S.M. Leal, S. Gabriel, M.J. Rieder, D. Altshuler, J. Shendure, et al. NHL BI Exome Sequencing Project. 2013. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature. 493:216-220. http ://dx .doi .org/10 .1038/nature11690
48. Fu, W., R.M. Gittelman, M.J. Bamshad, and J.M. Akey. 2014. Characteristics of neutral and deleterious protein-coding variation among individuals and populations. Am. J. Hum. Genet. 95:421-436. http ://dx .doi .org/10 .1016/j .ajhg .2014 .09 .006
49. Fumagalli, M., and M. Sironi. 2014. Human genome variability, natural selection and infectious diseases. Curr. Opin. Immunol. 30:9-16. http ://dx .doi .org/10 .1016/j .coi .2014 .05 .001
50. Fumagalli, M., M. Sironi, U. Pozzoli, A. Ferrer-Admetlla, L. Pattini, and R. Nielsen. 2011. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet. 7:e1002355. http ://dx .doi .org/10 .1371/journal .pgen .1002355
51. Gaulton, K.J., T. Nammo, L. Pasquali, J.M. Simon, P.G. Giresi, M.P. Fogarty, T.M. Panhuis, P. Mieczkowski, A. Secchi, D. Bosco, et al. 2010. A map of open chromatin in human pancreatic islets. Nat. Genet. 42:255-259. http ://dx .doi .org/10 .1038/ng .530
52. Green, R.E., J. Krause, A.W. Briggs, T. Maricic, U. Stenzel, M. Kircher, N. Patterson, H. Li, W. Zhai, M.H. Fritz, et al. 2010. A draft sequence of the Neandertal genome. Science. 328:710-722. http ://dx .doi .org/10 .1126/science .1188021
53. Gregory, A.P., C.A. Dendrou, K.E. Attfield, A. Haghikia, D.K. Xifara, F. Butter, G. Poschmann, G. Kaur, L. Lambert, O.A. Leach, et al. 2012. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 488:508-511. http ://dx .doi .org/10 .1038/nature11307
54. Grossman, S.R., I. Shlyakhter, E.K. Karlsson, E.H. Byrne, S. Morales, G. Frieden, E. Hostetter, E. Angelino, M. Garber, O. Zuk, et al. 2010. A composite of multiple signals distinguishes causal variants in regions of positive selection. Science. 327:883-886. http ://dx .doi .org/10 .1126/science .1183863
55. Grossman, S.R., K.G. Andersen, I. Shlyakhter, S. Tabrizi, S. Winnicki, A. Yen, D.J. Park, D. Griesemer, E.K. Karlsson, S.H. Wong, et al. 1000 Genomes Project. 2013. Identifying recent adaptations in large-scale genomic data. Cell. 152:703-713. http ://dx .doi .org/10 .1016/j .cell .2013 .01 .035
56. GTEx Consortium. 2015. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 348:648-660. http ://dx .doi .org/10 .1126/science .1262110
57. Gutenkunst, R.N., R.D. Hernandez, S.H. Williamson, and C.D. Bustamante. 2009. Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet. 5:e1000695. http ://dx .doi .org/10 .1371/journal .pgen .1000695
58. Hamblin, M.T., and A. Di Rienzo. 2000. Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. Am. J. Hum. Genet. 66:1669-1679. http ://dx .doi .org/10 .1086/302879
59. Hamblin, M.T., E.E. Thompson, and A. Di Rienzo. 2002. Complex signatures of natural selection at the Duffy blood group locus. Am. J. Hum. Genet. 70:369-383. http ://dx .doi .org/10 .1086/338628
60. Hammer, M.F., A.E. Woerner, F.L. Mendez, J.C. Watkins, and J.D. Wall. 2011. Genetic evidence for archaic admixture in Africa. Proc. Natl. Acad. Sci. USA. 108:15123-15128. http ://dx .doi .org/10 .1073/pnas .1109300108
61. Henn, B.M., L.L. Cavalli-Sforza, and M.W. Feldman. 2012. The great human expansion. Proc. Natl. Acad. Sci. USA. 109:17758-17764. http ://dx .doi .org/10 .1073/pnas .1212380109
62. Henn, B.M., L.R. Botigué, C.D. Bustamante, A.G. Clark, and S. Gravel. 2015. Estimating the mutation load in human genomes. Nat. Rev. Genet. 16:333-343. http ://dx .doi .org/10 .1038/nrg3931
63. Henn, B.M., L.R. Botigué, S. Peischl, I. Dupanloup, M. Lipatov, B.K. Maples, A.R. Martin, S. Musharoff, H. Cann, M.P. Snyder, et al. 2016. Distance from sub-Saharan Africa predicts mutational load in diverse human genomes. Proc. Natl. Acad. Sci. USA. 113:E440-E449. http ://dx .doi .org/10 .1073/pnas .1510805112
