Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Recent and ongoing selection in the human genome

Nature Reviews Genetics volume 8, pages 857–868 (2007)Cite this article

Key Points

  • Genes or genomic regions that are under selection will typically be functionally important and will often be disease associated. They are, therefore, of interest not only to evolutionary biologists, but also to researchers in the fields of functional genomics and disease genetics.

  • Both negative selection acting against deleterious mutations and positive selection acting in favour of beneficial mutations is common in the human genome.

  • Although most selection acting on segregating mutations in disease genes is negative selection — acting against deleterious, predominantly recessive mutations — some mutations in complex diseases might also have been affected by positive selection in the past or present.

  • Several genome-wide scans for loci that are under selection have been carried out. These scans have provided a large amount of new information, but have also generated controversy as the concordance between results is not always high.

  • The main reason for the lack of concordance is probably that different tests differ in their power to detect different forms of selection. However, statistical problems relating to assumptions about demography, recombination and ascertainment biases can also affect the results of some studies.

Abstract

The recent availability of genome-scale genotyping data has led to the identification of regions of the human genome that seem to have been targeted by selection. These findings have increased our understanding of the evolutionary forces that affect the human genome, have augmented our knowledge of gene function and promise to increase our understanding of the genetic basis of disease. However, inferences of selection are challenged by several confounding factors, especially the complex demographic history of human populations, and concordance between studies is variable. Although such studies will always be associated with some uncertainty, steps can be taken to minimize the effects of confounding factors and improve our interpretation of their findings.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Selective sweeps.
Figure 2: The signature of an incomplete selective sweep in the region containing the lactase (LCT) gene.
Figure 3: Effects of demography and ascertainment bias on tests of selection.

References

  1. Akey, J. M., Zhang, G., Zhang, K., Jin, L. & Shriver, M. D. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 12, 1805–1814 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Andolfatto, P. Adaptive evolution of non-coding DNA in Drosophila. Nature 437, 1149–1152 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Bustamante, C. D. et al. Natural selection on protein-coding genes in the human genome. Nature 437, 1153–1157 (2005). This paper reports a genome-wide scan for selection in humans based on a derivative of the MacDonald–Kreitman test.

    Article  CAS  PubMed  Google Scholar 

  4. Sabeti, P. C. et al. Positive natural selection in the human lineage. Science 312, 1614–1620 (2006). This review contains a comprehensive list of genes that are thought to be under selection in humans.

    Article  CAS  PubMed  Google Scholar 

  5. Williamson, S. H. et al. Localizing recent adaptive evolution in the human genome. PLoS Genet. 3, e90 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wang, E. T., Kodama, G., Baldi, P. & Moyzis, R. K. Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc. Natl Acad. Sci. USA 103, 135–140 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, New York, 1983).

    Book  Google Scholar 

  8. Gillespie, J. H. The Causes of Molecular Evolution (Oxford Univ. Press, New York, 1991).

    Google Scholar 

  9. Evans, P. D. et al. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309, 1717–1720 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Enard, W. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Bamshad, M. & Wooding, S. P. Signatures of natural selection in the human genome. Nature Rev. Genet. 4, 99A–111A (2003).

    Article  CAS  Google Scholar 

  12. Blanchette, M. & Tompa, M. Discovery of regulatory elements by a computational method for phylogenetic footprinting. Genome Res. 12, 739–748 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Eyre-Walker, A. & Keightley, P. D. High genomic deleterious mutation rates in hominids. Nature 397, 344–347 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Eyre-Walker, A., Keightley, P. D., Smith, N. G. C. & Gaffney, D. Quantifying the slightly deleterious model of molecular evolution. Mol. Biol. Evol. 19, 2142–2149 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Eyre-Walker, A., Woolfit, M. & Phelps, T. The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173, 891–900 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80, 727–739 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Clark, A. G. et al. Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science 302, 1960–1963 (2003). This paper provides a list of genes under positive selection in the human evolutionary lineage based on the ratio of non-synonymous to synonymous mutations.

