A Population Genetic Signal of Polygenic Adaptation

English version České info

The process of adaptation is of fundamental importance in evolutionary biology. Within the last few decades, genotyping technologies and new statistical methods have given evolutionary biologists the ability to identify individual regions of the genome that are likely to have been important in this process. When adaptation occurs in traits that are underwritten by many genes, however, the genetic signals left behind are more diffuse, and no individual region of the genome is likely to show strong signatures of selection. Identifying this signature therefore requires a detailed annotation of sites associated with a particular phenotype. Here we develop and implement a suite of statistical methods to integrate this sort of annotation from genome wide association studies with allele frequency data from many populations, providing a powerful way to identify the signal of adaptation in polygenic traits. We apply our methods to test for the impact of selection on human height, skin pigmentation, body mass index, type 2 diabetes risk, and inflammatory bowel disease risk. We find relatively strong signals for height and skin pigmentation, moderate signals for inflammatory bowel disease, and comparatively little evidence for body mass index and type 2 diabetes risk.

Vyšlo v časopise: A Population Genetic Signal of Polygenic Adaptation. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004412
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004412

Souhrn

Zdroje

1. FisherRA (1918) XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance. Transactions of the Royal Society of Edinburgh 52 : 399–433.

2. Provine WB (2001) The Origins of Theoretical Population Genetics. With a New Afterword. University Of Chicago Press.

3. TurelliM, BartonNH (1990) Dynamics of polygenic characters under selection. Theoretical Population Biology 38 : 1–57.

4. SlateJ (2005) Quantitative trait locus mapping in natural populations: progress, caveats and future directions. Molecular Ecology 14 : 363–379.

5. KingsolverJG, HoekstraHE, HoekstraJM, BerriganD, VignieriSN, et al. (2001) The Strength of Phenotypic Selection in Natural Populations. The American Naturalist 157 : 245–261.

6. HudsonRR, KreitmanM, AguadéM (1987) A test of neutral molecular evolution based on nucleotide data. Genetics 116 : 153–159.

7. McDonaldJH, KreitmanM (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351 : 652–654.

8. BegunDJ, AquadroCF (1992) Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature 356 : 519–520.

9. NielsenR, WilliamsonS, KimY, HubiszMJ, ClarkAG, et al. (2005) Genomic scans for selective sweeps using SNP data. Genome Research 15 : 1566–1575.

10. LattaRG (1998) Differentiation of allelic frequencies at quantitative trait loci affecting locally adaptive traits. American Naturalist 151 : 283–292.

11. LattaRG (2003) Gene flow, adaptive population divergence and comparative population structure across loci. New Phytologist 161 : 51–58.

12. Le CorreV, KremerA (2003) Genetic variability at neutral markers, quantitative trait loci and trait in a subdivided population under selection. Genetics 164 : 1205–1219.

13. Le CorreV, KremerA (2012) The genetic differentiation at quantitative trait loci under local adaptation. Molecular Ecology 21 : 1548–1566.

14. KremerA, Le CorreV (2011) Decoupling of differentiation between traits and their underlying genes in response to divergent selection. Heredity 108 : 375–385.

15. PritchardJK, PickrellJK, CoopG (2010) The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Current Biology 20: R208–15.

16. KemperKE, SaxtonSJ, BolormaaS, HayesBJ, GoddardME (2014) Selection for complex traits leaves little or no classic signatures of selection. BMC Genomics 15 : 1–14.

17. RischN, MerikangasK (1996) The future of genetic studies of complex human diseases. Science 273 : 1516–1517.

18. VisscherPM, BrownMA, McCarthyMI, YangJ (2012) Five Years of GWAS Discovery. The American Journal of Human Genetics 90 : 7–24.

19. AtwellS, HuangYS, Vilhj a lmssonBJ, WillemsG, HortonM, et al. (2010) Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature 465 : 627–631.

20. Fournier-LevelA, KorteA, CooperMD, NordborgM, SchmittJ, et al. (2011) A Map of Local Adaptation in Arabidopsis thaliana. Science 334 : 86–89.

21. MackayTFC, RichardsS, StoneEA, BarbadillaA, AyrolesJF, et al. (2012) The Drosophila melanogaster Genetic Reference Panel. Nature 482 : 173–178.

22. ManolioTA, CollinsFS, CoxNJ, GoldsteinDB, HindorffLA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461 : 747–753.