64. Hindorff, L.A., P. Sethupathy, H.A. Junkins, E.M. Ramos, J.P. Mehta, F.S. Collins, and T.A. Manolio. 2009. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA. 106:9362-9367. http ://dx .doi .org/10 .1073/pnas .0903103106
65. Holsinger, K.E., and B.S. Weir. 2009. Genetics in geographically structured populations: defining, estimating and interpreting F(ST). Nat. Rev. Genet. 10:639-650. http ://dx .doi .org/10 .1038/nrg2611
66. Huerta-Sánchez, E., X. Jin, Z. Asan, Z. Bianba, B.M. Peter, N. Vinckenbosch, Y. Liang, X. Yi, M. He, M. Somel, et al. 2014. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature. 512:194-197. http ://dx .doi .org/10 .1038/nature13408
67. Hunt, K.A., A. Zhernakova, G. Turner, G.A. Heap, L. Franke, M. Bruinenberg, J. Romanos, L.C. Dinesen, A.W. Ryan, D. Panesar, et al. 2008. Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet. 40:395-402. http ://dx .doi .org/10 .1038/ng .102
68. Itan, Y., A. Powell, M.A. Beaumont, J. Burger, and M.G. Thomas. 2009. The origins of lactase persistence in Europe. PLOS Comput. Biol. 5:e1000491. http ://dx .doi .org/10 .1371/journal .pcbi .1000491
69. Jakobsson, M., S.W. Scholz, P. Scheet, J.R. Gibbs, J.M. VanLiere, H.C. Fung, Z.A. Szpiech, J.H. Degnan, K. Wang, R. Guerreiro, et al. 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature. 451:998-1003. http ://dx .doi .org/10 .1038/nature06742
70. Jarvis, J.P., L.B. Scheinfeldt, S. Soi, C. Lambert, L. Omberg, B. Ferwerda, A. Froment, J.M. Bodo, W. Beggs, G. Hoffman, et al. 2012. Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies. PLoS Genet. 8:e1002641. http ://dx .doi .org/10 .1371/journal .pgen .1002641
71. Jeong, C., and A. Di Rienzo. 2014. Adaptations to local environments in modern human populations. Curr. Opin. Genet. Dev. 29:1-8. http ://dx .doi .org/10 .1016/j .gde .2014 .06 .011
72. Kang, J.Y., A.H. Kang, A. Green, K.A. Gwee, and K.Y. Ho. 2013. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Aliment. Pharmacol. Ther. 38:226-245. http ://dx .doi .org/10 .1111/apt .12373
73. Karlsson, E.K., D.P. Kwiatkowski, and P.C. Sabeti. 2014. Natural selection and infectious disease in human populations. Nat. Rev. Genet. 15:379-393. http ://dx .doi .org/10 .1038/nrg3734
74. Kelso, J., and K. Prüfer. 2014. Ancient humans and the origin of modern humans. Curr. Opin. Genet. Dev. 29:133-138. http ://dx .doi .org/10 .1016/j .gde .2014 .09 .004
75. Key, F.M., B. Peter, M.Y. Dennis, E. Huerta-Sánchez, W. Tang, L. Prokunina-Olsson, R. Nielsen, and A.M. Andrés. 2014a. Selection on a variant associated with improved viral clearance drives local, adaptive pseudogenization of interferon lambda 4 (IFNL4). PLoS Genet. 10:e1004681. http ://dx .doi .org/10 .1371/journal .pgen .1004681
76. Key, F.M., J.C. Teixeira, C. de Filippo, and A.M. Andrés. 2014b. Advantageous diversity maintained by balancing selection in humans. Curr. Opin. Genet. Dev. 29:45-51. http ://dx .doi .org/10 .1016/j .gde .2014 .08 .001
77. Konopka, G., and T.F. Roberts. 2016. Insights into the neural and genetic basis of vocal communication. Cell. 164:1269-1276. http ://dx .doi .org/10 .1016/j .cell .2016 .02 .039
78. Kreitman, M. 2000. Methods to detect selection in populations with applications to the human. Annu. Rev. Genomics Hum. Genet. 1:539-559. http ://dx .doi .org/10 .1146/annurev .genom .1 .1 .539
79. Kryukov, G.V., L.A. Pennacchio, and S.R. Sunyaev. 2007. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80:727-739. http ://dx .doi .org/10 .1086/513473
80. Kwiatkowski, D.P. 2005. How malaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet. 77:171-192. http ://dx .doi .org/10 .1086/432519
81. Lachance, J., B. Vernot, C.C. Elbers, B. Ferwerda, A. Froment, J.M. Bodo, G. Lema, W. Fu, T.B. Nyambo, T.R. Rebbeck, et al. 2012. Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers. Cell. 150:457-469. http ://dx .doi .org/10 .1016/j .cell .2012 .07 .009