    Article  CAS  PubMed  Google Scholar 

  19. Consortium, T. C. S. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005).

    Article  CAS  Google Scholar 

  20. Nielsen, R. et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 3, e170 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wyckoff, G. J., Wang, W. & Wu, C. I. Rapid evolution of male reproductive genes in the descent of man. Nature 403, 304–309 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Swanson, W. J., Nielsen, R. & Yang, Q. Pervasive adaptive evolution in mammalian fertilization proteins. Mol. Biol. Evol. 20, 18–20 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Gavrilets, S. Rapid evolution of reproductive barriers driven by sexual conflict. Nature 403, 886–889 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Kaplan, N. L., Hudson, R. R. & Langley, C. H. The hitchhiking effect revisited. Genetics 123, 887–899 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Maynard Smith, J. & Haigh, J. The hitch-hiking effect of a favorable gene. Genet. Res. 23, 23–35 (1974). The original paper describing the effect of a selective sweep in a population.

    Article  Google Scholar 

  26. Braverman, J. M., Hudson, R. R., Kaplan, N. L., Langley, C. H. & Stephan, W. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. Genetics 140, 783–796 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Barton, N. The effect of hitch-hiking on neutral genealogies. Genet. Res. 72, 123–133 (1998).

    Article  CAS  Google Scholar 

  28. Stephan, W., Song, Y. S. & Langley, C. H. The hitchhiking effect on linkage disequilibrium between linked neutral loci. Genetics 172, 2647–2663 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Simoons, F. J. Primary adult lactose intolerance and milking habit — a problem in biologic and cultural interrelations. 2. A culture historical hypothesis. Am. J. Dig. Dis. 15, 695–710 (1970).

    Article  CAS  PubMed  Google Scholar 

  30. Cavalli-Sforza, L. Analytic review: some current problems of population genetics. Am. J. Hum. Genet. 25, 82–104 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Beja-Pereira, A. et al. Gene–culture coevolution between cattle milk protein genes and human lactase genes. Nature Genet. 35, 311–313 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Bersaglieri, T. et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Burger, J., Kirchner, M., Bramanti, B., Haak, W. & Thomas, M. G. Absence of the lactase-persistence-associated allele in early Neolithic Europeans. Proc. Natl Acad. Sci. USA 104, 3736–3741 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bersaglieri, T. et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tishkoff, S. A. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nature Genet. 39, 31–40 (2007). A recent paper that demonstrates positive selection acting independently on different lactase alleles that confer lactose tolerance in adults, in African and European populations.

    Article  CAS  PubMed  Google Scholar 

  36. Tishkoff, S. A. et al. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293, 455–462 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Verrelli, B. C., Argyropoulos, G., Destro-Bisol, G., Williams, S. M. & Tishkoff, S. A. Signature of selection at the G6PD locus inferred from patterns of nucleotide variation and linkage disequilibrium in Africans. Am. J. Hum. Genet. 69, 395–395 (2001).

    Google Scholar 

  38. Saunders, M. A., Hammer, M. F. & Nachman, M. W. Nucleotide variability at G6PD and the signature of malarial selection in humans. Genetics 162, 1849–1861 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Sabeti, P. C. et al. Detecting recent positive selection in the human genome from haplotype structure. Nature 419, 832–837 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. A map of recent positive selection in the human genome. PLoS Biol. 4, e72 (2006). This paper provides the result of a genome-wide scan for selective sweeps based on haplotype structure information.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet. 37, 129–137 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Thompson, E. E. et al. CYP3A variation and the evolution of salt-sensitivity variants. Am. J. Hum. Genet. 75, 1059–1069 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Osier, M. V. et al. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am. J. Hum. Genet. 1, 84–99 (2002).