23. BloomJS, EhrenreichIM, LooWT, LiteTLV, KruglyakL (2013) Finding the sources of missing heritability in a yeast cross. Nature 494 : 234–237.

24. MylesS, DavisonD, BarrettJ, StonekingM, TimpsonN (2008) Worldwide population differentiation at disease-associated SNPs. BMC medical genomics 1 : 22.

25. CastoAM, FeldmanMW (2011) Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations? PLoS Genetics 7: e1001266.

26. JostinsL, RipkeS, WeersmaRK, DuerrRH, McGovernDP, et al. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491 : 119–124.

27. ZhangG, MugliaLJ, ChakrabortyR, AkeyJM (2013) Signatures of natural selection on genetic variants affecting complex human traits. Applied & Translational Genomics 2 : 77–93.

28. TurchinMC, ChiangCW, PalmerCD, SankararamanS, ReichD, et al. (2012) Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nature Genetics 44 : 1015–1019.

29. FraserHB (2013) Gene expression drives local adaptation in humans. Genome Research 23 : 1089–1096.

30. CoronaE, ChenR, SikoraM, MorganAA, PatelCJ, et al. (2013) Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration. PLoS Genetics 9: e1003447.

31. Fisher R (1930) The Genetical Theory of Natural Selection. Clarendon Press.

32. Falconer D (1960) Introduction to Quantitative Genetics. Ronald Press.

33. ProutT, BarkerF (1993) F Statistics in Drosophila buzzatii: Selection, Population Size and Inbreed. Genetics 375 : 369–375.

34. SpitzeK (1993) Population structure in Daphnia obtusa: quantitative genetic and allozymic variation. Genetics 135 : 367–374.

35. LewontinRC, KrakauerJ (1973) Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. Genetics 74 : 175–195.

36. NeiM, MaruyamaT (1975) Lewontin-Krakauertest for neutral genes. Genetics 80 : 395.

37. Robertson A (1975) GENE FREQUENCY DISTRIBUTIONS AS A TEST OF SELECTIVE NEUTRALITY. Genetics.

38. Bonhomme M, Chevalet C, Servin B, Boitard S, Abdallah JM, et al.. (2010) Detecting Selection in Population Trees: The Lewontin and Krakauer Test Extended. Genetics.

39. Günther T, Coop G (2013) Robust Identification of Local Adaptation from Allele Frequencies. Genetics.

40. OvaskainenO, KarhunenM, ZhengC, AriasJMC, MeriläJ (2011) A New Method to Uncover Signatures of Divergent and Stabilizing Selection in Quantitative Traits. Genetics 189 : 621–632.

41. KarhunenM, OvaskainenO, HerczegG, MERILÄJ (2014) bringing habitat information into statistical tests of local adaptation in quantitative traits: a case study of nine-spined sticklebacks. Evolution 68 : 559–568.

42. NicholsonG, SmithAV, JonssonF, GustafssonO, StefanssonK, et al. (2002) Assessing population differentiation and isolation from single-nucleotide polymorphism data. Journal of the Royal Statistical Society: Series B (Statistical Methodology) 64 : 695–715.

43. WEIRBS, HILLWG (2002) Estimating F-statistics. Annual review of genetics 36 : 721–750.

44. Cavalli-SforzaLL, BarraiI, EdwardsAWF (1964) Analysis of Human Evolution Under Random Genetic Drift. Cold Spring Harbor Symposia on Quantitative Biology 29 : 9–20.

45. FelsensteinJ (1982) How can we infer geography and history from gene frequencies? Journal of Theoretical Biology 96 : 9–20.

46. PickrellJK, PritchardJK (2012) Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data. PLoS Genetics 8: e1002967.

47. CoopG, WitonskyD, Di RienzoA, PritchardJK (2010) Using environmental correlations to identify loci underlying local adaptation. Genetics 185 : 1411–1423.

48. FarielloMI, BoitardS, NayaH, SanCristobalM, ServinB (2013) Detecting Signatures of Selection Through Haplotype Differentiation Among Hierarchically Structured Populations. Genetics 193 : 929–941.

49. Guillot G (2012) Detection of correlation between genotypes and environmental variables. A fast computational approach for genomewide studies. arXiv preprint arXiv:12060889.

50. Bradburd GS, Ralph PL, Coop GM (2013) Disentangling the effects of geographic and ecological isolation on genetic differentiation. arXiv preprint arXiv:13023274.

51. Rao C, Toutenburg H (1999) Linear Models: Least Squares and Alternatives, Springer. 2nd edition, pp. 104–106.

52. WrightS (1951) The Genetical Structure of Populations. Annals of Eugenics 15 : 323–354.

53. LandeR (1992) Neutral theory of quantitative genetic variance in an island model with local extinction and colonization. Evolution 46 : 381–389.

54. WhitlockMC (1999) Neutral additive genetic variance in a metapopulation. Genetical Research 74 : 215–221.

55. RogersAR, HarpendingHC (1983) Population structure and quantitative characters. Genetics 105 : 985–1002.

56. WhitlockMC (2008) Evolutionary inference from QST. Molecular Ecology 17 : 1885–1896.

57. WhitlockMC, GuillaumeF (2009) Testing for Spatially Divergent Selection: Comparing QST to FST. Genetics 183 : 1055–1063.

58. LiJZ, AbsherDM, TangH, SouthwickAM, CastoAM, et al. (2008) Worldwide human relationships inferred from genome-wide patterns of variation. Science (New York, NY) 319 : 1100–1104.

59. PickrellJK, CoopG, NovembreJ, KudaravalliS, LiJZ, et al. (2009) Signals of recent positive selection in a worldwide sample of human populations. Genome Research 19 : 826–837.

60. CharlesworthB, NordborgM, CharlesworthD (1997) The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations. Genetics Research 70 : 155–174.

61. McVickerG, GordonD, DavisC, GreenP (2009) Widespread Genomic Signatures of Natural Selection in Hominid Evolution. PLoS Genetics 5: e1000471.

62. RosenbergNA, PritchardJK, WeberJL, CannHM, KiddKK, et al. (2002) Genetic structure of human populations. Science (New York, NY) 298 : 2381–2385.

63. HancockAM, WitonskyDB, GordonAS, EshelG, PritchardJK, et al. (2008) Adaptations to Climate in Candidate Genes for Common Metabolic Disorders. PLoS Genetics 4: e32.

64. Lango AllenH, EstradaK, LettreG, BerndtSI, WeedonMN, et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467 : 832–838.

65. ZaitlenN, KraftP, PattersonN, PasaniucB, BhatiaG, et al. (2013) Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits. PLoS Genetics 9: e1003520.

66. GustafssonA, LindenforsP (2009) Latitudinal patterns in human stature and sexual stature dimorphism. Annals of Human Biology 36 : 74–87.

67. BelezaS, JohnsonNa, CandilleSI, AbsherDM, CoramMA, et al. (2013) Genetic architecture of skin and eye color in an african-European admixed population. PLoS Genetics 9: e1003372.

68. JablonskiNG, ChaplinG (2000) The evolution of human skin coloration. Journal of Human Evolution 39 : 57–106.

69. LaoO, de GruijterJM, van DuijnK, NavarroA, KayserM (2007) Signatures of Positive Selection in Genes Associated with Human Skin Pigmentation as Revealed from Analyses of Single Nucleotide Polymorphisms. Annals of Human Genetics 71 : 354–369.

70. JablonskiNG, ChaplinG (2010) Colloquium Paper: Human skin pigmentation as an adaptation to UV radiation. Proceedings of the National Academy of Sciences of the United States of America 107 : 8962–8968.

71. NortonHL, KittlesRA, ParraE, McKeigueP, MaoX, et al. (2006) Genetic Evidence for the Convergent Evolution of Light Skin in Europeans and East Asians. Molecular Biology and Evolution 24 : 710–722.

72. MillerCT, BelezaS, PollenAA, SchluterD, KittlesRA, et al. (2007) cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans. Cell 131 : 1179–1189.

73. EdwardsM, BighamA, TanJ, LiS, GozdzikA, et al. (2010) Association of the OCA2 Polymorphism His615Arg with Melanin Content in East Asian Populations: Further Evidence of Convergent Evolution of Skin Pigmentation. PLoS Genetics 6: e1000867.

74. SpeliotesEK, WillerCJ, BerndtSI, MondaKL, ThorleifssonG, et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics 42 : 937–948.

75. MorrisAP, VoightBF, TeslovichTM, FerreiraT, SegrèAV, et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Publishing Group 44 : 981–990.

