What do we call the gradual change in frequency of a genotypes and phenotypes over geographic space?

1. Cavalli-Sforza LL, Menozzi P, Piazza A. History and geography of human genes. Princeton University Press; Princeton, N.J: 1994. [Google Scholar]

2. Roychoudhury AK, Nei M. Human Polymorphic Genes World Distribution. Oxford University Press; New York - Oxford: 1988. [Google Scholar]

3. Haldane JBS. The rate of mutation of human genes. Hereditas. 1949;35 (Suppl 1):267–272. [Google Scholar]

4. Fisher R. The wave of advance of advantageous genes. Ann Eugen. 1937;7:355–369. [Google Scholar]

5. Roberts DF. Human pigmentation: its geographical and racial distribution and biological significance. J Soc Cosmetic Chem. 1977;28:329–342. [Google Scholar]

6. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biologic and cultural interrelations. II. A culture historical hypothesis. Am J Dig Dis. 1970;15:695–710. [PubMed] [Google Scholar]

7. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. I. Review of the medical research. Am J Dig Dis. 1969;14:819–36. [PubMed] [Google Scholar]

8. Cavalli-Sforza LL. Analytic review: some current problems of human population genetics. Am J Hum Genet. 1973;25:82–104. [PMC free article] [PubMed] [Google Scholar]

9. Katzmarzyk PT, Leonard WR. Climatic influences on human body size and proportions: ecological adaptations and secular trends. Am J Phys Anthropol. 1998;106:483–503. [PubMed] [Google Scholar]

10. Roberts DF. Climate and Human Variability. Cummings; Menlo Park: 1978. [Google Scholar]

11. Friedlaender JS, et al. The genetic structure of Pacific Islanders. PLoS Genet. 2008;4:e19. [PMC free article] [PubMed] [Google Scholar]

12. Wang S, et al. Genetic variation and population structure in native Americans. PLoS Genet. 2007;3:e185. [PMC free article] [PubMed] [Google Scholar]

13. Nelson MR, et al. The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research. Am J Hum Genet. 2008;83:347–58. [PMC free article] [PubMed] [Google Scholar]

14. Novembre J, et al. Genes mirror geography within Europe. Nature. 2008;456:98–101. [PMC free article] [PubMed] [Google Scholar]

15. Lao O, et al. Correlation between genetic and geographic structure in Europe. Curr Biol. 2008;18:1241–8. [PubMed] [Google Scholar]

16. Tishkoff SA, et al. The genetic structure and history of Africans and African Americans. Science. 2009;324:1035–44. [PMC free article] [PubMed] [Google Scholar]

17. Li JZ, et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science. 2008;319:1100–4. [PubMed] [Google Scholar]

18. Rosenberg NA, et al. Genetic structure of human populations. Science. 2002;298:2381–5. [PubMed] [Google Scholar]

19. Jakobsson M, et al. Genotype, haplotype and copy-number variation in worldwide human populations. Nature. 2008;451:998–1003. [PubMed] [Google Scholar]

20. Rosenberg NA, et al. Clines, clusters, and the effect of study design on the inference of human population structure. PLoS Genet. 2005;1:e70. [PMC free article] [PubMed] [Google Scholar]

21. Ramachandran S, et al. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc Natl Acad Sci U S A. 2005;102:15942–7. [PMC free article] [PubMed] [Google Scholar]

22. Serre D, Paabo S. Evidence for gradients of human genetic diversity within and among continents. Genome Res. 2004;14:1679–85. [PMC free article] [PubMed] [Google Scholar]

23. Handley LJ, Manica A, Goudet J, Balloux F. Going the distance: human population genetics in a clinal world. Trends Genet. 2007;23:432–9. [PubMed] [Google Scholar]

24. Prugnolle F, Manica A, Balloux F. Geography predicts neutral genetic diversity of human populations. Curr Biol. 2005;15:R159–60. [PMC free article] [PubMed] [Google Scholar]