    Article  Google Scholar 

  44. Gilad, Y., Bustamante, C. D., Lancet, D. & Paabo, S. Natural selection on the olfactory receptor gene family in humans and chimpanzees. Am. J. Hum. Genet. 73, 489–501 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Carlson, C. S. et al. Genomic regions exhibiting positive selection identified from dense genotype data. Genome Res. 15, 1553–1565 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989). This paper describes the most common methods for detecting selection based on population genetic data.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Fay, J. C. & Wu, C. I. Hitchhiking under positive Darwinian selection. Genetics 155, 1405–1413 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Hinds, D. A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Nielsen, R. et al. Genomic scans for selective sweeps using SNP data. Genome Res. 15, 1566–1575 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Henikoff, S. & Malik, H. S. Selfish drivers. Nature 417, 227–227 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. 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. 70, 155–174 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Slatkin, M. & Wiehe, T. Genetic hitch-hiking in a subdivided population. Genet. Res. 71, 155–160 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Lewontin, R. C. & Krakauer, J. Distribution of gene frequency as a test of theory of selective neutrality of polymorphisms. Genetics 74, 175–195 (1973). The original paper discussing the effect of selection on measures of population subdivision.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Weir, B. S., Cardon, L. R., Anderson, A. D., Nielsen, D. M. & Hill, W. G. Measures of human population structure show heterogeneity among genomic regions. Genome Res. 15, 1468–1476 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kayser, M., Brauer, S. & Stoneking, M. A genome scan to detect candidate regions influenced by local natural selection in human populations. Mol. Biol. Evol. 20, 893–900 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

  57. Simonsen, K. L., Churchill, G. A. & Aquadro, C. F. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141, 413–429 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Andolfatto, P. & Przeworski, M. A genome-wide departure from the standard neutral model in natural populations of Drosophila. Genetics 156, 257–268 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Przeworski, M., Hudson, R. R. & Di Rienzo, A. Adjusting the focus on human variation. Trends Genet. 16, 296–302 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Nielsen, R. Statistical tests of selective neutrality in the age of genomics. Heredity 86, 641–647 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Stajich, J. E. & Hahn, M. W. Disentangling the effects of demography and selection in human history. Mol. Biol. Evol. 22, 63–73 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Wall, J. D., Andolfatto, P. & Przeworski, M. Testing models of selection and demography in Drosophila simulans. Genetics 162, 203–216 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Galtier, N., Depaulis, F. & Barton, N. H. Detecting bottlenecks and selective sweeps from DNA sequence polymorphism. Genetics 155, 981–987 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Jensen, J. D., Kim, Y., DuMont, V. B., Aquadro, C. F. & Bustamante, C. D. Distinguishing between selective sweeps and demography using DNA polymorphism data. Genetics 170, 1401–1410 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Edmonds, C. A., Lillie, A. S. & Cavalli-Sforza, L. L. Mutations arising in the wave front of an expanding population. Proc. Natl Acad. Sci. USA 101, 975–979 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Klopfstein, S., Currat, M. & Excoffier, L. The fate of mutations surfing on the wave of a range expansion. Mol. Biol. Evol. 23, 482–490 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Nielsen, R. & Signorovitch, J. Correcting for ascertainment biases when analyzing SNP data: applications to the estimation of linkage disequilibrium. Theor. Popul. Biol. 63, 245–255 (2003).

    Article  PubMed  Google Scholar 

  68. Nielsen, R., Hubisz, M. J. & Clark, A. G. Reconstituting the frequency spectrum of ascertained single-nucleotide polymorphism data. Genetics 168, 2373–2382 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kong, A. et al. A high-resolution recombination map of the human genome. Nature Genet. 10, 10 (2002).

    Google Scholar 

  70. Myers, S., Bottolo, L., Freeman, C., McVean, G. & Donnelly, P. A fine-scale map of recombination rates and hotspots across the human genome. Science 310, 321–324 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Teshima, K. M., Coop, G. & Przeworski, M. How reliable are empirical genomic scans for selective sweeps? Genome Res. 16, 702–712 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Teshima, K. M. & Przeworski, M. Directional positive selection on an allele of arbitrary dominance. Genetics 172, 713–718 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. MacCallum, C. & Hill, E. Being positive about selection. PLoS Biol. 4, 293–295 (2006).

