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.

Genomic signatures of selection at linked sites: unifying the disparity among species

Key Points

  • Population genetics theory supplies powerful predictions about how natural selection, interacting with genetic linkage, will sculpt the genomic landscape of nucleotide polymorphism.

  • Genetic hitch-hiking of neutral alleles linked to a beneficial mutation undergoing a 'hard' selective sweep, or the selective removal by background selection of deleterious mutations, will more greatly affect patterns of polymorphism in genomic regions with little recombination.

  • Despite supporting evidence for genetic hitch-hiking and background selection from many organisms, empiricists have documented extreme disparities among species.

  • The dominant features that could drive variation in linked selection among species include the potential roles for selective sweeps being 'hard' or 'soft' and the concealing effects of demography and confounding genomic variables.

  • We advocate targeted studies of closely related species that differ in key variables to help clarify the causes of among-species disparities and to unify our understanding of how selection and linkage interact to shape genome evolution.

Abstract

Population genetics theory supplies powerful predictions about how natural selection interacts with genetic linkage to sculpt the genomic landscape of nucleotide polymorphism. Both the spread of beneficial mutations and the removal of deleterious mutations act to depress polymorphism levels, especially in low-recombination regions. However, empiricists have documented extreme disparities among species. Here we characterize the dominant features that could drive differences in linked selection among species — including roles for selective sweeps being 'hard' or 'soft' — and the concealing effects of demography and confounding genomic variables. We advocate targeted studies of closely related species to unify our understanding of how selection and linkage interact to shape genome evolution.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: A hypothetical chromosome exhibiting a 'selection at linked sites' pattern.
Figure 2: Modes of selection on linked genetic variation and factors affecting them.
Figure 3: Taxonomic support for different signatures of selection at linked sites.

References

  1. 1

    Wiehe, T. H. E. & Stephan, W. Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster. Mol. Biol. Evol. 10, 842–854 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Hudson, R. R. & Kaplan, N. L. Deleterious background selection with recombination. Genetics 141, 1605–1617 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Maynard Smith, J. & Haigh, J. Hitch-hiking effect of a favorable gene. Genet. Res. 23, 23–35 (1974). This is the classic theoretical study that describes the process of genetic hitch-hiking.

    Article  Google Scholar 

  4. 4

    Hill, W. G. & Robertson, A. Effect of linkage on limits to artificial selection. Genet. Res. 8, 269–294 (1966). Here, the classic model is presented of how linked selected loci interfere with each other's ability to fix the favoured alleles in the population.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Felsenstein, J. The evolutionary advantage to recombination. Genetics 78, 737–756 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Begun, D. J. & Aquadro, C. F. Levels of naturally-occurring DNA polymorphism correlate with recombination rates in Drosophila melanogaster. Nature 356, 519–520 (1992). This seminal study demonstrates that selection at linked sites yields a general pattern on genetic diversity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Aguade, M., Miyashita, N. & Langley, C. H. Reduced variation in the yellow-achaete-scute region in natural populations of Drosophila melanogaster. Genetics 122, 607–615 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Stephan, W. & Langley, C. H. Molecular genetic-variation in the centromeric region of the X-chromosome in 3 Drosophila ananassae populations. 1. Contrasts between the vermilion and forked loci. Genetics 121, 89–99 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Smukowski, C. S. & Noor, M. A. Recombination rate variation in closely related species. Heredity 107, 496–508 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Massouras, A. et al. Genomic variation and its impact on gene expression in Drosophila melanogaster. PLoS Genet. 8, e1003055 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Leffler, E. M. et al. Revisiting an old riddle: what determines genetic diversity levels within species? PLoS Biol. 10, e1001388 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Barton, N. H. Genetic hitchhiking. Phil. Trans. R. Soc. B 355, 1553–1562 (2000).

    Article  CAS  Google Scholar 

  13. 13

    Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Frankham, R. How closely does genetic diversity in finite populations conform to predictions of neutral theory? Large deficits in regions of low recombination. Heredity 108, 167–178 (2012).

    Article  CAS  Google Scholar 

  15. 15

    Kaplan, N. L., Hudson, R. R. & Langley, C. H. The “hitchhiking effect” revisited. Genetics 123, 887–899 (1989). The important theoretical extension of genetic hitch-hiking is described here — from a single episode of selection to recurrent selective sweeps — in a genome that has variable recombination rates across different genomic regions.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Charlesworth, B., Betancourt, A. J., Kaiser, V. B. & Gordo, I. Genetic recombination and molecular evolution. Cold Spring Harb. Symp. Quant. Biol. 74, 177–186 (2009).