82. Lamason, R.L., M.A. Mohideen, J.R. Mest, A.C. Wong, H.L. Norton, M.C. Aros, M.J. Jurynec, X. Mao, V.R. Humphreville, J.E. Humbert, et al. 2005. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science. 310:1782-1786. http ://dx .doi .org/10 .1126/science .1116238
83. Lee, M.N., C. Ye, A.C. Villani, T. Raj, W. Li, T.M. Eisenhaure, S.H. Imboywa, P.I. Chipendo, F.A. Ran, K. Slowikowski, et al. 2014. Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science. 343:1246980. http ://dx .doi .org/10 .1126/science .1246980
84. Leffler, E.M., Z. Gao, S. Pfeifer, L. Ségurel, A. Auton, O. Venn, R. Bowden, R. Bontrop, J.D. Wall, G. Sella, et al. 2013. Multiple instances of ancient balancing selection shared between humans and chimpanzees. Science. 339:1578-1582. http ://dx .doi .org/10 .1126/science .1234070
85. Lek, M., K.J. Karczewski, E.V. Minikel, K.E. Samocha, E. Banks, T. Fennell, A.H. O'Donnell-Luria, J.S. Ware, A.J. Hill, B.B. Cummings, et al. Exome Aggregation Consortium. 2016. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 536:285-291. http ://dx .doi .org/10 .1038/nature19057
86. Li, Y., M. Oosting, S.P. Smeekens, M. Jaeger, R. Aguirre-Gamboa, K.T. Le, P. Deelen, I. Ricaño-Ponce, T. Schoffelen, A.F. Jansen, et al. 2016. A functional genomics approach to understand variation in cytokine production in humans. Cell. 167:1099-1110.e14. http ://dx .doi .org/10 .1016/j .cell .2016 .10 .017
87. Lim, E.T., P. Würtz, A.S. Havulinna, P. Palta, T. Tukiainen, K. Rehnström, T. Esko, R. Mägi, M. Inouye, T. Lappalainen, et al. Sequencing Initiative Suomi (SISu) Project. 2014. Distribution and medical impact of lossof-function variants in the Finnish founder population. PLoS Genet. 10:e1004494. http ://dx .doi .org/10 .1371/journal .pgen .1004494
88. Linnen, C.R., and H.E. Hoekstra. 2009. Measuring natural selection on genotypes and phenotypes in the wild. Cold Spring Harb. Symp. Quant. Biol. 74:155-168. http ://dx .doi .org/10 .1101/sqb .2009 .74 .045
89. Liston, A., E.J. Carr, and M.A. Linterman. 2016. Shaping variation in the human immune system. Trends Immunol. 37:637-646. http ://dx .doi .org/10 .1016/j .it .2016 .08 .002
90. Liu, H., A. Irwanto, X. Fu, G. Yu, Y. Yu, Y. Sun, C. Wang, Z. Wang, Y. Okada, H. Low, et al. 2015. Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy. Nat. Genet. 47:267-271. http ://dx .doi .org/10 .1038/ng .3212
91. Lohmueller, K.E. 2014. The distribution of deleterious genetic variation in human populations. Curr. Opin. Genet. Dev. 29:139-146. http ://dx .doi .org/10 .1016/j .gde .2014 .09 .005
92. Lohmueller, K.E., A.R. Indap, S. Schmidt, A.R. Boyko, R.D. Hernandez, M.J. Hubisz, J.J. Sninsky, T.J. White, S.R. Sunyaev, R. Nielsen, et al. 2008. Proportionally more deleterious genetic variation in European than in African populations. Nature. 451:994-997. http ://dx .doi .org/10 .1038/nature06611
93. Louicharoen, C., E. Patin, R. Paul, I. Nuchprayoon, B. Witoonpanich, C. Peerapittayamongkol, I. Casademont, T. Sura, N.M. Laird, P. Singhasivanon, et al. 2009. Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 326:1546-1549. http ://dx .doi .org/10 .1126/science .1178849
94. Malaspinas, A.S., M.C. Westaway, C. Muller, V.C. Sousa, O. Lao, I. Alves, A. Bergström, G. Athanasiadis, J.Y. Cheng, J.E. Crawford, et al. 2016. A genomic history of Aboriginal Australia. Nature. 538:207-214. http ://dx .doi .org/10 .1038/nature18299
95. Mallick, S., H. Li, M. Lipson, I. Mathieson, M. Gymrek, F. Racimo, M. Zhao, N. Chennagiri, S. Nordenfelt, A. Tandon, et al. 2016. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Nature. 538:201-206. http ://dx .doi .org/10 .1038/nature18964
96. Manolio, T.A., F.S. Collins, N.J. Cox, D.B. Goldstein, L.A. Hindorff, D.J. Hunter, M.I. McCarthy, E.M. Ramos, L.R. Cardon, A. Chakravarti, et al. 2009. Finding the missing heritability of complex diseases. Nature. 461:747-753. http ://dx .doi .org/10 .1038/nature08494