    Article  CAS  Google Scholar 

  74. Shu, W. et al. Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc. Natl Acad. Sci. USA 102, 9643–9648 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Williams, G. C. Adaptation and Natural Selection: A Critique of Some Current Evolutionary Thought (Princeton Univ. Press, Princeton, 1966).

    Google Scholar 

  76. Gould, S. J. & Lewontin, R. C. Spandrels of San-Marco and the Panglossian paradigm — a critique of the adaptationist program. Proc. R. Soc. London Series B Biol. Sci. 205, 581–598 (1979).

    CAS  Google Scholar 

  77. Diaz, G. A. et al. Gaucher disease: The origins of the Ashkenazi Jewish N370S and 84GG acid β-glucosidase mutations. Am. J. Hum. Genet. 66, 1821–1832 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Schwartz, K., Carrier, L., Guicheney, P. & Komajda, M. Molecular-basis of familial cardiomyopathies. Circulation 91, 532–540 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nature Genet. 39, 770–775 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336–1341 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Verrelli, B. C. et al. Evidence for balancing selection from nucleotide sequence analyses of human G6PD. Am. J. Hum. Genet. 71, 1112–1128 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Allen, S. J. et al. α+-thalassemia protects children against disease caused by other infections as well as malaria. Proc. Natl Acad. Sci. USA 94, 14736–14741 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Schroeder, S. A., Gaughan, D. M. & Swift, M. Protection against bronchial-asthma by Cftr δ-f508 mutation — a heterozygote advantage in cystic-fibrosis. Nature Med. 1, 703–705 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. Neel, J. V. Diabetes mellitus: a 'thrifty' genotype rendered detrimental by 'progress'? Am. J. Hum. Genet. 14, 353–362 (1962).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Thomas, P. D. & Kejariwal, A. Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: evolutionary evidence for differences in molecular effects. Proc. Natl Acad. Sci. USA 101, 15398–15403 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zlotogora, J. Multiple mutations responsible for frequent genetic diseases in isolated populations. Eur. J. Hum. Genet. 15, 272–278 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Ng, P. C. & Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 11, 863–874 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sunyaev, S. et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 10, 591–597 (2001). This paper describes the most popular bioinformatical method for predicting disease mutations without phenotypic data.

    Article  CAS  PubMed  Google Scholar 

  91. Sabeti, P. C. et al. Detecting recent positive selection in the human genome from haplotype structure. Nature 419, 832–837 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. Fan, Y., Linardopoulou, E., Friedman, C., Williams, E. & Trask, B. J. Genomic structure and evolution of the ancestral chromosome fusion site in 2q13–12q14.1 and paralogous regions on other human chromosomes. Genome Res. 12, 1651–1662 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kim, Y. & Stephan, W. Detecting a local signature of genetic hitchhiking along a recombining chromosome. Genetics 160, 765–777 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Hudson, R. R., Kreitman, M. & Aguade, M. A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153–159 (1987). The original paper describing the combined use of divergence and diversity data to detect selection.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembrey, M. E. Localisation of a gene implicated in a severe speech and language disorder. Nature Genet. 18, 168–170 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Lai, C. S. et al. The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. Am. J. Hum. Genet. 67, 357–368 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. & Monaco, A. P. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Zhang, J., Webb, D. M. & Podlaha, O. Accelerated protein evolution and origins of human-specific features: Foxp2 as an example. Genetics 162, 1825–1835 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Mekel-Bobrov, N. et al. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309, 1720–1722 (2005).

    Article  CAS  PubMed  Google Scholar 

  100. 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 313, 172 (2006).