    Article  CAS  Google Scholar 

  17. 17

    Comeron, J. M., Williford, A. & Kliman, R. M. The Hill–Robertson effect: evolutionary consequences of weak selection and linkage in finite populations. Heredity 100, 19–31 (2008).

    Article  CAS  Google Scholar 

  18. 18

    Barton, N. H. Genetic linkage and natural selection. Phil. Trans. R. Soc. 365, 2559–2569 (2010).

    Article  CAS  Google Scholar 

  19. 19

    Walczak, A. M., Nicolaisen, L. E., Plotkin, J. B. & Desai, M. M. The structure of genealogies in the presence of purifying selection: a fitness-class coalescent. Genetics 190, 753–779 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Charlesworth, B., Morgan, M. T. & Charlesworth, D. The effect of deleterious mutations on neutral molecular variation. Genetics 134, 1289–1303 (1993). This classic paper introduces the notion that background selection reduces neutral genetic variation disproportionately in low-recombination regions, similarly to the effects of recurrent selective sweeps.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Charlesworth, B. The effects of deleterious mutations on evolution at linked sites. Genetics 190, 5–22 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Eyre-Walker, A. & Keightley, P. D. The distribution of fitness effects of new mutations. Nature Rev. Genet. 8, 610–618 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Lohmueller, K. E. et al. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genet. 7, e1002326 (2011). This exemplary recent empirical study incorporates background selection as a part of the null model of molecular evolution shaping genome-wide patterns of genetic variation in humans.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    McVicker, G., Gordon, D., Davis, C. & Green, P. Widespread genomic signatures of natural selection in Hominid evolution. PLoS Genet. 5, e1000471 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    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 

  26. 26

    Sella, G., Petrov, D. A., Przeworski, M. & Andolfatto, P. Pervasive natural selection in the Drosophila genome? PLoS Genet. 5, e1000495 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Charlesworth, D., Charlesworth, B. & Morgan, M. T. The pattern of neutral molecular variation under the background selection model. Genetics 141, 1619–1632 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Kaiser, V. B. & Charlesworth, B. The effects of deleterious mutations on evolution in non-recombining genomes. Trends Genet. 25, 9–12 (2009).

    Article  CAS  Google Scholar 

  29. 29

    Andolfatto, P. Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome. Genome Res. 17, 1755–1762 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Macpherson, J. M., Sella, G., Davis, J. C. & Petrov, D. A. Genomewide spatial correspondence between nonsynonymous divergence and neutral polymorphism reveals extensive adaptation in Drosophila. Genetics 177, 2083–2099 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Payseur, B. A. & Nachman, M. W. Gene density and human nucleotide polymorphism. Mol. Biol. Evol. 19, 336–340 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Kim, S. et al. Recombination and linkage disequilibrium in Arabidopsis thaliana. Nature Genet. 39, 1151–1155 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Hernandez, R. D. et al. Classic selective sweeps were rare in recent human evolution. Science 331, 920–924 (2011). This empirical study emphasizes the possibility that hard sweeps might not best explain much adaptation in recent human evolution, suggesting that soft sweeps and polygenic selection are important alternatives.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Sattath, S., Elyashiv, E., Kolodny, O., Rinott, Y. & Sella, G. Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans. PLoS Genet. 7, e1001302 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Flowers, J. M. et al. Natural selection in gene-dense regions shapes the genomic pattern of polymorphism in wild and domesticated rice. Mol. Biol. Evol. 29, 675–687 (2012). Here, the authors describe an important empirical demonstration of the confounding influence of genomic variables in detecting selection at linked sites.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Barton, N. H. Linkage and the limits to natural selection. Genetics 140, 821–841 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Betancourt, A. J. & Presgraves, D. C. Linkage limits the power of natural selection in Drosophila. Proc. Natl Acad. Sci. USA 99, 13616–13620 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Presgraves, D. C. Recombination enhances protein adaptation in Drosophila melanogaster. Curr. Biol. 15, 1651–1656 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Mackay, T. F. et al. The Drosophila melanogaster genetic reference panel. Nature 482, 173–178 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    McDonald, J. H. & Kreitman, M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Eyre-Walker, A. & Keightley, P. D. Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Mol. Biol. Evol. 26, 2097–2108 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Andolfatto, P., Wong, K. M. & Bachtrog, D. Effective population size and the efficacy of selection on the X chromosomes of two closely related Drosophila species. Genome Biol. Evol. 3, 114–128 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Fay, J. C. Weighing the evidence for adaptation at the molecular level. Trends Genet. 27, 343–349 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Gossmann, T. I., Keightley, P. D. & Eyre-Walker, A. The effect of variation in the effective population size on the rate of adaptive molecular evolution in eukaryotes. Genome Biol. Evol. 4, 658–667 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46

    Ellegren, H. Comparative genomics and the study of evolution by natural selection. Mol. Ecol. 17, 4586–4596 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47