25. Edmonds CA, Lillie AS, Cavalli-Sforza LL. Mutations arising in the wave front of an expanding population. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:975–979. [PMC free article] [PubMed] [Google Scholar]

26. Vlad MO, Cavalli-Sforza LL, Ross J. Enhanced (hydrodynamic) transport induced by population growth in reaction-diffusion systems with application to population genetics. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:10249–10253. [PMC free article] [PubMed] [Google Scholar]

27. Klopfstein S, Currat M, Excoffier L. The fate of mutations surfing on the wave of a range expansion. Molecular Biology and Evolution. 2006;23:482–490. [PubMed] [Google Scholar]

28. Excoffier L, Ray N. Surfing during population expansions promotes genetic revolutions and structuration. Trends in Ecology & Evolution. 2008;23:347–351. [PubMed] [Google Scholar]

29. Currat M, et al. Comment on “Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens” and “Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans” Science. 2006;313:172. author reply 172. [PubMed] [Google Scholar]

30. Hofer T, Ray N, Wegmann D, Excoffier L. Large Allele Frequency Differences between Human Continental Groups are more Likely to have Occurred by Drift During range Expansions than by Selection. Annals of Human Genetics. 2009;73:95–108. [PubMed] [Google Scholar]

31. Wright S. The Genetical Structure of Populations. Annals of Eugenics. 1951;15:323–354. [PubMed] [Google Scholar]

32. Holsinger KE, Weir BS. Genetics in geographically structured populations: defining, estimating and interpreting F(ST) Nat Rev Genet. 2009;10:639–50. [PMC free article] [PubMed] [Google Scholar]

33. Lewontin RC, Krakauer J. Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. Genetics. 1973;74:175–95. [PMC free article] [PubMed] [Google Scholar]

34. Haldane JB. The theory of a cline. J Genet. 1948;48:277–84. [PubMed] [Google Scholar]

35. Cavalli-Sforza LL. Population structure and human evolution. Proc R Soc Lond B Biol Sci. 1966;164:362–79. [PubMed] [Google Scholar]

36. Bowcock AM, et al. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc Natl Acad Sci U S A. 1991;88:839–43. [PMC free article] [PubMed] [Google Scholar]

37. Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 2002;12:1805–14. [PMC free article] [PubMed] [Google Scholar]

38. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet. 2008;40:340–5. [PubMed] [Google Scholar]

39. Coop G, et al. The role of geography in human adaptation. PLoS Genet. 2009;5:e1000500. [PMC free article] [PubMed] [Google Scholar]

40. Beaumont MA, Balding DJ. Identifying adaptive genetic divergence among populations from genome scans. Mol Ecol. 2004;13:969–80. [PubMed] [Google Scholar]

41. Beaumont MA, Nichols RA. Evaluating loci for use in the genetic analysis of population structure. Proc R Soc Lond B Biol Sci. 1996;263:1719–1626. [Google Scholar]

42. Excoffier L, Hofer T, Foll M. Detecting loci under selection in a hierarchically structured population. Heredity. 2009 [PubMed] [Google Scholar]

43. Lamason RL, et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science. 2005;310:1782–6. [PubMed] [Google Scholar]

44. Williamson SH, et al. Localizing recent adaptive evolution in the human genome. PLoS Genet. 2007;3:e90. [PMC free article] [PubMed] [Google Scholar]

45. Charlesworth B, Nordborg M, Charlesworth D. The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations. Genet Res. 1997;70:155–74. [PubMed] [Google Scholar]

46. Hu XS, He F. Background selection and population differentiation. J Theor Biol. 2005;235:207–19. [PubMed] [Google Scholar]

47. Santiago E, Caballero A. Variation after a selective sweep in a subdivided population. Genetics. 2005;169:475–83. [PMC free article] [PubMed] [Google Scholar]

48. Berry A, Kreitman M. Molecular analysis of an allozyme cline: alcohol dehydrogenase in Drosophila melanogaster on the east coast of North America. Genetics. 1993;134:869–93. [PMC free article] [PubMed] [Google Scholar]

49. Umina PA, Weeks AR, Kearney MR, McKechnie SW, Hoffmann AA. A rapid shift in a classic clinal pattern in Drosophila reflecting climate change. Science. 2005;308:691–3. [PubMed] [Google Scholar]

50. Joost S, et al. A spatial analysis method (SAM) to detect candidate loci for selection: towards a landscape genomics approach to adaptation. Mol Ecol. 2007;16:3955–69. [PubMed] [Google Scholar]

51. Hancock AM, et al. Adaptations to climate in candidate genes for common metabolic disorders. PLoS Genet. 2008;4:e32. [PMC free article] [PubMed] [Google Scholar]

52. Thompson EE, et al. CYP3A variation and the evolution of salt-sensitivity variants. Am J Hum Genet. 2004;75:1059–69. [PMC free article] [PubMed] [Google Scholar]

53. Young JH, et al. Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion. PLoS Genet. 2005;1:e82. [PMC free article] [PubMed] [Google Scholar]

54. Schlotterer C. A microsatellite-based multilocus screen for the identification of local selective sweeps. Genetics. 2002;160:753–63. [PMC free article] [PubMed] [Google Scholar]

55. Kauer MO, Dieringer D, Schlotterer C. A microsatellite variability screen for positive selection associated with the “out of Africa” habitat expansion of Drosophila melanogaster. Genetics. 2003;165:1137–48. [PMC free article] [PubMed] [Google Scholar]

56. Storz JF, Payseur BA, Nachman MW. Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa. Mol Biol Evol. 2004;21:1800–11. [PubMed] [Google Scholar]

57. Marshall JM, Weiss RE. A Bayesian heterogeneous analysis of variance approach to inferring recent selective sweeps. Genetics. 2006;173:2357–70. [PMC free article] [PubMed] [Google Scholar]

58. Sabeti PC, et al. Genome-wide detection and characterization of positive selection in human populations. Nature. 2007;449:913–8. [PMC free article] [PubMed] [Google Scholar]

59. Tang K, Thornton KR, Stoneking M. A new approach for using genome scans to detect recent positive selection in the human genome. PLoS Biol. 2007;5:e171. [PMC free article] [PubMed] [Google Scholar]

60. Voight BF, Kudaravalli S, Wen X, Pritchard JK. A map of recent positive selection in the human genome. PLoS Biol. 2006;4:e72. [PMC free article] [PubMed] [Google Scholar]

61. Bersaglieri T, et al. Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet. 2004;74:1111–20. [PMC free article] [PubMed] [Google Scholar]

62. Novembre J, Galvani AP, Slatkin M. The geographic spread of the CCR5 Delta32 HIV-resistance allele. PLoS Biol. 2005;3:e339. [PMC free article] [PubMed] [Google Scholar]

63. Sabeti PC, et al. The case for selection at CCR5-Delta32. PLoS Biol. 2005;3:e378. [PMC free article] [PubMed] [Google Scholar]

64. Endler JA. Geographic variation, speciation, and clines. Princeton University Press; Princeton, N.J: 1977. [PubMed] [Google Scholar]

65. Enattah NS, et al. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30:233–7. [PubMed] [Google Scholar]

66. Tishkoff SA, et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007;39:31–40. [PMC free article] [PubMed] [Google Scholar]

67. Enattah NS, et al. Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture. Am J Hum Genet. 2008;82:57–72. [PMC free article] [PubMed] [Google Scholar]

68. Norton HL, et al. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol Biol Evol. 2007;24:710–22. [PubMed] [Google Scholar]

69. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371:64–74. [PubMed] [Google Scholar]