97. Manry, J., G. Laval, E. Patin, S. Fornarino, Y. Itan, M. Fumagalli, M. Sironi, M. Tichit, C. Bouchier, J.L. Casanova, et al. 2011. Evolutionary genetic dissection of human interferons. J. Exp. Med. 208:2747-2759. http ://dx .doi .org/10 .1084/jem .20111680
98. Mathieson, I., I. Lazaridis, N. Rohland, S. Mallick, N. Patterson, S.A. Roodenberg, E. Harney, K. Stewardson, D. Fernandes, M. Novak, et al. 2015. Genome-wide patterns of selection in 230 ancient Eurasians. Nature. 528:499-503. http ://dx .doi .org/10 .1038/nature16152
99. Mendez, F.L., J.C. Watkins, and M.F. Hammer. 2012. A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea. Am. J. Hum. Genet. 91:265-274. http ://dx .doi .org/10 .1016/j .ajhg .2012 .06 .015
100. Mendez, F.L., J.C. Watkins, and M.F. Hammer. 2013. Neandertal origin of genetic variation at the cluster of OAS immunity genes. Mol. Biol. Evol. 30:798-801. http ://dx .doi .org/10 .1093/molbev/mst004
101. Meyer, M., M. Kircher, M.T. Gansauge, H. Li, F. Racimo, S. Mallick, J.G. Schraiber, F. Jay, K. Prüfer, C. de Filippo, et al. 2012. A high-coverage genome sequence from an archaic Denisovan individual. Science. 338:222-226. http ://dx .doi .org/10 .1126/science .1224344
102. Miller, C.T., S. Beleza, A.A. Pollen, D. Schluter, R.A. Kittles, M.D. Shriver, and D.M. Kingsley. 2007. cis-Regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. Cell. 131:1179-1189. http ://dx .doi .org/10 .1016/j .cell .2007 .10 .055
103. Montgomery, S.B., and E.T. Dermitzakis. 2011. From expression QTLs to personalized transcriptomics. Nat. Rev. Genet. 12:277-282. http ://dx .doi .org/10 .1038/nrg2969
104. Montinaro, F., G.B. Busby, V.L. Pascali, S. Myers, G. Hellenthal, and C. Capelli. 2015. Unravelling the hidden ancestry of American admixed populations. Nat. Commun. 6:6596. http ://dx .doi .org/10 .1038/ncomms7596
105. Nédélec, Y., J. Sanz, G. Baharian, Z.A. Szpiech, A. Pacis, A. Dumaine, J.C. Grenier, A. Freiman, A.J. Sams, S. Hebert, et al. 2016. Genetic ancestry and natural selection drive population differences in immune responses to pathogens. Cell. 167:657-669.e21. http ://dx .doi .org/10 .1016/j .cell .2016 .09 .025
106. Newbold, C., A. Craig, S. Kyes, A. Rowe, D. Fernandez-Reyes, and T. Fagan. 1999. Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum. Int. J. Parasitol. 29:927-937. http ://dx .doi .org/10 .1016/S0020-7519(99)00049-1
107. Nica, A.C., L. Parts, D. Glass, J. Nisbet, A. Barrett, M. Sekowska, M. Travers, S. Potter, E. Grundberg, K. Small, et al. MuTHER Consortium. 2011. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet. 7:e1002003. http ://dx .doi .org/10 .1371/journal .pgen .1002003
108. Nicolae, D.L., E. Gamazon, W. Zhang, S. Duan, M.E. Dolan, and N.J. Cox. 2010. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet. 6:e1000888. http ://dx .doi .org/10 .1371/journal .pgen .1000888
109. Nielsen, R. 2005. Molecular signatures of natural selection. Annu. Rev. Genet. 39:197-218. http ://dx .doi .org/10 .1146/annurev .genet .39 .073003 .112420
110. Nielsen, R., S. Williamson, Y. Kim, M.J. Hubisz, A.G. Clark, and C. Bustamante. 2005. Genomic scans for selective sweeps using SNP data. Genome Res. 15:1566-1575. http ://dx .doi .org/10 .1101/gr .4252305
111. Nielsen, R., I. Hellmann, M. Hubisz, C. Bustamante, and A.G. Clark. 2007. Recent and ongoing selection in the human genome. Nat. Rev. Genet. 8:857-868. http ://dx .doi .org/10 .1038/nrg2187
112. Nielsen, R., J.M. Akey, M. Jakobsson, J.K. Pritchard, S. Tishkoff, and E. Willerslev. 2017. Tracing the peopling of the world through genomics. Nature. 541:302-310. http ://dx .doi .org/10 .1038/nature21347
113. Norman, P.J., L. Abi-Rached, K. Gendzekhadze, D. Korbel, M. Gleimer, D. Rowley, D. Bruno, C.V. Carrington, D. Chandanayingyong, Y.H. Chang, et al. 2007. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat. Genet. 39:1092-1099. http ://dx .doi .org/10 .1038/ng2111