    Begun, D. J. et al. Population genomics: whole-genome analysis of polymorphism and divergence in Drosophila simulans. PLoS Biol. 5, e310 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Hahn, M. W. Toward a selection theory of molecular evolution. Evolution 62, 255–265 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Langley, C. H. et al. Genomic variation in natural populations of Drosophila melanogaster. Genetics 192, 533–598 (2012). This is a thorough population genomic analysis relating polymorphism characteristics to recombination profiles.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Shapiro, J. A. et al. Adaptive genic evolution in the Drosophila genomes. Proc. Natl Acad. Sci. USA 104, 2271–2276 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Charlesworth, B. The role of background selection in shaping patterns of molecular evolution and variation: evidence from variability on the Drosophila X chromosome. Genetics 191, 233–246 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Wright, S. I. & Andolfatto, P. The impact of natural selection on the genome: emerging patterns in Drosophila and Arabidopsis. Annu. Rev. Ecol. Evol. Syst. 39, 193–213 (2008).

    Article  Google Scholar 

  53. 53

    Baudry, E., Kerdelhue, C., Innan, H. & Stephan, W. Species and recombination effects on DNA variability in the tomato genus. Genetics 158, 1725–1735 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Wright, S. I. et al. Testing for effects of recombination rate on nucleotide diversity in natural populations of Arabidopsis lyrata. Genetics 174, 1421–1430 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Nordborg, M. et al. The pattern of polymorphism in Arabidopsis thaliana. PLoS Biol. 3, e196 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Cutter, A. D. & Moses, A. M. Polymorphism, divergence, and the role of recombination in Saccharomyces cerevisiae genome evolution. Mol. Biol. Evol. 28, 1745–1754 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Tenaillon, M. I. et al. Patterns of diversity and recombination along chromosome 1 of maize (Zea mays ssp. mays L.). Genetics 162, 1401–1413 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Cao, J. et al. Whole-genome sequencing of multiple Arabidopsis thaliana populations. Nature Genet. 43, 956–963 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Cutter, A. D. & Choi, J. Y. Natural selection shapes nucleotide polymorphism across the genome of the nematode Caenorhabditis briggsae. Genome Res. 20, 1103–1111 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Rockman, M. V., Skrovanek, S. S. & Kruglyak, L. Selection at linked sites shapes heritable phenotypic variation in C. elegans. Science 330, 372–376 (2010). This is an intriguing demonstration of how selection at linked sites can affect phenotypic (gene expression) variation in addition to neutral nucleotide variation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Hobolth, A., Dutheil, J. Y., Hawks, J., Schierup, M. H. & Mailund, T. Incomplete lineage sorting patterns among human, chimpanzee, and orangutan suggest recent orangutan speciation and widespread selection. Genome Res. 21, 349–356 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Cutter, A. D. & Payseur, B. A. Selection at linked sites in the partial selfer Caenorhabditis elegans. Mol. Biol. Evol. 20, 665–673 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Andersen, E. C. et al. Chromosome-scale selective sweeps shape Caenorhabditis elegans genomic diversity. Nature Genet. 44, 285–290 (2012). This empirical study demonstrates how selective sweeps can eliminate large swathes of genetic variability in self-fertilizing species in addition to the effects of background selection.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Baer, C. F., Miyamoto, M. M. & Denver, D. R. Mutation rate variation in multicellular eukaryotes: causes and consequences. Nature Rev. Genet. 8, 619–631 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Denver, D. R. et al. Variation in base-substitution mutation in experimental and natural lineages of Caenorhabditis nematodes. Genome Biol. Evol. 4, 513–522 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Haag-Liautard, C. et al. Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 445, 82–85 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Lynch, M. et al. A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc. Natl Acad. Sci. USA 105, 9272–9277 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  68. 68

    Ossowski, S. et al. The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana. Science 327, 92–94 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Kong, A. et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488, 471–475 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Schneider, A., Charlesworth, B., Eyre-Walker, A. & Keightley, P. D. A method for inferring the rate of occurrence and fitness effects of advantageous mutations. Genetics 189, 1427–1437 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Gossmann, T. I. et al. Genome wide analyses reveal little evidence for adaptive evolution in many plant species. Mol. Biol. Evol. 27, 1822–1832 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Gillespie, J. H. Is the population size of a species relevant to its evolution? Evolution 55, 2161–2169 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Coop, G. et al. The role of geography in human adaptation. PLoS Genet. 5, e1000500 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Granka, J. M. et al. Limited evidence for classic selective sweeps in African populations. Genetics 192, 1049–1064 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  75. 75

    Pritchard, J. K., Pickrell, J. K. & Coop, G. The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr. Biol. 20, R208–R215 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Karasov, T., Messer, P. W. & Petrov, D. A. Evidence that adaptation in Drosophila is not limited by mutation at single sites. PLoS Genet. 6, e1000924 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Miller, C. R., Joyce, P. & Wichman, H. A. Mutational effects and population dynamics during viral adaptation challenge current models. Genetics 187, 185–202 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78

    Lang, G. I., Botstein, D. & Desai, M. M. Genetic variation and the fate of beneficial mutations in asexual populations. Genetics 188, 647–661 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Hermisson, J. & Pennings, P. S. Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169, 2335–2352 (2005). This important theoretical study models selection from standing genetic variation, to produce soft sweeps.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Storz, J. F. & Wheat, C. W. Integrating evolutionary and functional approaches to infer adaptation at specific loci. Evolution 64, 2489–2509 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Rouzine, I. M. & Coffin, J. M. Multi-site adaptation in the presence of infrequent recombination. Theor. Popul. Biol. 77, 189–204 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    Przeworski, M., Coop, G. & Wall, J. D. The signature of positive selection on standing genetic variation. Evolution 59, 2312–2323 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  83. 83

    Innan, H. & Kim, Y. Pattern of polymorphism after strong artificial selection in a domestication event. Proc. Natl Acad. Sci. USA 101, 10667–10672 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Ohta, T. & Kimura, M. Effect of selected linked locus on heterozygosity of neutral alleles (hitch-hiking effect). Genet. Res. 25, 313–326 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Coop, G. & Ralph, P. Patterns of neutral diversity under general models of selective sweeps. Genetics 192, 205–224 (2012). This recent theoretical extension of recurrent positive selection to partial sweeps helps to generalize the expectations for patterns of genetic variation in genomes.

    Article  PubMed  PubMed Central  Google Scholar 

  86. 86

    Kim, Y. & Maruki, T. Hitchhiking effect of a beneficial mutation spreading in a subdivided population. Genetics 189, 213–226 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Bierne, N. The distinctive footprints of local hitchhiking in a varied environment and global hitchhiking in a subdivided population. Evolution 64, 3254–3272 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Ralph, P. & Coop, G. Parallel adaptation: one or many waves of advance of an advantageous allele? Genetics 186, 647–668 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  89. 89

    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 

  90. 90

    Turchin, M. C. et al. Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nature Genet. 44, 1015–1019 (2012).

    Article  CAS  Google Scholar 

  91. 91

    Pritchard, J. K. & Di Rienzo, A. Adaptation — not by sweeps alone. Nature Rev. Genet. 11, 665–667 (2010).

    Article  CAS  Google Scholar 

  92. 92

    Pavlidis, P., Metzler, D. & Stephan, W. Selective sweeps in multilocus models of quantitative traits. Genetics 192, 225–239 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  93. 93

    Chevin, L. M. & Hospital, F. Selective sweep at a quantitative trait locus in the presence of background genetic variation. Genetics 180, 1645–1660 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  94. 94

    Chun, S. & Fay, J. C. Evidence for hitchhiking of deleterious mutations within the human genome. PLoS Genet. 7, e1002240 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Hartfield, M. & Otto, S. P. Recombination and hitchhiking of deleterious alleles. Evolution 65, 2421–2434 (2011).

    Article  Google Scholar 

  96. 96

    Hadany, L. & Feldman, M. W. Evolutionary traction: the cost of adaptation and the evolution of sex. J. Evol. Biol. 18, 309–314 (2005).

    Article  CAS  Google Scholar 

  97. 97

    Boyko, A. R. et al. Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet. 4, e1000083 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

    Zeng, K. & Charlesworth, B. The joint effects of background selection and genetic recombination on local gene genealogies. Genetics 189, 251–266 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  99. 99

    Gerstein, A. C. & Otto, S. P. Ploidy and the causes of genomic evolution. J. Hered. 100, 571–581 (2009).

    Article  CAS  Google Scholar 

  100. 100

    Stephan, W. Genetic hitchhiking versus background selection: the controversy and its implications. Phil. Trans. R. Soc. 365, 1245–1253 (2010).

    Article  Google Scholar 

  101. 101

    Hudson, R. R. How can the low levels of DNA sequence variation in regions of the Drosophila genome with low recombination rates be explained? Proc. Natl Acad. Sci. USA 91, 6815–6818 (1994).

    Article  CAS  Google Scholar 

  102. 102

    Fiston-Lavier, A. S., Singh, N. D., Lipatov, M. & Petrov, D. A. Drosophila melanogaster recombination rate calculator. Gene 463, 18–20 (2010).