76. HelgasonA, PálssonS, ThorleifssonG, GrantSFA, EmilssonV, et al. (2007) Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nature Genetics 39 : 218–225.

77. HancockAM, WitonskyDB, EhlerE, Alkorta-AranburuG, BeallC, et al. (2010) Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proceedings of the National Academy of Sciences 107 : 8924–8930.

78. KlimentidisYC, AbramsM, WangJ, FernandezJR, AllisonDB (2011) Natural selection at genomic regions associated with obesity and type-2 diabetes: East Asians and sub-Saharan Africans exhibit high levels of differentiation at type-2 diabetes regions. Human Genetics 129 : 407–418.

79. NeelJV (1962) Diabetes Mellitus: A “Thrifty” Genotype Rendered Detrimental by “Progress”? American journal of human genetics 14 : 353.

80. FreedmanML, ReichD, PenneyKL, McDonaldGJ, MignaultAA, et al. (2004) Assessing the impact of population stratification on genetic association studies. Nature Genetics 36 : 388–393.

81. CampbellCD, OgburnEL, LunettaKL, LyonHN, FreedmanML, et al. (2005) Demonstrating stratification in a European American population. Nature Genetics 37 : 868–872.

82. PriceAL, PattersonNJ, PlengeRM, WeinblattME, ShadickNA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38 : 904–909.

83. KangHM, ZaitlenNA, WadeCM, KirbyA, HeckermanD, et al. (2008) Efficient Control of Population Structure in Model Organism Association Mapping. Genetics 178 : 1709–1723.

84. PriceAL, ZaitlenNA, ReichD, PattersonN (2010) New approaches to population stratification in genome-wide association studies. Nature Publishing Group 11 : 459–463.

85. DiaoL, ChenKC (2012) Local Ancestry Corrects for Population Structure in Saccharomyces cerevisiae Genome-Wide Association Studies. Genetics 192 : 1503–1511.

86. LiuL, ZhangD, LiuH, ArendtC (2013) Robust methods for population stratification in genome wide association studies. BMC bioinformatics 14 : 132.

87. ChoYS, GoMJ, KimYJ, HeoJY, OhJH, et al. (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nature Genetics 41 : 527–534.

88. ChoYS, ChenCH, HuC, LongJ, OngRTH, et al. (2011) Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nature Publishing Group 44 : 67–72.

89. VoightBF, ScottLJ, SteinthorsdottirV, MorrisAP, DinaC, et al. (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Publishing Group 42 : 579–589.

90. KoonerJS, SaleheenD, SimX, SehmiJ, ZhangW, et al. (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nature Publishing Group 43 : 984–989.

91. N'Diaye A, Chen GK, Palmer CD, Ge B, Tayo B (2011) PLOS Genetics: Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry. PLoS Genetics.

92. CartyCL, JohnsonNa, HutterCM, ReinerAP, PetersU, et al. (2012) Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe). Human Molecular Genetics 21 : 711–720.

93. MondaKL, ChenGK, TaylorKC, PalmerC, EdwardsTL, et al. (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nature Genetics 45 : 690–696.

94. CarlsonCS, MatiseTC, NorthKE, HaimanCA, FesinmeyerMD, et al. (2013) Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study. PLoS Biology 11: e1001661.

95. MarigortaUM, NavarroA (2013) High Trans-ethnic Replicability of GWAS Results Implies Common Causal Variants. PLoS Genetics 9: e1003566.

96. KangHM, SulJH (2010) Service SK, Zaitlen NA, Kong Sy, et al (2010) technical reports. Nature Genetics 42 : 348–354.

97. ZhouX, StephensM (2012) technical reports. Nature Genetics 44 : 821–824.

98. Liu X, Ong RTH, Pillai EN, Elzein AM, Small KS, et al.. (2013) Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations. American journal of human genetics: 1–16.

99. Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, et al.. (2007) Genome-wide detection and characterization of positive selection in human populations:Article: Nature. Nature.

100. WilliamsonSH, HubiszMJ, ClarkAG, PayseurBA, BustamanteCD, et al. (2007) Localizing Recent Adaptive Evolution in the Human Genome. PLoS Genetics 3: e90.

101. SturmRa (2009) Molecular genetics of human pigmentation diversity. Human Molecular Genetics 18: R9–17.

102. FrancoM, BilalU, OrdunezP, BenetM, MorejonA, et al. (2013) Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980–2010: repeated cross sectional surveys and ecological comparison of secular trends. BMJ 346: f1515–f1515.

