Nonadaptive Genetic Change in Human and Primate Evolution

Diogo Meyer, Universidade de São Paulo, São Paulo, Brazil
Eugene E Harris, City University of New York, New York, USA

Published online: April 2013

DOI: 10.1002/9780470015902.a0024607

Evolutionary change can occur by nonadaptive processes, such as random genetic drift, and as a consequence of selection on linked genetic variants. In addition, if selective regimes change over time, an allele currently at a high frequency because of past fitness advantage may be suboptimal for its present environment. Small effective population size along the human lineage increased the influence of drift, rendering mutations with slight effects on fitness effectively neutral. Demographic events like spatial expansions and population bottlenecks shape most of the genetic variation within and among modern populations. Natural selection itself may also contribute to nonadaptive or maladaptive change by increasing the frequency of linked deleterious variants. Also, certain maladaptive alleles may have increased in frequency because of compensating fitness advantages they provide.

Key Concepts:

  • Reduced effective population size along the human lineage led to an increase in the influence of genetic drift and a reduction in the efficacy of natural selection, especially for mutations with small selective effects. Evidence for this can be seen in comparisons of measures of natural selection in lineages having different effective population sizes.
  • Genome-wide variation within and between human populations can be almost entirely explained by random drift and demographic forces other natural selection.
  • Spatial expansions in human evolutionary history may cause gene surfing, in which low frequency alleles at the wave of advance can reach high frequencies and spread over large areas merely due to the effects of intense genetic drift. Nonadaptive gene surfing might be a better explanation than adaptive evolution for some high frequency, widespread genetic variants.
  • Population bottlenecks in human evolutionary history can lead to increases in drift and reductions in the efficacy of purifying selection. This leads to an increase in the fraction of slightly deleterious mutations present in human populations that have experienced recent bottlenecks.
  • Natural selection on alleles can result in nonadaptive shifts in the frequencies of alleles that are closely linked to them. Such linkage effects can lead to the increased frequencies of mildly deleterious alleles if they are linked to a beneficial variant, and can interfere with the effectiveness of adaptive evolution in promoting an advantageous allele if it is linked to a deleterious allele.
  • Caution should be exercised in interpreting patterns of genetic variation in human populations as being adaptive without thoroughly ruling out nonadaptive explanations.

Keywords: population genetics; evolution; natural selection; positive selection; purifying selection; human evolution; gene surfing; adaptation; linkage; effective population size; genetic drift; nonadaptive