114. Norton, H.L., R.A. Kittles, E. Parra, P. McKeigue, X. Mao, K. Cheng, V.A. Canfield, D.G. Bradley, B. McEvoy, and M.D. Shriver. 2007. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol. Biol. Evol. 24:710-722. http ://dx .doi .org/10 .1093/molbev/msl203
115. Novembre, J., and S. Ramachandran. 2011. Perspectives on human population structure at the cusp of the sequencing era. Annu. Rev. Genomics Hum. Genet. 12:245-274. http ://dx .doi .org/10 .1146/annurev-genom-090810-183123
116. Novembre, J., T. Johnson, K. Bryc, Z. Kutalik, A.R. Boyko, A. Auton, A. Indap, K.S. King, S. Bergmann, M.R. Nelson, et al. 2008. Genes mirror geography within Europe. Nature. 456:98-101. http ://dx .doi .org/10 .1038/nature07331
117. Orrù, V., M. Steri, G. Sole, C. Sidore, F. Virdis, M. Dei, S. Lai, M. Zoledziewska, F. Busonero, A. Mulas, et al. 2013. Genetic variants regulating immune cell levels in health and disease. Cell. 155:242-256. http ://dx .doi .org/10 .1016/j .cell .2013 .08 .041
118. Pagani, L., D.J. Lawson, E. Jagoda, A. Mörseburg, A. Eriksson, M. Mitt, F. Clemente, G. Hudjashov, M. DeGiorgio, L. Saag, et al. 2016. Genomic analyses inform on migration events during the peopling of Eurasia. Nature. 538:238-242. http ://dx .doi .org/10 .1038/nature19792
119. Parkes, M., A. Cortes, D.A. van Heel, and M.A. Brown. 2013. Genetic insights into common pathways and complex relationships among immunemediated diseases. Nat. Rev. Genet. 14:661-673. http ://dx .doi .org/10 .1038/nrg3502
120. Patin, E., K.J. Siddle, G. Laval, H. Quach, C. Harmant, N. Becker, A. Froment, B. Régnault, L. Lemée, S. Gravel, et al. 2014. The impact of agricultural emergence on the genetic history of African rainforest hunter-gatherers and agriculturalists. Nat. Commun. 5:3163. http ://dx .doi .org/10 .1038/ncomms4163
121. Peng, Y., Z. Yang, H. Zhang, C. Cui, X. Qi, X. Luo, X. Tao, T. Wu, Ouzhuluobu, Basang, et al. 2011. Genetic variations in Tibetan populations and highaltitude adaptation at the Himalayas. Mol. Biol. Evol. 28:1075-1081. http ://dx .doi .org/10 .1093/molbev/msq290
122. Pérez de Diego, R., V. Sancho-Shimizu, L. Lorenzo, A. Puel, S. Plancoulaine, C. Picard, M. Herman, A. Cardon, A. Durandy, J. Bustamante, et al. 2010. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity. 33:400-411. http ://dx .doi .org/10 .1016/j .immuni .2010 .08 .014
123. Perry, G.H., L. Kistler, M.A. Kelaita, and A.J. Sams. 2015. Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data. J. Hum. Evol. 79:55-63. http ://dx .doi .org/10 .1016/j .jhevol .2014 .10 .018
124. Pickrell, J.K. 2014. Joint analysis of functional genomic data and genomewide association studies of 18 human traits. Am. J. Hum. Genet. 94:559-573. http ://dx .doi .org/10 .1016/j .ajhg .2014 .03 .004
125. Powell, J.E., A.K. Henders, A.F. McRae, M.J. Wright, N.G. Martin, E.T. Dermitzakis, G.W. Montgomery, and P.M. Visscher. 2012. Genetic control of gene expression in whole blood and lymphoblastoid cell lines is largely independent. Genome Res. 22:456-466. http ://dx .doi .org/10 .1101/gr .126540 .111
126. Price, A.L., A. Helgason, G. Thorleifsson, S.A. McCarroll, A. Kong, and K. Stefansson. 2011. Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals. PLoS Genet. 7:e1001317. http ://dx .doi .org/10 .1371/journal .pgen .1001317
127. Pritchard, J.K., J.K. Pickrell, and G. Coop. 2010. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr. Biol. 20:R208-R215. http ://dx .doi .org/10 .1016/j .cub .2009 .11 .055
128. Prüfer, K., F. Racimo, N. Patterson, F. Jay, S. Sankararaman, S. Sawyer, A. Heinze, G. Renaud, P.H. Sudmant, C. de Filippo, et al. 2014. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 505:43-49. http ://dx .doi .org/10 .1038/nature12886
129. Quach, H., M. Rotival, J. Pothlichet, Y.E. Loh, M. Dannemann, N. Zidane, G. Laval, E. Patin, C. Harmant, M. Lopez, et al. 2016. Genetic Adaptation and Neandertal admixture shaped the immune system of human populations. Cell. 167:643-656.e17. http ://dx .doi .org/10 .1016/j .cell .2016 .09 .024
130. Quintana-Murci, L., and L.B. Barreiro. 2010. The role played by natural selection on Mendelian traits in humans. Ann. N. Y. Acad. Sci. 1214:1-17. http ://dx .doi .org/10 .1111/j .1749-6632 .2010 .05856 .x
131. Quintana-Murci, L., and A.G. Clark. 2013. Population genetic tools for dissecting innate immunity in humans. Nat. Rev. Immunol. 13:280-293. http ://dx .doi .org/10 .1038/nri3421
132. Quintana-Murci, L., A. Alcaïs, L. Abel, and J.L. Casanova. 2007. Immunology in natura: clinical, epidemiological and evolutionary genetics of infectious diseases. Nat. Immunol. 8:1165-1171. http ://dx .doi .org/10 .1038/ni1535
133. Racimo, F., S. Sankararaman, R. Nielsen, and E. Huerta-Sánchez. 2015. Evidence for archaic adaptive introgression in humans. Nat. Rev. Genet. 16:359-371. http ://dx .doi .org/10 .1038/nrg3936
134. Raj, T., K. Rothamel, S. Mostafavi, C. Ye, M.N. Lee, J.M. Replogle, T. Feng, M. Lee, N. Asinovski, I. Frohlich, et al. 2014. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science. 344:519-523. http ://dx .doi .org/10 .1126/science .1249547
135. Ranciaro, A., M.C. Campbell, J.B. Hirbo, W.Y. Ko, A. Froment, P. Anagnostou, M.J. Kotze, M. Ibrahim, T. Nyambo, S.A. Omar, and S.A. Tishkoff. 2014. Genetic origins of lactase persistence and the spread of pastoralism in Africa. Am. J. Hum. Genet. 94:496-510. http ://dx .doi .org/10 .1016/j .ajhg .2014 .02 .009
136. Reich, D., R.E. Green, M. Kircher, J. Krause, N. Patterson, E.Y. Durand, B. Viola, A.W. Briggs, U. Stenzel, P.L. Johnson, et al. 2010. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 468:1053-1060. http ://dx .doi .org/10 .1038/nature09710
137. Reich, D., N. Patterson, M. Kircher, F. Delfin, M.R. Nandineni, I. Pugach, A.M. Ko, Y.C. Ko, T.A. Jinam, M.E. Phipps, et al. 2011. Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania. Am. J. Hum. Genet. 89:516-528. http ://dx .doi .org/10 .1016/j .ajhg .2011 .09 .005
138. Roederer, M., L. Quaye, M. Mangino, M.H. Beddall, Y. Mahnke, P. Chattopadhyay, I. Tosi, L. Napolitano, M. Terranova Barberio, C. Menni, et al. 2015. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell. 161:387-403. http ://dx .doi .org/10 .1016/j .cell .2015 .02 .046
139. Ruwende, C., S.C. Khoo, R.W. Snow, S.N. Yates, D. Kwiatkowski, S. Gupta, P. Warn, C.E. Allsopp, S.C. Gilbert, N. Peschu, et al. 1995. Natural selection of hemi-and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature. 376:246-249. http ://dx .doi .org/10 .1038/376246a0
140. Sabeti, P.C., D.E. Reich, J.M. Higgins, H.Z. Levine, D.J. Richter, S.F. Schaffner, S.B. Gabriel, J.V. Platko, N.J. Patterson, G.J. McDonald, et al. 2002. Detecting recent positive selection in the human genome from haplotype structure. Nature. 419:832-837. http ://dx .doi .org/10 .1038/nature01140
141. Sabeti, P.C., S.F. Schaffner, B. Fry, J. Lohmueller, P. Varilly, O. Shamovsky, A. Palma, T.S. Mikkelsen, D. Altshuler, and E.S. Lander. 2006. Positive natural selection in the human lineage. Science. 312:1614-1620. http ://dx .doi .org/10 .1126/science .1124309
142. Sabeti, P.C., P. Varilly, B. Fry, J. Lohmueller, E. Hostetter, C. Cotsapas, X. Xie, E.H. Byrne, S.A. McCarroll, R. Gaudet, et al. International HapMap Consortium. 2007. Genome-wide detection and characterization of positive selection in human populations. Nature. 449:913-918. http ://dx .doi .org/10 .1038/nature06250
143. Sams, A.J., A. Dumaine, Y. Nédélec, V. Yotova, C. Alfieri, J.E. Tanner, P.W. Messer, and L.B. Barreiro. 2016. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans. Genome Biol. 17:246. http ://dx .doi .org/10 .1186/s13059-016-1098-6
144. Sankararaman, S., S. Mallick, M. Dannemann, K. Prüfer, J. Kelso, S. Pääbo, N. Patterson, and D. Reich. 2014. The genomic landscape of Neanderthal ancestry in present-day humans. Nature. 507:354-357. http ://dx .doi .org/10 .1038/nature12961
