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The effect of recombination on background selection*

  • Magnus Nordborg (a1), Brian Charlesworth (a1) and Deborah Charlesworth (a1)

Summary

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.

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Footnotes

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

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References

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Ahn, S., & Tanksley, S. D., (1993). Comparative linkage maps of the rice and maize genomes. Proceedings of the National Academy of Sciences, USA 90, 79807984.
Alexander, M. L., (1976). The genetics of Drosophila virilis. In The Genetics of Drosophila (ed. Ashburner, M. and Novitski, E.). vol. 1c, pp. 13651627. London: Academic Press.
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. 4656. London: Chapman and Hall.
Ashburner, M., (1989). Drosphila. A Laboratory Handbook. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
Barton, N. H., (1994). The reduction in fixation probability caused by substitutions at linked loci. Genetical Research 64, 199208.
Barton, N. H., (1995). Linkage and the limits to natural selection. Genetics 140, 821841.
Berry, A. J., Ajioka, J. W., & Kreitman, M., (1991). Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics 129, 10851098.
Bird, A. P., (1995). Gene number, noise reduction and biological complexity. Trends in Genetics 11, 77117.
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, 64146418.
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, 783796.
Caballero, A., (1995). On the effective size of populations with separate sexes, with particular reference to sexlinked genes. Genetics 139, 10071011.
Charlesworth, B., (1990). Mutation—selection balance and the evolutionary advantage of sex and recombination. Genetical Research 55, 199221.
Charlesworth, B., (1994). The effect of background selection against deleterious mutations on weakly selected, linked variants. Genetial Research 63, 213227.
Charlesworth, B., Charlesworth, D., & Morgan, M. T., (1990). Genetic loads and estimates of mutation rates in highly inbred plant populations. Nature 347, 380382.
Charlesworth, B., Charlesworth, D., & Morgan, M. T., (1991). Multilocus models of inbreeding depression with synergistic selection and partial self-fertilisation. Genetical Research 57, 177194.
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, 103114.
Charlesworth, B., Morgan, M. T., & Charlesworth, D., (1993). The effect of deleterious mutations on neutral molecular variation. Genetics 134, 12891303.
Charlesworth, D., Charlesworth, B., & Morgan, M. T., (1995). The pattern of neutral molecular variation under the background selection model. Genetics 141, 16191632.
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, 209214.
Crow, J. F., (1970). Genetic loads and the cost of natural selection. In Mathematical Topics in Population Genetics (ed. Kojima, K.). pp. 128177. Berlin: Springer-Verlag.
Crow, J. F., & Kimura, M., (1970). An Introduction to Population Genetics Theory. New York: Harper & Row.
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. 135. London: Academic Press.
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, 423447.
Ewens, W. J., (1979). Mathematical Population Genetics. Berlin: Springer-Verlag.
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, 48384841.
Felsenstein, J., (1965). The effect of linkage on directional selection. Genetics 52, 349363.
Felsenstein, J., & Yokoyama, S., (1976). The evolutionary advantage of recombination. II. Individual selection for recombination. Genetics 83, 845859.
Free Software Foundation (1992). GNU C + + Library. Publicly available via ftp://prep.ai.mit.edu/.
Gillespie, J. H., (1994). Alternatives to the neutral theory. In Non-Neutral Evolution: Theories and Molecular Data (ed. Golding, G. B.). pp. 117. London: Chapman and Hall.
Haldane, J. B. S., (1919). The combination of linkage values and the calculation of distance between loci of linked factors. Journal of Genetics 8, 299309.
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, 838844.
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, 68156818.
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. 140153. New York: Chapman & Hall.
Hudson, R. R., & Kaplan, N. L., (1995). Deleterious background selection with recombination. Genetics 141, 16051617.
Johnston, M. O., & Schoen, D. J., (1995). Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species. Science 267, 226229.
Kaplan, N. L., Hudson, R. R., & Langley, C. H., (1989). The ‘hitch-hiking’ effect revisited. Genetics 123, 887899.
Keightley, P. D., (1994). The distribution of mutation effects on viability in Drosophila melanogaster. Genetics 138, 13151322.
Kimura, M., (1969). The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics 61, 893903.
Kimura, M., & Maruyama, T., (1966). The mutational load with epistatic gene interactions in fitness. Genetics 54, 13371351.
Kimura, M., & Ohta, T., (1969). The average number of generations until extinction of an individual mutant gene in a population. Genetics 63, 701709.
Kimura, M., & Ohta, T., (1971). Theoretical Aspects of Population Genetics. Princeton: Princeton University Press.
Kliman, R. M., & Hey, J., (1993). Reduced natural selection associated with low recombination in Drosophila melanogaster. Molecular Biology and Evolution 10, 12391258.
Kondrashov, A. S., (1988). Deleterious mutations and the evolution of sexual reproduction. Nature 336, 435440.
Kondrashov, A. S., & Crow, J. F., (1993). A molecular approach to estimating the human deleterious mutation rate. Human Mutation 2, 229234.
Kosambi, D. D., (1944). The estimation of map distance from recombination values. Annals of Eugenics 12, 172175.
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. 157184. Basel: Birkhäuser.
Krimbas, C. B., (1993). Drosophila subobscura. Hamburg: Verlag Dr Kovač.
Lande, R., (1994). Risk of population extinction from fixation of new deleterious mutations. Evolution 48, 14601469.
Smith, J. Maynard, & Haigh, J., (1974). The hitchhiking effect of a favourable gene. Genetical Research 23, 2335.
McPeek, M. S., & Speed, T. P., (1995). Modeling interference in genetic recombination. Genetics 139, 10311044.
Morton, N. E., (1991). Parameters of the human genome. Proceedings of the National Academy of Sciences, USA 88, 74747476.
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, 11951208.
Mukai, T., & Yamaguchi, O., (1974). The genetic structure of natural populations of Drosophila melanogaster. XI. Genetic variability in a local population. Genetics 76, 339366.
Nagylaki, T., (1995). The inbreeding effective population number in dioecious populations. Genetics 139, 473485.
Nei, M., (1987). Molecular Evolutionary Genetics. New York: Columbia University Press.
Nei, M., & Murata, M., (1966). Effective population size when fertility is inherited. Genetical Research 8, 257260.
Neuffer, M. G., & Coe, E. H., (1974). Corn (maize). In Handbook of Genetics (ed. King, R. C.). vol. 2, pp. 330. New York: Plenum.
NIH/CEPH Collaborative Mapping Group (1992). A comprehensive genetic linkage map of the human genome. Science 258, 6786.
Ohta, T., & Kimura, M., (1969). Linkage disequilibrium due to random genetic drift. Genetical Research 13, 4755.
Ohta, T., & Kimura, M., (1975). The effect of a selected locus on heterozygosity of neutral alleles (the hitch-hiking effect). Genetical Research 25, 313326.
Robertson, A., (1961). Inbreeding in artificial selection programmes. Genetical Research 2, 189194.
Santiago, E., & Caballero, A., (1995). Effective size of populations under selection. Genetics 139, 10131030.
Simonsen, K. L., Churchill, G. A., & Aquadro, C. F., (1995). Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141, 413429.
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, 959962.
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, 237254.
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, 11411160.
Thomson, G., (1977). The effect of a selected locus on linked neutral loci. Genetics 85, 753788.
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, 842854.

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