Figure 1. The probability of fixation of a new variant with respect to the neutral expectation of 1/(2N) graphed as a function of the product of the effective population size and the selection coefficient of the variant (Ne×s). The dashed lines represent cases in which s = –10–5 but Ne takes on different values, either 10 000 (upper dashed line) or 100 000 (lower dashed line).
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 References
    Andolfatto P (2007) Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome. Genome Research 17(12): 1755–1762.
    Barton NH (1995) Linkage and the limits to natural selection. Genetics 140(2): 821–841.
    Bersaglieri T, Sabeti PC, Patterson N et al. (2004) Genetic signatures of strong recent positive selection at the lactase gene. American Journal of Human Genetics 74(6): 1111–1120.
    Boyko AR, Williamson SH, Indap AR et al. (2008) Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genetics 4(5): e1000083.
    Burgess R and Yang Z (2008) Estimation of hominoid ancestral population sizes under Bayesian coalescent models incorporating mutation rate variation and sequencing errors. Molecular Biology and Evolution 25(9): 1979–1994.
    Bustamante CD, Fledel-Alon A, Williamson S et al. (2005) Natural selection on protein-coding genes in the human genome. Nature 437: 1153–1157.
    Cai JJ, Macpherson JM, Sella G and Petrov DA (2009) Pervasive hitchhiking at coding and regulatory sites in humans. PLoS Genetics 5: e1000336.
    Carter AJR and Nguyen AQ (2011) Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles. BMC Medical Genetics 12: 160.
    book Cavalli-Sforza LL and Bodmer WF (1971) The Genetics of Human Populations. San Francisco: W. H. Freeman. (reprinted 1999 by Dover Publications).
    Charlesworth B, Morgan MT and Charlesworth D (1993) The effect of deleterious mutations on neutral molecular variation. Genetics 134(4): 1289–1303.
    Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437(7055): 69–87.
    Chun S and Fay JC (2009) Identification of deleterious mutations within three human genomes. Genome Research 19(9): 1553–1561.
    Chun S and Fay JC (2011) Evidence for hitchhiking of deleterious mutations within the human genome. PLoS Genetics 7(8): e1002240.
    Coop G, Pickrell JK, Novembre J et al. (2009) The role of geography in human adaptation. PLoS Genetics 5(6): e1000500.
    Di Rienzo A and Hudson RR (2005) An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends in Genetics 21(11): 596–601.
    Eyre-Walker A (2006) The genomic rate of adaptive evolution. Trends in Ecology and Evolution 21: 569–575.
    Eyre-Walker A and Keightley PD (2009) Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Molecular Biology and Evolution 26: 2097–2108.
    Fay JC, Wyckoff GJ and Wu CI (2001) Positive and negative selection on the human genome. Genetics 158: 1227–1234.
    Fumagalli M, Sironi M, Pozzoli U et al. (2011) Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genetics 7(11): e1002355.
    Gillespie JH (2001) Is the population size of a species relevant to its evolution? Evolution 55(11): 2161–2169.
    Gleibermann L (1973) Blood pressure and dietary salt in human populations. Ecology Food and Nutrition 2: 143–156.
    Gojobori J, Tang H, Akey JM and Wu CI (2007) Adaptive evolution in humans revealed by the negative correlation between the polymorphism and fixation phases of evolution. Proceedings of the National Academy of Sciences of the USA 104(10): 3907–3912.
    Halligan DL, Oliver F, Eyre-Walker A et al. (2010) Evidence for pervasive adaptive protein evolution in wild mice. PLoS Genetics 6(1): 1–9.
    Jensen JD and Bachtrog D (2011) Characterizing the influence of effective population size on the rate of adaptation: Gillespie's Darwin domain. Genome Biology and Evolution 3: 687–701.
    Klopfstein S, Currat M and Excoffier L (2006) The fate of mutations surfing on the wave of a range expansion. Molecular Biology and Evolution 23(3): 482–490.
    Kosiol C, Vinar T, da Fonseca RR et al. (2008) Patterns of positive selection in six mammalian genomes. PLoS Genetics 4(8): e1000144.
    Li H and Durbin R (2011) Inference of human population history from individual whole-genome sequences. Nature 475(7357): 493–496.
    Li Y, Vinckenbosch N, Tian G et al. (2010) Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Nature Genetics 42: 969–972.
    Lohmueller KE, Albrechtsen A, Li Y et al. (2011) Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genetics 7(10): e1002326.
    Lohmueller KE, Indap AR, Schmidt S et al. (2008) Proportionally more deleterious genetic variation in European than in African populations. Nature 451: 994–997.
    Manolio TA, Collins FS, Cox NJ et al. (2009) Finding the missing heritability of complex diseases. Nature 461(7265): 747–753.
    McEvoy B, Beleza S and Shriver MD (2006) The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model. Human Molecular Genetics 15(Spec no. 2): R176–R181.
    McVicker G, Gordon D, Davis C and Green P (2009) Widespread genomic signatures of natural selection in hominid evolution. PLoS Genetics 5: e1000471.
    Neel JV (1962) Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? American Journal of Human Genetics 14: 353–362.
    Nielsen R, Hubisz MJ, Hellmann I et al. (2009) Darwinian and demographic forces affecting human protein coding genes. Genome Research 19: 838–849.
    Novembre J, Johnson T, Bryc K et al. (2008) Genes mirror geography within Europe. Nature 456: 98–101.
    Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246: 96–98.
    Phifer-Rixey M, Bonhomme F, Boursot P et al. (2012) Adaptive evolution and effective population size in wild house mice. Molecular Biology and Evolution 29(10): 2949–2955.
    Pier GB, Grout M, Zaidi T et al. (1998) Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 393(6680): 79–82.
    Prugnolle F, Manica A and Balloux F (2005) Geography predicts neutral genetic diversity of human populations. Current Biology 15: R159–R160.
    Reed FA and Aquadro CF (2006) Mutation, selection and the future of human evolution. Trends in Genetics 22(9): 479–484.
    Sawyer SA, Parsch J, Zhang Z and Hartl DL (2007) Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila. Proceedings of the National Academy of Sciences of the USA 104: 6504–6510.
    Smith JM and Haigh J (1974) The hitch-hiking effect of a favourable gene. Genetics Research 23(1): 23–35.
    Strachan DP (1989) Hay fever, hygiene, and household size. British Medical Journal 299(6710): 1259–1260.
    Thompson EE, Kuttab-Boulos H, Witonsky D et al. (2004) CYP3A variation and the evolution of salt-sensitivity variants. American Journal of Human Genetics 75(6): 1059–1069.
    Travis JM, Munkemuller T, Burton OJ et al. (2007) Deleterious mutations can surf to high densities on the wave front of an expanding population. Molecular Biology and Evolution 24: 2334–2343.
    Welch JJ (2006) Estimating the genome wide rate of adaptive protein evolution in Drosophila. Genetics 173: 821–837.
 Further Reading
    book Cavalli-Sforza LL, Menozzi P and Piazza A (1994) The History and Geography of Human Genes. Princeton: Princeton University Press.
    Edmonds CA, Lillie AS and Cavalli-Sforza LL (2004) Mutations arising in the wave front of an expanding population. Proceedings of the National Academy of Sciences of the USA 101: 975–979.
    Ellegren H (2008) Comparative genomics and the study of evolution by natural selection. Molecular Ecology 17(21): 4586–4596.
    Excoffier L and Ray N (2008) Surfing during population expansions promotes genetic revolutions and structuration. Trends in Ecology and Evolution 23: 347–351.
    Harris EE (2010) Nonadaptive processes in human and primate evolution. American Journal of Physical Anthropology 143(Suppl. 51): 13–45.
    Hofer T, Ray N, Wegmann D and Excoffier L (2009) 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 73: 95–108.
    book Lynch M (2007) The Origins of Genome Architecture. Sunderland, Massachusetts: Sinauer Associates, Inc.
    Nielsen R (2009) Adaptionism-30 years after Gould and Lewontin. Evolution 63: 2487–2490.
    Slatkin M (2008) Linkage disequilibrium – understanding the evolutionary past and mapping the medical future. Nature Reviews Genetics 9: 477–485.
    Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398–411.

Related Sub-Topics:

Evolution: Theories and Ideas | Selection and Variation | Human Evolution | Population Structure and Genetics
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Article Title: Nonadaptive Genetic Change in Human and Primate Evolution
 
How to Cite close
Meyer, Diogo, and Harris, Eugene E(Apr 2013) Nonadaptive Genetic Change in Human and Primate Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024607]