103. KaweckiTJ, EbertD (2004) Conceptual issues in local adaptation. Ecology Letters 7 : 1225–1241.

104. WadeMJ (2002) A gene's eye view of epistasis, selection and speciation. Journal of Evolutionary Biology 15 : 337–346.

105. ConoverDO, SchultzET (1995) Phenotypic similarity and the evolutionary significance of countergradient variation. Trends in Ecology & Evolution 10 : 248–252.

106. ZhangXS, HILLWG (2008) The Anomalous Effects of Biased Mutation Revisited: Mean-Optimum Deviation and Apparent Directional Selection Under Stabilizing Selection. Genetics 179 : 1135–1141.

107. MeuwissenTH, HayesBJ, GoddardME (2001) Prediction of total genetic value using genome-wide dense marker maps. Genetics 157 : 1819–1829.

108. HayesBJ, BowmanPJ, ChamberlainAJ, GoddardME (2009) Invited review. Journal of Dairy Science 92 : 433–443.

109. MeuwissenT, HayesB, GoddardM (2013) Accelerating Improvement of Livestock with Genomic Selection. Annual Review of Animal Biosciences 1 : 221–237.

110. ZhouX, CarbonettoP, StephensM (2013) Polygenic modeling with bayesian sparse linear mixed models. PLoS Genetics 9: e1003264.

111. YangJ, BenyaminB, McEvoyBP, GordonS, HendersAK, et al. (2010) Common SNPs explain a large proportion of the heritability for human height. Nature Genetics 42 : 565–569.

112. DaviesG, TenesaA, PaytonA, YangJ, HarrisSE, et al. (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16 : 996–1005.

113. YangJ, ManolioTA, PasqualeLR, BoerwinkleE, CaporasoN, et al. (2011) ng.823. Nature Publishing Group 43 : 519–525.

114. LeeSH, DeCandiaTR, RipkeS, YangJ, SullivanPF, et al. (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nature Genetics 44 : 247–250.

115. de los CamposG, GianolaD, AllisonDB (2010) PersPectives. Nature Publishing Group 11 : 880–886.

116. de los CamposG, KlimentidisYC, VazquezAI, AllisonDB (2012) Prediction of Expected Years of Life Using Whole-Genome Markers. PLoS ONE 7: e40964.

117. de los CamposG, VazquezAI, FernandoR, KlimentidisYC, SorensenD (2013) Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor. PLoS Genetics 9: e1003608.

118. KarhunenM, OvaskainenO (2012) Estimating Population-Level Coancestry Coefficients by an Admixture F Model. Genetics 192 : 609–617.

119. Global Lipids GeneticsConsortium, WillerCJ, SchmidtEM, SenguptaS, PelosoGM, et al. (2013) Discovery and refinement of loci associated with lipid levels. Nature Genetics 45 : 1274–1283.

120. KremerA, ZanettoA, DucoussoA (1997) Multilocus and multitrait measures of differentiation for gene markers and phenotypic traits. Genetics 145 : 1229–1241.

121. BlowsMW (2007) A tale of two matrices: multivariate approaches in evolutionary biology. Journal of Evolutionary Biology 20 : 1–8.

122. ChenowethSF, BlowsMW (2008) Q(St) meets the G matrix: the dimensionality of adaptive divergence in multiple correlated quantitative traits. Evolution; international journal of organic evolution 62 : 1437–1449.

123. Falconer DS (1952) The problem of environment and selection. American Naturalist: 293–298.

124. ConradDF, JakobssonM, CoopG, WenX, WallJD, et al. (2006) A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nature Genetics 38 : 1251–1260.

125. ScheetP, StephensM (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. American journal of human genetics 78 : 629–644.

126. ReichD, PattersonN (2005) Will admixture mapping work to find disease genes? Philosophical transactions of the Royal Society of London Series B, Biological sciences 360 : 1605–1607.

127. GustafssonA, LindenforsP (2004) Human size evolution: no evolutionary allometric relationship between male and female stature. Journal of Human Evolution 47 : 253–266.

128. ParraEJ, KittlesRA, ShriverMD (2004) Implications of correlations between skin color and genetic ancestry for biomedical research. Nature Genetics 36: S54–S60.