145. Saunders, M.A., M.F. Hammer, and M.W. Nachman. 2002. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics. 162:1849-1861
146. Schaub, M.A., A.P. Boyle, A. Kundaje, S. Batzoglou, and M. Snyder. 2012. Linking disease associations with regulatory information in the human genome. Genome Res. 22:1748-1759. http ://dx .doi .org/10 .1101/gr .136127 .111
147. Scheinfeldt, L.B., and S.A. Tishkoff. 2013. Recent human adaptation: genomic approaches, interpretation and insights. Nat. Rev. Genet. 14:692-702. http ://dx .doi .org/10 .1038/nrg3604
148. Schirmer, M., S.P. Smeekens, H. Vlamakis, M. Jaeger, M. Oosting, E.A. Franzosa, T. Jansen, L. Jacobs, M.J. Bonder, A. Kurilshikov, et al. 2016. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 167:1125-1136.e8. http ://dx .doi .org/10 .1016/j .cell .2016 .10 .020
149. Siddle, K.J., and L. Quintana-Murci. 2014. The Red Queen's long race: human adaptation to pathogen pressure. Curr. Opin. Genet. Dev. 29:31-38. http ://dx .doi .org/10 .1016/j .gde .2014 .07 .004
150. Siddle, K.J., M. Deschamps, L. Tailleux, Y. Nédélec, J. Pothlichet, G. Lugo-Villarino, V. Libri, B. Gicquel, O. Neyrolles, G. Laval, et al. 2014. A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection. Genome Res. 24:850-859. http ://dx .doi .org/10 .1101/gr .161471 .113
151. Simons, Y.B., and G. Sella. 2016. The impact of recent population history on the deleterious mutation load in humans and close evolutionary relatives. Curr. Opin. Genet. Dev. 41:150-158. http ://dx .doi .org/10 .1016/j .gde .2016 .09 .006
152. Simons, Y.B., M.C. Turchin, J.K. Pritchard, and G. Sella. 2014. The deleterious mutation load is insensitive to recent population history. Nat. Genet. 46:220-224. http ://dx .doi .org/10 .1038/ng .2896
153. Simonson, T.S., Y. Yang, C.D. Huff, H. Yun, G. Qin, D.J. Witherspoon, Z. Bai, F.R. Lorenzo, J. Xing, L.B. Jorde, et al. 2010. Genetic evidence for highaltitude adaptation in Tibet. Science. 329:72-75. http ://dx .doi .org/10 .1126/science .1189406
154. Simonti, C.N., B. Vernot, L. Bastarache, E. Bottinger, D.S. Carrell, R.L. Chisholm, D.R. Crosslin, S.J. Hebbring, G.P. Jarvik, I.J. Kullo, et al. 2016. The phenotypic legacy of admixture between modern humans and Neandertals. Science. 351:737-741. http ://dx .doi .org/10 .1126/science .aad2149
155. Single, R.M., M.P. Martin, X. Gao, D. Meyer, M. Yeager, J.R. Kidd, K.K. Kidd, and M. Carrington. 2007. Global diversity and evidence for coevolution of KIR and HLA. Nat. Genet. 39:1114-1119. http ://dx .doi .org/10 .1038/ng2077
156. Sironi, M., and M. Clerici. 2010. The hygiene hypothesis: an evolutionary perspective. Microbes Infect. 12:421-427. http ://dx .doi .org/10 .1016/j .micinf .2010 .02 .002
157. Smith, M.W., and S.J. O'Brien. 2005. Mapping by admixture linkage disequilibrium: advances, limitations and guidelines. Nat. Rev. Genet. 6:623-632. http ://dx .doi .org/10 .1038/nrg1657
158. Snyder-Mackler, N., J. Sanz, J.N. Kohn, J.F. Brinkworth, S. Morrow, A.O. Shaver, J.C. Grenier, R. Pique-Regi, Z.P. Johnson, M.E. Wilson, et al. 2016. Social status alters immune regulation and response to infection in macaques. Science. 354:1041-1045. http ://dx .doi .org/10 .1126/science .aah3580
159. Spielman, R.S., L.A. Bastone, J.T. Burdick, M. Morley, W.J. Ewens, and V.G. Cheung. 2007. Common genetic variants account for differences in gene expression among ethnic groups. Nat. Genet. 39:226-231. http ://dx .doi .org/10 .1038/ng1955
160. Stearns, S.C., S.G. Byars, D.R. Govindaraju, and D. Ewbank. 2010. Measuring selection in contemporary human populations. Nat. Rev. Genet. 11:611-622. http ://dx .doi .org/10 .1038/nrg2831
161. Stranger, B.E., S.B. Montgomery, A.S. Dimas, L. Parts, O. Stegle, C.E. Ingle, M. Sekowska, G.D. Smith, D. Evans, M. Gutierrez-Arcelus, et al. 2012. Patterns of cis regulatory variation in diverse human populations. PLoS Genet. 8:e1002639. http ://dx .doi .org/10 .1371/journal .pgen .1002639