    Article  CAS  Google Scholar 

  103. 103

    True, J. R., Mercer, J. M. & Laurie, C. C. Differences in crossover frequency and distribution among three sibling species of Drosophila. Genetics 142, 507–523 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104

    Hillier, L. W. et al. Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny. PLoS Biol. 5, e167 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

    Mancera, E., Bourgon, R., Brozzi, A., Huber, W. & Steinmetz, L. M. High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454, 479–485 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. 106

    McGaugh, S. E. et al. Recombination modulates how selection affects linked sites in Drosophila. PLoS Biol. 10, e1001422 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. 107

    Kong, A. et al. Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467, 1099–1103 (2010).

    Article  CAS  Google Scholar 

  108. 108

    Dumont, B. L., White, M. A., Steffy, B., Wiltshire, T. & Payseur, B. A. Extensive recombination rate variation in the house mouse species complex inferred from genetic linkage maps. Genome Res. 21, 114–125 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. 109

    Auton, A. et al. A fine-scale chimpanzee genetic map from population sequencing. Science 336, 193–198 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. 110

    Coop, G., Wen, X., Ober, C., Pritchard, J. K. & Przeworski, M. High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 319, 1395–1398 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Sandor, C. et al. Genetic variants in REC8, RNF212, and PRDM9 influence male recombination in cattle. PLoS Genet. 8, e1002854 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. 112

    Ross, J. A. et al. Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination. PLoS Genet. 7, e1002174 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. 113

    Comeron, J. M., Ratnappan, R. & Bailin, S. The many landscapes of recombination in Drosophila melanogaster. PLoS Genet. 8, e1002905 (2012). This is an important experimental demonstration of how different genetic backgrounds yield different profiles of recombination along their genomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Neher, R. A. & Shraiman, B. I. Genetic draft and quasi-neutrality in large facultatively sexual populations. Genetics 188, 975–996 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Charlesworth, D. & Wright, S. I. Breeding systems and genome evolution. Curr. Opin. Genet. Dev. 11, 685–690 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. 116

    Innan, H. & Stephan, W. Distinguishing the hitchhiking and background selection models. Genetics 165, 2307–2312 (2003).

    PubMed  PubMed Central  Google Scholar 

  117. 117

    Charlesworth, B. Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation. Nature Rev. Genet. 10, 195–205 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. 118

    Siol, M., Wright, S. I. & Barrett, S. C. H. The population genomics of plant adaptation. New Phytol. 188, 313–332 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Wakeley, J. Nonequilibrium migration in human history. Genetics 153, 1863–1871 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Stadler, T., Haubold, B., Merino, C., Stephan, W. & Pfaffelhuber, P. The impact of sampling schemes on the site frequency spectrum in nonequilibrium subdivided populations. Genetics 182, 205–216 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. 121

    Cutter, A. D., Wang, G.-X., Ai, H. & Peng, Y. Influence of finite-sites mutation, population subdivision and sampling schemes on patterns of nucleotide polymorphism for species with molecular hyperdiversity. Mol. Ecol. 21, 1345–1359 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. 122

    Chen, Y., Marsh, B. J. & Stephan, W. Joint effects of natural selection and recombination on gene flow between Drosophila ananassae populations. Genetics 155, 1185–1194 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    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  PubMed Central  Google Scholar 

  124. 124

    Eldon, B. & Wakeley, J. Coalescent processes when the distribution of offspring number among individuals is highly skewed. Genetics 172, 2621–2633 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. 125

    Harvey, P. H. & Pagel, M. D. The Comparative Method in Evolutionary Biology (Oxford Univ. Press, 1991).

  126. 126

    O'Brien, S. J. et al. The promise of comparative genomics in mammals. Science 286, 458–481 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. 127

    Steppan, S. J., Phillips, P. C. & Houle, D. Comparative quantitative genetics: evolution of the G matrix. Trends Ecol. Evol. 17, 320–327 (2002).

    Article  Google Scholar 

  128. 128

    Kimura, M. & Crow, J. F. The number of alleles that can be maintained in a finite population. Genetics 49, 725–738 (1964).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129

    Strathern, J. N., Shafer, B. K. & McGill, C. B. DNA-synthesis errors associated with double- strand-break repair. Genetics 140, 965–972 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130

    Holbeck, S. L. & Strathern, J. N. A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147, 1017–1024 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    Kimura, M. Evolutionary rate at molecular level. Nature 217, 624–626 (1968).

    Article  CAS  Google Scholar 

  132. 132

    Stevison, L. & Noor, M. Genetic and evolutionary correlates of fine-scale recombination rate variation in Drosophila persimilis. J. Mol. Evol. 71, 332–345 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. 133

    Hellmann, I., Ebersberger, I., Ptak, S. E., Paabo, S. & Przeworski, M. A neutral explanation for the correlation of diversity with recombination rates in humans. Am. J. Hum. Genet. 72, 1527–1535 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134

    Lercher, M. J. & Hurst, L. D. Human SNP variability and mutation rate are higher in regions of high recombination. Trends Genet. 18, 337–340 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. 135

    Kulathinal, R. J., Stevison, L. S. & Noor, M. A. F. The genomics of speciation in Drosophila: diversity, divergence, and introgression estimated using low-coverage genome sequencing. PLoS Genet. 5, e1000550 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. 136

    Huang, S. W., Friedman, R., Yu, N., Yu, A. & Li, W. H. How strong is the mutagenicity of recombination in mammals? Mol. Biol. Evol. 22, 426–431 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. 137

    Pal, C., Papp, B. & Hurst, L. D. Does the recombination rate affect the efficiency of purifying selection? The yeast genome provides a partial answer. Mol. Biol. Evol. 18, 2323–2326 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. 138

    McVean, G. A. T. & Charlesworth, B. A population genetic model for the evolution of synonymous codon usage: patterns and predictions. Genet. Res. 74, 145–158 (1999).

    Article  Google Scholar 

  139. 139

    Duret, L. Evolution of synonymous codon usage in metazoans. Curr. Opin. Genet. Dev. 12, 640–649 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. 140

    Hershberg, R. & Petrov, D. A. Selection on codon bias. Annu. Rev. Genet. 42, 287–299 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. 141

    Kliman, R. M. & Hey, J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol. Biol. Evol. 10, 1239–1258 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142

    Marais, G., Mouchiroud, D. & Duret, L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc. Natl Acad. Sci. USA 98, 5688–5692 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. 143

    Comeron, J. M. & Kreitman, M. Population, evolutionary and genomic consequences of interference selection. Genetics 161, 389–410 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    Loewe, L. & Charlesworth, B. Background selection in single genes may explain patterns of codon bias. Genetics 175, 1381–1393 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. 145

    Strasburg, J. L. et al. Effective population size is positively correlated with levels of adaptive divergence among annual sunflowers. Mol. Biol. Evol. 28, 1569–1580 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. 146

    Lartillot, N. & Poujol, R. A phylogenetic model for investigating correlated evolution of substitution rates and continuous phenotypic characters. Mol. Biol. Evol. 28, 729–744 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. 147

    Nachman, M. W., Bauer, V. L., Crowell, S. L. & Aquadro, C. F. DNA variability and recombination rates at X-linked loci in humans. Genetics 150, 1133–1141 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. 148

    Bullaughey, K., Przeworski, M. & Coop, G. No effect of recombination on the efficacy of natural selection in primates. Genome Res. 18, 544–554 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. 149

    Nachman, M. W. Patterns of DNA variability at X-linked loci in Mus domesticus. Genetics 147, 1303–1316 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150

    Takahashi, A., Liu, Y. H. & Saitou, N. Genetic variation versus recombination rate in a structured population of mice. Mol. Biol. Evol. 21, 404–409 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. 151

    Geraldes, A., Basset, P., Smith, K. L. & Nachman, M. W. Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination. Mol. Ecol. 20, 4722–4736 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. 152

    Rao, Y., Sun, L., Nie, Q. & Zhang, X. The influence of recombination on SNP diversity in chickens. Hereditas 148, 63–69 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  153. 153

    Fang, L. et al. Positive correlation between recombination rate and nucleotide diversity is shown under domestication selection in the chicken genome. Chinese Sci. Bull. 53, 746–750 (2008).

    Article  CAS  Google Scholar 

  154. 154

    Stump, A. D. et al. Centromere-proximal differentiation and speciation in Anopheles gambiae. Proc. Natl Acad. Sci. USA 102, 15930–15935 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. 155

    Andolfatto, P. & Przeworski, M. Regions of lower crossing over harbor more rare variants in African populations of Drosophila melanogaster. Genetics 158, 657–665 (2001). This empirical study demonstrates how population genetic features other than simply the amount of diversity are affected by selection at linked sites.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. 156

    Hey, J. & Kliman, R. M. Interactions between natural selection, recombination and gene density in the genes of Drosophila. Genetics 160, 595–608 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Charlesworth, B. Background selection and patterns of genetic diversity in Drosophila melanogaster. Genet. Res. 68, 131–149 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. 158

    Kulathinal, R. J., Bennett, S. M., Fitzpatrick, C. L. & Noor, M. A. Fine-scale mapping of recombination rate in Drosophila refines its correlation to diversity and divergence. Proc. Natl Acad. Sci. USA 105, 10051–10056 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  159. 159

    Marais, G. & Piganeau, G. Hill–Robertson interference is a minor determinant of variations in codon bias across Drosophila melanogaster and Caenorhabditis elegans genomes. Mol. Biol. Evol. 19, 1399–1406 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. 160