70. Flint J, Harding RM, Boyce AJ, Clegg JB. The population genetics of the haemoglobinopathies. Baillieres Clin Haematol. 1998;11:1–51. [PubMed] [Google Scholar]

71. Hill AV. Molecular epidemiology of the thalassaemias (including haemoglobin E) Baillieres Clin Haematol. 1992;5:209–38. [PubMed] [Google Scholar]

72. Goldstein DB, Holsinger KE. Maintenance of Polygenic Variation in Spatially Structured Populations - Roles for Local Mating and Genetic Redundancy. Evolution. 1992;46:412–429. [PubMed] [Google Scholar]

73. Kelly JK. Geographical variation in selection, from phenotypes to molecules. American Naturalist. 2006;167:481–495. [PubMed] [Google Scholar]

74. Latta RG. Differentiation of allelic frequencies at quantitative trait loci affecting locally adaptive traits. American Naturalist. 1998;151:283–292. [PubMed] [Google Scholar]

75. Pickrell JK, et al. Signals of recent positive selection in a worldwide sample of human populations. Genome Res. 2009;19:826–37. [PMC free article] [PubMed] [Google Scholar]

76. Myles S, Somel M, Tang K, Kelso J, Stoneking M. Identifying genes underlying skin pigmentation differences among human populations. Human Genetics. 2007;120:613–621. [PubMed] [Google Scholar]

77. Norton HL, et al. Genetic evidence for the convergent evolution of light skin in Europeans and east Asians. Molecular Biology and Evolution. 2007;24:710–722. [PubMed] [Google Scholar]

78. Przeworski M, Coop G, Wall JD. The signature of positive selection on standing genetic variation. Evolution. 2005;59:2312–23. [PubMed] [Google Scholar]

79. Hermisson J, Pennings PS. Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics. 2005;169:2335–52. [PMC free article] [PubMed] [Google Scholar]

80. Nagylaki T, Lou Y. Evolution under multiallelic migration-selection models. Theoretical Population Biology. 2007;72:21–40. [PubMed] [Google Scholar]

81. Prugnolle F, et al. Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol. 2005;15:1022–7. [PubMed] [Google Scholar]

82. Harding RM, et al. Evidence for variable selective pressures at MC1R. Am J Hum Genet. 2000;66:1351–61. [PMC free article] [PubMed] [Google Scholar]

83. Romeo S, et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet. 2007;39:513–6. [PMC free article] [PubMed] [Google Scholar]

84. Luca F, et al. Multiple advantageous amino acid variants in the NAT2 gene in human populations. PLoS One. 2008;3:e3136. [PMC free article] [PubMed] [Google Scholar]

85. Patin E, et al. Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes. Am J Hum Genet. 2006;78:423–36. [PMC free article] [PubMed] [Google Scholar]

86. Perry GH, et al. Diet and the evolution of human amylase gene copy number variation. Nat Genet. 2007;39:1256–60. [PMC free article] [PubMed] [Google Scholar]

87. Slatkin M, Wiehe T. Genetic hitch-hiking in a subdivided population. Genet Res. 1998;71:155–60. [PubMed] [Google Scholar]

88. Levene H. Genetic Equilibrium When More Than One Ecological Niche Is Available. American Naturalist. 1953;87:331–333. [Google Scholar]

89. Hoekstra RF, Bijlsma R, Dolman AJ. Polymorphism from Environmental Heterogeneity - Models Are Only Robust If the Heterozygote Is Close in Fitness to the Favored Homozygote in Each Environment. Genetical Research. 1985;45:299–314. [PubMed] [Google Scholar]

90. Smith JM, Hoekstra R. Polymorphism in a Varied Environment - How Robust Are the Models. Genetical Research. 1980;35:45–57. [PubMed] [Google Scholar]

91. Barton NaC, AG . In: Population Biology: Ecological and Evolutionary Viewpoints. Wohrmann KaJ, SK, editors. Springer-Verlag; Berlin: 1990. [Google Scholar]

