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The effect of recombination on background selection*

Published online by Cambridge University Press:  14 April 2009

Magnus Nordborg ,
Brian Charlesworth  and
Deborah Charlesworth
Magnus Nordborg*
Affiliation:
Department of Ecology & Evolution, The University of Chicago, 1101 E. 57th St, Chicago, IL 60637-1573, USA. Tel: (312) 702-1040, Fax: (312) 702-9740, E-mail: [email protected]
Brian Charlesworth
Affiliation:
Department of Ecology & Evolution, The University of Chicago, 1101 E. 57th St, Chicago, IL 60637-1573, USA. Tel: (312) 702-1040, Fax: (312) 702-9740, E-mail: [email protected]
Deborah Charlesworth
Affiliation:
Department of Ecology & Evolution, The University of Chicago, 1101 E. 57th St, Chicago, IL 60637-1573, USA. Tel: (312) 702-1040, Fax: (312) 702-9740, E-mail: [email protected]
*
† Corresponding author.
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Summary

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An approximate equation is derived, which predicts the effect on variability at a neutral locus of background selection due to a set of partly linked deleterious mutations. Random mating, multiplicative fitnesses, and sufficiently large population size that the selected loci are in mutation/selection equilibrium are assumed. Given these assumptions, the equation is valid for an arbitrary genetic map, and for an arbitrary distribution of selection coefficients across loci. Monte Carlo computer simulations show that the formula performs well for small population sizes under a wide range of conditions, and even seems to apply when there are epistatic fitness interactions among the selected loci. Failure occurred only with very weak selection and tight linkage. The formula is shown to imply that weakly selected mutations are more likely than strongly selected mutations to produce regional patterning of variability along a chromosome in response to local variation in recombination rates. Loci at the extreme tip of a chromosome experience a smaller effect of background selection than loci closer to the centre. It is shown that background selection can produce a considerable overall reduction in variation in organisms with small numbers of chromosomes and short maps, such as Drosophila. Large overall effects are less likely in species with higher levels of genetic recombination, such as mammals, although local reductions in regions of reduced recombination might be detectable.

Type
Research Article
Information
Genetics Research , Volume 67 , Issue 2 , April 1996 , pp. 159 - 174
Copyright
Copyright © Cambridge University Press 1996

Footnotes

*

This paper is dedicated to Richard Lewontin on the occasion of his 65th birthday.