    Denver, D. R. et al. A genome-wide view of Caenorhabditis elegans base-substitution mutation processes. Proc. Natl Acad. Sci. USA 106, 16310–16324 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  161. 161

    Cutter, A. D. Multilocus patterns of polymorphism and selection across the X-chromosome of Caenorhabditis remanei. Genetics 178, 1661–1672 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. 162

    Noor, M. A. F. Mutagenesis from meiotic recombination is not a primary driver of sequence divergence between Saccharomyces species. Mol. Biol. Evol. 25, 2439–2444 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. 163

    Connallon, T. & Knowles, L. L. Recombination rate and protein evolution in yeast. BMC Evol. Biol. 7, 235 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. 164

    Weber, C. C. & Hurst, L. D. Protein rates of evolution are predicted by double-strand break events, independent of crossing-over rates. Genome Biol. Evol. 1, 340–349 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. 165

    Kliman, R. M., Irving, N. & Santiago, M. Selection conflicts, gene expression, and codon usage trends in yeast. J. Mol. Evol. 57, 98–109 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. 166

    Dvorak, J., Luo, M. C. & Yang, Z. L. Restriction fragment length polymorphism and divergence in the genomic regions of high and low recombination in self-fertilizing and cross-fertilizing Aegilops species. Genetics 148, 423–434 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. 167

    Schmid, K. J., Ramos-Onsins, S., Ringys-Beckstein, H., Weisshaar, B. & Mitchell-Olds, T. A multilocus sequence survey in Arabidopsis thaliana reveals a genome-wide departure from a neutral model of DNA sequence polymorphism. Genetics 169, 1601–1615 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. 168

    Slotte, T. et al. Genomic determinants of protein evolution and polymorphism in Arabidopsis. Genome Biol. Evol. 3, 1210–1219 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. 169

    Marais, G., Charlesworth, B. & Wright, S. I. Recombination and base composition: the case of the highly self-fertilizing plant Arabidopsis thaliana. Genome Biol. 5, R45 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. 170

    Kraft, T., Sall, T., Magnusson-Rading, I., Nilsson, N. O. & Hallden, C. Positive correlation between recombination rates and levels of genetic variation in natural populations of sea beet (Beta vulgaris subsp. maritima). Genetics 150, 1239–1244 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. 171

    Roselius, K., Stephan, W. & Stadler, T. The relationship of nucleotide polymorphism, recombination rate and selection in wild tomato species. Genetics 171, 753–763 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. 172

    Stephan, W. & Langley, C. H. DNA polymorphism in Lycopersicon and crossing-over per physical length. Genetics 150, 1585–1593 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. 173

    Branca, A. et al. Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in the model legume Medicago truncatula. Proc. Natl Acad. Sci. USA 108, E864–E870 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  174. 174

    Molina, J. et al. Molecular evidence for a single evolutionary origin of domesticated rice. Proc. Natl Acad. Sci. USA 108, 8351–8356 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  175. 175

    Tenaillon, M. I., U'Ren, J., Tenaillon, O. & Gaut, B. S. Selection versus demography: a multilocus investigation of the domestication process in maize. Mol. Biol. Evol. 21, 1214–1225 (2004).

    Article  CAS  Google Scholar 

  176. 176

    Thuillet, A. C. et al. A weak effect of background selection on trinucleotide microsatellites in maize. J. Hered. 99, 45–55 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

A.D.C. is supported by grants from the Natural Sciences and Engineering Research Council of Canada, the US National Institutes of Health (NIH) and a Canada Research Chair. B.A.P. is supported by NIH grant HG004498. We thank L. Loewe and three anonymous reviewers for helpful comments.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Asher D. Cutter.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides

Glossary

Directional selection

Selection that favours one allele over all other alleles of a gene. The frequency of this beneficial allele can rise or can be held in check by recurrent mutations.

Selective interference

When recombination fails to break down linkage disequilibrium between alleles at selected loci, the ability of selection to act on these alleles tends to be reduced.

Selection at linked sites

The interaction between natural selection and genetic linkage that can yield deviations from the levels of polymorphism, allele frequencies and linkage disequilibria expected from neutral evolution alone.

Selective sweep

The increase in frequency of a beneficial allele (and closely linked chromosomal segments by genetic hitch-hiking) to fixation that is caused by positive selection.

Genetic hitch-hiking

The process by which a neutral, or in some cases deleterious, mutations may change in population frequency owing to linkage with a selected mutation.

Site frequency spectrum

The distribution of allele frequencies in a population; it is visualized as the histogram of counts of the number of alleles that have a given population frequency.