162. Tan, J., Y. Yang, K. Tang, P.C. Sabeti, L. Jin, and S. Wang. 2013. The adaptive variant EDA RV370A is associated with straight hair in East Asians. Hum. Genet. 132:1187-1191. http ://dx .doi .org/10 .1007/s00439-013-1324-1
163. Tennessen, J.A., A.W. Bigham, T.D. O'Connor, W. Fu, E.E. Kenny, S. Gravel, S. McGee, R. Do, X. Liu, G. Jun, et al. NHL BI Exome Sequencing Project. 2012. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science. 337:64-69. http ://dx .doi .org/10 .1126/science .1219240
164. Ter Horst, R., M. Jaeger, S.P. Smeekens, M. Oosting, M.A. Swertz, Y. Li, V. Kumar, D.A. Diavatopoulos, A.F. Jansen, H. Lemmers, et al. 2016. Host and environmental factors influencing individual human cytokine responses. Cell. 167:1111-1124.e13. http ://dx .doi .org/10 .1016/j .cell .2016 .10 .018
165. Tishkoff, S.A., R. Varkonyi, N. Cahinhinan, S. Abbes, G. Argyropoulos, G. Destro-Bisol, A. Drousiotou, B. Dangerfield, G. Lefranc, J. Loiselet, et al. 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science. 293:455-462. http ://dx .doi .org/10 .1126/science .1061573
166. Tishkoff, S.A., F.A. Reed, A. Ranciaro, B.F. Voight, C.C. Babbitt, J.S. Silverman, K. Powell, H.M. Mortensen, J.B. Hirbo, M. Osman, et al. 2007. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39:31-40. http ://dx .doi .org/10 .1038/ng1946
167. Tung, J., L.B. Barreiro, Z.P. Johnson, K.D. Hansen, V. Michopoulos, D. Toufexis, K. Michelini, M.E. Wilson, and Y. Gilad. 2012. Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proc. Natl. Acad. Sci. USA. 109:6490-6495. http ://dx .doi .org/10 .1073/pnas .1202734109
168. Vannberg, F.O., S.J. Chapman, and A.V. Hill. 2011. Human genetic susceptibility to intracellular pathogens. Immunol. Rev. 240:105-116. http ://dx .doi .org/10 .1111/j .1600-065X .2010 .00996 .x
169. Vattathil, S., and J.M. Akey. 2015. Small amounts of archaic admixture provide big insights into human history. Cell. 163:281-284. http ://dx .doi .org/10 .1016/j .cell .2015 .09 .042
170. Veeramah, K.R., and M.F. Hammer. 2014. The impact of whole-genome sequencing on the reconstruction of human population history. Nat. Rev. Genet. 15:149-162. http ://dx .doi .org/10 .1038/nrg3625
171. Vernot, B., and J.M. Akey. 2014. Resurrecting surviving Neandertal lineages from modern human genomes. Science. 343:1017-1021. http ://dx .doi .org/10 .1126/science .1245938
172. Vernot, B., S. Tucci, J. Kelso, J.G. Schraiber, A.B. Wolf, R.M. Gittelman, M. Dannemann, S. Grote, R.C. McCoy, H. Norton, et al. 2016. Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science. 352:235-239. http ://dx .doi .org/10 .1126/science .aad9416
173. Vitti, J.J., S.R. Grossman, and P.C. Sabeti. 2013. Detecting natural selection in genomic data. Annu. Rev. Genet. 47:97-120. http ://dx .doi .org/10 .1146/annurev-genet-111212-133526
174. Voight, B.F., S. Kudaravalli, X. Wen, and J.K. Pritchard. 2006. A map of recent positive selection in the human genome. PLoS Biol. 4:e72. http ://dx .doi .org/10 .1371/journal .pbio .0040072
175. Wang, E.T., G. Kodama, P. Baldi, and R.K. Moyzis. 2006. Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc. Natl. Acad. Sci. USA. 103:135-140. http ://dx .doi .org/10 .1073/pnas .0509691102
176. Yi, X., Y. Liang, E. Huerta-Sanchez, X. Jin, Z.X. Cuo, J.E. Pool, X. Xu, H. Jiang, N. Vinckenbosch, T.S. Korneliussen, et al. 2010. Sequencing of 50 human exomes reveals adaptation to high altitude. Science. 329:75-78. http ://dx .doi .org/10 .1126/science .1190371
177. Zhernakova, A., C.C. Elbers, B. Ferwerda, J. Romanos, G. Trynka, P.C. Dubois, C.G. de Kovel, L. Franke, M. Oosting, D. Barisani, et al. Finnish Celiac Disease Study Group. 2010. Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am. J. Hum. Genet. 86:970-977. http ://dx .doi .org/10 .1016/j .ajhg .2010 .05 .004