References

Ahn, S., & Tanksley, S. D., (1993). Comparative linkage maps of the rice and maize genomes. Proceedings of the National Academy of Sciences, USA 90, 7980–7984.Google Scholar
Alexander, M. L., (1976). The genetics of Drosophila virilis. In The Genetics of Drosophila (ed. Ashburner, M. and Novitski, E.). vol. 1c, pp. 1365–1627. London: Academic Press.Google Scholar
Aquadro, C. F., Begun, D. J., & Kindahl, E. C., (1994). Selection, recombination, and DNA polymorphism in Drosophila. In Non-Neutral Evolution: Theories and Molecular Data (ed. Golding, G. B.). pp. 46–56. London: Chapman and Hall.CrossRefGoogle Scholar
Ashburner, M., (1989). Drosphila. A Laboratory Handbook. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.Google Scholar
Barton, N. H., (1994). The reduction in fixation probability caused by substitutions at linked loci. Genetical Research 64, 199–208.CrossRefGoogle Scholar
Barton, N. H., (1995). Linkage and the limits to natural selection. Genetics 140, 821–841.CrossRefGoogle ScholarPubMed
Berry, A. J., Ajioka, J. W., & Kreitman, M., (1991). Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics 129, 1085–1098.CrossRefGoogle ScholarPubMed
Bird, A. P., (1995). Gene number, noise reduction and biological complexity. Trends in Genetics 11, 77–117.CrossRefGoogle ScholarPubMed
Birky, C. W. Jr, & Walsh, J. B., (1988). Effects of linkage on rates of molecular evolution. Proceedings of the National Academy of Sciences, USA 85, 6414–6418.CrossRefGoogle ScholarPubMed
Braverman, J. M., Hudson, R. R., Kaplan, N. L., Langley, C. H., & Stephan, W., (1995). The hitchhiking effect on the site frequency spectrum of DNA polymorphism. Genetics 140, 783–796.Google Scholar
Caballero, A., (1995). On the effective size of populations with separate sexes, with particular reference to sexlinked genes. Genetics 139, 1007–1011.CrossRefGoogle ScholarPubMed
Charlesworth, B., (1990). Mutation—selection balance and the evolutionary advantage of sex and recombination. Genetical Research 55, 199–221.CrossRefGoogle ScholarPubMed
Charlesworth, B., (1994). The effect of background selection against deleterious mutations on weakly selected, linked variants. Genetial Research 63, 213–227.CrossRefGoogle ScholarPubMed
Charlesworth, B., Charlesworth, D., & Morgan, M. T., (1990). Genetic loads and estimates of mutation rates in highly inbred plant populations. Nature 347, 380–382.CrossRefGoogle Scholar
Charlesworth, B., Charlesworth, D., & Morgan, M. T., (1991). Multilocus models of inbreeding depression with synergistic selection and partial self-fertilisation. Genetical Research 57, 177–194.CrossRefGoogle Scholar
Charlesworth, B., Lapid, A., & Canada, D., (1992). The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. I. Element frequencies and distribution. Genetical Research 60, 103–114.CrossRefGoogle Scholar
Charlesworth, B., Morgan, M. T., & Charlesworth, D., (1993). The effect of deleterious mutations on neutral molecular variation. Genetics 134, 1289–1303.CrossRefGoogle ScholarPubMed
Charlesworth, D., Charlesworth, B., & Morgan, M. T., (1995). The pattern of neutral molecular variation under the background selection model. Genetics 141, 1619–1632.CrossRefGoogle ScholarPubMed
Charlesworth, D., Lyons, E. E., & Litchfield, L. B., (1994). Inbreeding depression in two highly inbreeding populations of Leavenworthia. Proceedings of the Royal Society, London, B 258, 209–214.Google Scholar
Crow, J. F., (1970). Genetic loads and the cost of natural selection. In Mathematical Topics in Population Genetics (ed. Kojima, K.). pp. 128–177. Berlin: Springer-Verlag.CrossRefGoogle Scholar
Crow, J. F., & Kimura, M., (1970). An Introduction to Population Genetics Theory. New York: Harper & Row.Google Scholar
Crow, J. F., & Simmons, M. J., (1983). The mutation load in Drosophila. In The Genetics and Biology of Drosophila (ed. Carson, H. L., Ashburner, M. and Thomson, J. N.). vol. 3e, pp. 1–35. London: Academic Press.Google Scholar
Dietrich, W., Katz, H., Lincoln, S. E., Shin, H.-S., Friedman, J., Dracopoli, N. C., & Lander, E. S., (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.CrossRefGoogle ScholarPubMed
Ewens, W. J., (1979). Mathematical Population Genetics. Berlin: Springer-Verlag.Google Scholar
Feldman, M. W., Christiansen, F. B., & Brooks, L. D., (1980). Evolution of recombination in a constant environment. Proceedings of the National Academy of Sciences, USA 77, 4838–4841.CrossRefGoogle Scholar
Felsenstein, J., (1965). The effect of linkage on directional selection. Genetics 52, 349–363.CrossRefGoogle ScholarPubMed
Felsenstein, J., & Yokoyama, S., (1976). The evolutionary advantage of recombination. II. Individual selection for recombination. Genetics 83, 845–859.CrossRefGoogle ScholarPubMed
Free Software Foundation (1992). GNU C + + Library. Publicly available via ftp://prep.ai.mit.edu/.Google Scholar
Gillespie, J. H., (1994). Alternatives to the neutral theory. In Non-Neutral Evolution: Theories and Molecular Data (ed. Golding, G. B.). pp. 1–17. London: Chapman and Hall.Google Scholar
Haldane, J. B. S., (1919). The combination of linkage values and the calculation of distance between loci of linked factors. Journal of Genetics 8, 299–309.Google Scholar
Haldane, J. B. S., (1927). A mathematical theory of natural and artifical selection. Part V. Selection and mutation. Proceedings of the Cambridge Philosophical Society 23, 838–844.CrossRefGoogle Scholar
Hudson, R. R., (1994). How can the low levels of Drosophila sequence variation in regions of the genome with low levels of recombination be explained?. Proceedings of the National Academy of Sciences, USA 91, 6815–6818.CrossRefGoogle ScholarPubMed
Hudson, R. R., & Kaplan, N. L., (1994). Gene trees with background selection. In Non-Neutral Evolution: Theories and Molecular Data (ed. Golding, G. B.). pp. 140–153. New York: Chapman & Hall.CrossRefGoogle Scholar
Hudson, R. R., & Kaplan, N. L., (1995). Deleterious background selection with recombination. Genetics 141, 1605–1617.CrossRefGoogle ScholarPubMed
Johnston, M. O., & Schoen, D. J., (1995). Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species. Science 267, 226–229.CrossRefGoogle ScholarPubMed
Kaplan, N. L., Hudson, R. R., & Langley, C. H., (1989). The ‘hitch-hiking’ effect revisited. Genetics 123, 887–899.CrossRefGoogle Scholar
Keightley, P. D., (1994). The distribution of mutation effects on viability in Drosophila melanogaster. Genetics 138, 1315–1322.CrossRefGoogle ScholarPubMed
Kimura, M., (1969). The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics 61, 893–903.CrossRefGoogle Scholar
Kimura, M., & Maruyama, T., (1966). The mutational load with epistatic gene interactions in fitness. Genetics 54, 1337–1351.CrossRefGoogle ScholarPubMed
Kimura, M., & Ohta, T., (1969). The average number of generations until extinction of an individual mutant gene in a population. Genetics 63, 701–709.CrossRefGoogle Scholar
Kimura, M., & Ohta, T., (1971). Theoretical Aspects of Population Genetics. Princeton: Princeton University Press.Google ScholarPubMed
Kliman, R. M., & Hey, J., (1993). Reduced natural selection associated with low recombination in Drosophila melanogaster. Molecular Biology and Evolution 10, 1239–1258.Google ScholarPubMed
Kondrashov, A. S., (1988). Deleterious mutations and the evolution of sexual reproduction. Nature 336, 435–440.Google Scholar
Kondrashov, A. S., & Crow, J. F., (1993). A molecular approach to estimating the human deleterious mutation rate. Human Mutation 2, 229–234.CrossRefGoogle ScholarPubMed
Kosambi, D. D., (1944). The estimation of map distance from recombination values. Annals of Eugenics 12, 172–175.CrossRefGoogle Scholar
Kreitman, M., & Wayne, M. L., (1994). Organization of genetic variation at the molecular level: lessons from Drosophila. In Molecular Ecology and Evolution: Approaches and Applications (ed. Schierwater, B., Streit, B., Wagner, G. P. and DeSalle, R.). pp. 157–184. Basel: Birkhäuser.Google Scholar
Krimbas, C. B., (1993). Drosophila subobscura. Hamburg: Verlag Dr Kovač.Google Scholar
Lande, R., (1994). Risk of population extinction from fixation of new deleterious mutations. Evolution 48, 1460–1469.CrossRefGoogle ScholarPubMed
Smith, J. Maynard, & Haigh, J., (1974). The hitchhiking effect of a favourable gene. Genetical Research 23, 23–35.CrossRefGoogle ScholarPubMed
McPeek, M. S., & Speed, T. P., (1995). Modeling interference in genetic recombination. Genetics 139, 1031–1044.Google Scholar
Morton, N. E., (1991). Parameters of the human genome. Proceedings of the National Academy of Sciences, USA 88, 7474–7476.CrossRefGoogle ScholarPubMed
Mukai, T., Cardellino, R. K., Watanabe, T. K., & Crow, J. F., (1974). The genetic variance for viability and its components in a population of Drosophila melanogaster. Genetics 76, 1195–1208.CrossRefGoogle Scholar
Mukai, T., & Yamaguchi, O., (1974). The genetic structure of natural populations of Drosophila melanogaster. XI. Genetic variability in a local population. Genetics 76, 339–366.CrossRefGoogle Scholar
Nagylaki, T., (1995). The inbreeding effective population number in dioecious populations. Genetics 139, 473–485.CrossRefGoogle ScholarPubMed
Nei, M., (1987). Molecular Evolutionary Genetics. New York: Columbia University Press.CrossRefGoogle Scholar
Nei, M., & Murata, M., (1966). Effective population size when fertility is inherited. Genetical Research 8, 257–260.CrossRefGoogle ScholarPubMed
Neuffer, M. G., & Coe, E. H., (1974). Corn (maize). In Handbook of Genetics (ed. King, R. C.). vol. 2, pp. 3–30. New York: Plenum.Google Scholar
NIH/CEPH Collaborative Mapping Group (1992). A comprehensive genetic linkage map of the human genome. Science 258, 67–86.Google Scholar
Ohta, T., & Kimura, M., (1969). Linkage disequilibrium due to random genetic drift. Genetical Research 13, 47–55.CrossRefGoogle Scholar
Ohta, T., & Kimura, M., (1975). The effect of a selected locus on heterozygosity of neutral alleles (the hitch-hiking effect). Genetical Research 25, 313–326.CrossRefGoogle ScholarPubMed
Robertson, A., (1961). Inbreeding in artificial selection programmes. Genetical Research 2, 189–194.Google Scholar
Santiago, E., & Caballero, A., (1995). Effective size of populations under selection. Genetics 139, 1013–1030.Google Scholar
Simonsen, K. L., Churchill, G. A., & Aquadro, C. F., (1995). Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141, 413–429.Google Scholar
Stephan, W., (1995). An improved method for estimating the rate of fixation of favorable mutations based on DNA polymorphism data. Molecular Biology and Evolution 12, 959–962.Google Scholar
Stephan, W., Wiehe, T. H. E., & Lenz, M. W., (1992). The effect of strongly selected substitutions on neutral polymorphism: analytical results based on diffusion theory. Theoretical Population Biology 41, 237–254.Google Scholar
Tanksley, S. D., Ganal, M. W., Prince, J. P., deVicente, M. C., Bonierbale, M. W., Broun, P., Fulton, T. M., Giovannoni, J. J., Grandillo, S., Martin, G. B., Messeguer, R., Miller, J. C., Miller, L., Paterson, A. H., Pineda, O., Roder, M. S., Wing, R. A., Wu, W., & Young, N. D., (1992). High density molecular linkage maps of the tomato and potato genomes. Genetics 132, 1141–1160.CrossRefGoogle ScholarPubMed
Thomson, G., (1977). The effect of a selected locus on linked neutral loci. Genetics 85, 753–788.CrossRefGoogle ScholarPubMed
Wiehe, T. H. E., & Stephan, W., (1993). Analysis of a genetic hitchhiking model and its application to DNA polymorphism data. Molecular Biology and Evolution 10, 842–854.Google Scholar