Effective population size

(Ne). Formulated by Wright in 1931, Ne reflects the size of an idealized population that would experience drift in the same way as the actual (census) population. Ne can be lower than census population size owing to various factors, including variance in reproductive success, a history of population bottlenecks and inbreeding.

Background selection

The elimination of neutral polymorphisms as a result of their linkage to deleterious mutations that are subject to purifying selection.

Neutral polymorphism

Alternative allelic variants with no selective difference between them, the dynamics of which are mainly controlled by genetic drift and migration. They can, however, be influenced by selection on nearby (linked) loci.

Replacement sites

Also known as nonsynonymous sites, these are any nucleotides within a gene at which a point mutation can alter the encoded amino acid sequence. Models of molecular evolution account for different possible degeneracies of such sites in codons.

d N

The rate of protein-coding sequence divergence that is quantified as the number of nonsynonymous substitutions per nonsynonymous site.

Synonymous sites

Any sites within a gene at which some or all possible point mutations, depending on the degeneracy of the corresponding codon, do not change the encoded amino acid. Changes at synonymous sites are often presumed to be selectively neutral.

Linkage disequilibrium

A measure of whether alleles at two loci coexist in a population in a nonrandom fashion. Alleles that are in linkage disequilibrium are found together on the same haplotype more often than would be expected under free recombination.

McDonald–Kreitman test

A statistical test used to compare between-species divergence and within-species polymorphism at replacement and synonymous sites to infer selection acting on proteins.

Mutation accumulation lines

Unique genetic backgrounds created by multiple generations of controlled breeding in such a way as to minimize the action of natural selection and to maximize the retention of new mutations. They are used to identify spontaneous mutations and to study their phenotypic properties.

Stabilizing selection

A type of natural selection that favours intermediate phenotypes, such as when the population is close to its fitness optimum with respect to the trait.

Genetic draft

Stochastic fluctuations in allele frequencies in a population caused by repeated hard selective sweeps. Hypothesized to be the primary source of stochastic variation in allele frequencies in large populations, in which the sampling effects of genetic drift are relatively weak compared with smaller populations.

Genetic drift

Random fluctuations through time in the allele frequencies of a population caused by a sampling effect that is strongest in small populations. Drift can overwhelm the deterministic effects of natural selection if the selective differences between alleles are small.

Mutation-limited adaptation

When mutational input into a population is sufficiently low, the rate of adaptation will be limited by the input of new beneficial mutations. This common theoretical assumption will be violated in real species with populations that are large, subdivided or subject to frequent changes in selective regime.

Standing genetic variation

Allelic variation that is currently segregating within a population from old mutation events, as opposed to alleles that just arose by new mutation events.

Mutation–drift balance

The equilibrium between input of alleles into a population by mutation and their loss by genetic drift.

Population structure

The distribution of individuals into partially isolated, local subpopulations or demes that are interconnected by migration (gene flow).

Biased gene conversion

(BGC). Gene conversion is a non-reciprocal recombination process that causes one sequence to be overwritten with information from the other. BGC is when the two possible sequences act as donor templates with unequal probabilities.

Muller's ratchet

The irreversible accumulation of deleterious mutations in asexual populations of finite size. The average load of mutations increases over generations because the class of individuals that carry the smallest number of mutant alleles is occasionally lost by genetic drift. In the absence of recombination or compensatory mutation, this class can never be recreated. The process is named after H. J. Muller, who described it in 1964.

Selection coefficient

(s). A parameter describing the difference in average fitness between two genotypes when fitness is measured relative to the average fitness of one of the genotypes (known as the reference genotype).

Genetic architecture

The number, identity, phenotypic effects and population frequencies of the mutations that contribute to phenotypic variation.

Polygenic selection

Selection on a trait that has a genetic basis comprised of many gene loci (tens, hundreds or more). A given strength of selection on the phenotype will exert a weaker effect on any one locus when the trait is polygenic than when the trait is monogenic.

Purifying selection

Natural selection against deleterious alleles that arise in a population, preventing their increase in frequency.

Fitness-class coalescent

A version of structured coalescent models of evolution that traces how individuals descend by mutations through different fitness classes, rather than through time.

Transit time

The duration of time that elapses from when an allele first experiences selection to when it becomes fixed in a population.

F ST

A measure of population subdivision that indicates the proportion of genetic diversity found between populations relative to the amount within populations.

Population bottlenecks

Marked reductions in population size followed by the survival and expansion of a sample of the original population. It often results in the loss of genetic variation and a skewed site frequency spectrum.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cutter, A., Payseur, B. Genomic signatures of selection at linked sites: unifying the disparity among species. Nat Rev Genet 14, 262–274 (2013). https://doi.org/10.1038/nrg3425

Download citation

Further reading

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