92. Fisher RA. Gene Frequencies in a Cline Determined by Selection and Diffusion. Biometrics. 1950;6:353–361. [PubMed] [Google Scholar]

93. Slatkin M. Gene Flow and Selection in a Cline. Genetics. 1973;75:733–756. [PMC free article] [PubMed] [Google Scholar]

94. Slatkin M. Gene Flow and Selection in a 2-Locus System. Genetics. 1975;81:787–802. [PMC free article] [PubMed] [Google Scholar]

95. May RM, Endler JA, Mcmurtrie RE. Gene Frequency Clines in Presence of Selection Opposed by Gene Flow. American Naturalist. 1975;109:659–676. [PubMed] [Google Scholar]

96. Nagylaki T. Conditions for Existence of Clines. Genetics. 1975;80:595–615. [PMC free article] [PubMed] [Google Scholar]

97. Nagylaki T. Clines with Variable Migration. Genetics. 1976;83:867–886. [PMC free article] [PubMed] [Google Scholar]

98. Nagylaki T. Clines with Asymmetric Migration. Genetics. 1978;88:813–827. [PMC free article] [PubMed] [Google Scholar]

99. Endler JA. Gene Flow and Population Differentiation. Science. 1973;179:243–250. [PubMed] [Google Scholar]

100. Slatkin M, Maruyama T. Genetic Drift in a Cline. Genetics. 1975;81:209–222. [PMC free article] [PubMed] [Google Scholar]

101. Gleibermann L. Blood pressure and dietary salt in human populations. Ecol Food Nutr. 1973;2:143–156. [Google Scholar]

102. Beckman G, et al. Is p53 polymorphism maintained by natural selection? Hum Hered. 1994;44:266–70. [PubMed] [Google Scholar]

103. Shi H, et al. Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia. Am J Hum Genet. 2009;84:534–41. [PMC free article] [PubMed] [Google Scholar]

104. Luca F, et al. Adaptive variation regulates the expression of the human SGK1 gene in response to stress. PLoS Genet. 2009;5:e1000489. [PMC free article] [PubMed] [Google Scholar]

105. Teshima KM, Coop G, Przeworski M. How reliable are empirical genomic scans for selective sweeps? Genome Res. 2006;16:702–12. [PMC free article] [PubMed] [Google Scholar]

Page 2

The “wave of advance” spread of a globally advantageous mutation

Arrows indicate how the allele frequencies of a selected allele (red) are expected to change over time, depending on the pattern of selective advantage of the allele (indicated in green above each plot). Vertical arrows represent the magnitude of increase expected due to selection. Horizontal arrows represent how dispersal homogenizes allele frequencies across space. For every selected allele, a representative neutral allele (blue) of similar average frequency is shown for comparison. In each case the allele is supposed to have arisen at location 3 along the x-axis (marked with a vertical dashed line); the spread will continue until the selected allele is at frequency 1 across the whole habitat.

(A) Uniform selective advantage across space. If the novel variant is identically advantageous everywhere, the prediction is that as the variant increases in frequency it will be exceptionally concentrated around its geographic origin relative to a neutral variant of the same age. One effect of this is to create transiently enhanced levels of divergence among populations and clines in allele frequencies that reflect the geographic origin of the allele.

(B, C) Non-uniform advantage across space. In scenario B, the novel allele is introduced to the regions in which it is most advantageous and increase in frequency rapidly in those regions. This can lead to transient correlations between allele frequency and the environmental factor that drives positive selection. In contrast, in scenario C, the novel allele arises in an area distant from where it is most advantageous. It will increase in frequency locally before spreading outwards, and its distribution will carry a strong signature of its geographic origin and be less reflective of spatial variation in selective advantage.

These models assume selection acting on new mutations, which may not be the prevailing model in humans. Selection on pre-existing variation will complicate these simple scenarios.