    Article  CAS  PubMed  Google Scholar 

  101. Yu, F. L. et al. Comment on 'Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens'. Science 316, 367 (2007).

    Article  CAS  Google Scholar 

  102. Mekel-Bobrov, N. et al. The ongoing adaptive evolution of ASPM and microcephalin is not explained by increased intelligence. Hum. Mol. Genet. 16, 600–608 (2007).

    Article  CAS  PubMed  Google Scholar 

  103. Nielsen, R. Estimation of population parameters and recombination rates from single nucleotide polymorphisms. Genetics 154, 931–942 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Clark, A. G., Hubisz, M. J., Bustamante, C. D., Williamson, S. H. & Nielsen, R. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 15, 1496–1502 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hudson, R. R. Generating samples under a Wright–Fisher neutral model of genetic variation. Bioinformatics 18, 337–338 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank D. Reich, M. Przeworski and two anonymous reviewers for their helpful comments on earlier versions of this manuscript. This work was supported by Danmarks Grundforskningsfond and the US National Insitutes of Health grants R01HG003229 and U01HL084706.

Author information

Authors and Affiliations

  1. Center for Comparative Genomics, University of Copenhagen, Universitetsparken 15, Kbh Ø, 2100, Denmark

    Rasmus Nielsen & Ines Hellmann

  2. Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, 60637, Illinois, USA

    Melissa Hubisz

  3. Department of Biological Statistics and Computational Biology, Cornell University, 1198 Comstock Hall, Ithaca, 14853, New York, USA

    Carlos Bustamante

  4. Department of Molecular Biology and Genetics, Cornell University, 107 Biotechnology Building, Ithaca, 14853, New York, USA

    Andrew G. Clark

Authors
  1. Rasmus Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ines Hellmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa Hubisz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Bustamante
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew G. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rasmus Nielsen.

Related links

Related links

DATABASES

OMIM

Alström syndrome

Crohn disease

cystic fibrosis

familial hypertrophic cardiomyopathy

FURTHER INFORMATION

Rasmus Nielsen's homepage

Haplotter genome browser

International HapMap Project

Seattle SNP database

Glossary

Genetic drift

The stochastic change in population frequency of a mutation due to the sampling process that is inherent in reproduction.

Adaptation

Heritable changes in genotype or phenotype that result in increased fitness.

Fitness

A measure of the capacity of an organism to survive and reproduce.

Effective population size (Ne)

The size of a population measured by the expected effect (through genetic drift) of the population size on genetic variablity. Ne is typically much lower than the actual population size (N).

Selective sweep

The process by which new favourable mutations become fixed so quickly that physically linked alleles also become either fixed or lost depending on the phase of the linkage.

Linkage disequilibrium

A measure of genetic associations between alleles at different loci, which indicates whether allelic or marker associations on the same chromosome are more common than expected.

Fixation

Describes the situation in which a mutation has achieved a frequency of 100% in a natural population.

Site frequency spectrum

The distribution of allele frequencies in a single site of a DNA sequence averaged over multiple sites.

Haplotype

Allelic composition over a contiguous chromosome stretch.

Whole-genome association studies

Also known as genome-wide association studies. Genetic variants across the whole genome (or markers linked to these variants) are genotyped in a population for which phenotypic information is available (such as disease occurrence, or a range of different trait values). If a correlation is observed between genotype and phenotype, there is said to be an association between the variant and the disease or trait.

Meiotic drive

Any process that causes some alleles to be overrepresented in gametes formed during meiosis.

Population bottleneck

A marked reduction in population size followed by the survival and expansion of a small random sample of the original population.

Population structure

A departure from random mating that is typically caused by geographical subdivision.

Balancing selection

A selection regime that results in the maintenance of two or more alleles at a single locus in a population.

Genetic hitch-hiking

The increase if frequency of a selective neutral or weakly selected mutation due to linkage with a positively selected mutation.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nielsen, R., Hellmann, I., Hubisz, M. et al. Recent and ongoing selection in the human genome. Nat Rev Genet 8, 857–868 (2007). https://doi.org/10.1038/nrg2187

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg2187

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing