Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-26T17:46:33.309Z Has data issue: false hasContentIssue false

The effect of background selection against deleterious mutations on weakly selected, linked variants

Published online by Cambridge University Press:  14 April 2009

Brian Charlesworth
Affiliation:
Department of Ecology and Evolution, The University of Chicago, 1101 E. 57th St., Chicago, IL 60637-1573, USA
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

This paper analyses the effects of selection against deleterious alleles maintained by mutation (‘ background selection’) on rates of evolution and levels of genetic diversity at weakly selected, completely linked, loci. General formulae are derived for the expected rates of gene substitution and genetic diversity, relative to the neutral case, as a function of selection and dominance coefficients at the loci in question, and of the frequency of gametes that are free of deleterious mutations with respect to the loci responsible for background selection. As in the neutral case, most effects of background selection can be predicted by considering the effective size of the population to be multiplied by the frequency of mutation-free gametes. Levels of genetic diversity can be sharply reduced by background selection, with the result that values for sites under selection approach those for neutral variants subject to the same regime of background selection. Rates of fixation of slightly deleterious mutations are increased by background selection, and rates of fixation of advantageous mutations are reduced. The properties of sex-linked and autosomal asexual and self-fertilizing populations are considered. The implications of these results for the interpretation of studies of molecular evolution and variation are discussed.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1994

References

Aguade, M., Meyers, W., Long, A. D. & Langley, C. H. (1994). Reduced DNA sequence polymorphism in the su(s) and su(wa) regions of Drosophila melanogaster as revealed by SSCP and stratified DNA sequencing. Proceedings of the National Academy of Sciences, USA (in press).CrossRefGoogle ScholarPubMed
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.), in press. London: Chapman & Hall.Google Scholar
Ashburner, M. (1989). Drosophila. A Laboratory Handbook. Cold Spring Harbor N.Y.: Cold Spring Harbor Laboratory Press.Google Scholar
Begun, D. J. & Aquadro, C. F. (1992). Levels of naturally occurring DNA polymorphism correlate with recombination rate in D. melanogaster. Nature 356, 519520.CrossRefGoogle ScholarPubMed
Begun, D. J. & Aquadro, C. F. (1993). African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature 365, 548550.CrossRefGoogle ScholarPubMed
Bell, G. (1982). The Masterpiece of Nature. London: Croom-Helm.Google Scholar
Berry, A. J., Ajioka, J. W. & Kreitman, M. (1991). Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics 129, 11111117.CrossRefGoogle ScholarPubMed
Birky, C. W. & Walsh, J. B. (1988). Effects of linkage on rates of molecular evolution. Proceedings of the National Academy of Sciences, USA 85, 64146418.CrossRefGoogle ScholarPubMed
Bulmer, M. G. (1991). The selection-mutation-drift theory of synonymous codon usage. Genetics 129, 897907.CrossRefGoogle ScholarPubMed
Charlesworth, B. (1992). Evolutionary rates in partially selffertilizing species. American Naturalist 140, 126148.CrossRefGoogle ScholarPubMed
Charlesworth, B. (1993). More mutations in males. Current Biology 3, 466467.CrossRefGoogle ScholarPubMed
Charlesworth, B. (1994). Patterns in the genome. Current Biology 4, 182184.CrossRefGoogle ScholarPubMed
Charlesworth, B., Coyne, J. A. & Barton, N. H. (1987). The relative rates of evolution of sex chromosomes and autosomes. American Naturalist 130, 113146.CrossRefGoogle Scholar
Charlesworth, B., Morgan, M. T. & Charlesworth, D. (1993). The effect of deleterious mutations on neutral molecular variation. Genetics 134, 12891303.CrossRefGoogle ScholarPubMed
Crow, J. F. (1993). How much do we know about spontaneous human mutation rates? Environmental and Molecular Mutagenesis 21, 122129.CrossRefGoogle ScholarPubMed
Crow, J. F. & Simmons, M. J. (1983). The mutation load in Drosophila. In The Genetics and Biology of Drosophila (ed. Ashburner, M., Carson, H. L., and Thomson, J. N.), pp. 135. London: Academic Press.Google Scholar
Ewens, W. J. (1979). Mathematical Population Genetics. Berlin: Springer-Verlag.Google Scholar
Gillespie, J. H. (1991). The Causes of Molecular Evolution. Oxford: Oxford University Press.Google Scholar
Houle, D., Hoffmaster, D. K., Assimacopoulos, S. & Charlesworth, B. (1992). The genomic mutation rate for fitness in Drosophila. Nature 359, 5860.CrossRefGoogle ScholarPubMed
Hudson, R. R. (1994). Gene trees with background selection. In Non-neutral Evolution: Theories and Molecular Data (ed. Golding, G. B.), in press. London: Chapman & Hall.Google Scholar
Hudson, R. R., Kreitman, M. & Aguade, M. (1987). A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153159.CrossRefGoogle ScholarPubMed
Ikemura, I. & Wada, K. (1991). Evident diversity of codon usage patterns of human genes with respect to chromosome banding patterns and chromosome numbers; relation between nucleotide sequence data and cytogenetic data. Nucleic Acids Research 19, 43334339.CrossRefGoogle ScholarPubMed
Kaplan, N. L., Hudson, R. R. & Langley, C. H. (1989). The ‘hitch-hiking’ effect revisited. Genetics 123, 887899.CrossRefGoogle Scholar
Kimura, M. (1962). On the probability of fixation of a mutant gene in a population. Genetics 47, 713719.CrossRefGoogle ScholarPubMed
Kimura, M. (1969). The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics 61, 893903.CrossRefGoogle Scholar
Kimura, M. (1971). Theoretical foundations of population genetics at the molecular level. Theoretical Population Biology 2, 174208.CrossRefGoogle ScholarPubMed
Kimura, M. (1983). The Neutral Theory of Molecular Evolution. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
Kimura, M. & Ohta, T. (1971). Theoretical Aspects of Population Genetics. Princeton, NJ: 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, 12391258.Google ScholarPubMed
Kondrashov, A. S. (1988). Deleterious mutations and the evolution of sexual reproduction. Nature 336, 435440.CrossRefGoogle ScholarPubMed
Kreitman, M. (1991). Detecting selection at the level of DNA. In Evolution at the Molecular Level (ed. Selander, R. K., Clark, A. G., and Whittam, T. S.), pp. 202221. Sunderland, MA: Sinauer.Google Scholar
Kreitman, M. & Aguadé, M. (1986). Excess polymorphism at the alcohol dehydrogenase locus in Drosophila melanogaster. Genetics 114, 93110.CrossRefGoogle ScholarPubMed
Kreitman, M. & Hudson, R. R. (1991). Inferring the evolutionary history of the Adh and Adh-dup loci in Drosophila melanogaster from patterns of polymorphism and divergence. Genetics 127, 565582.CrossRefGoogle ScholarPubMed
Li, W.-H. & Graur, D. (1991). Fundamentals of Molecular Evolution. Sunderland, MA: Sinauer.Google Scholar
Lindsley, D. L. & Zimm, G. G. (1992). The Genome of Drosophila melanogaster. San Diego, CA: Academic Press.Google Scholar
Smith, J. Maynard (1978). The Evolution of Sex. Cambridge: Cambridge University Press.Google Scholar
Smith, J. Maynard & Haigh, J. (1974). The hitch-hiking effect of a favourable gene. Genetical Research 23, 2335.CrossRefGoogle ScholarPubMed
McDonald, I. H. & Kreitman, M. (1991). Accelerated protein evolution at the Adh locus in Drosophila. Nature 351, 652654.CrossRefGoogle Scholar
Miyata, T., Hayashida, H., Kuma, K., Mitsuyasu, K. & Yasunaga, T. (1987). Male-driven molecular evolution: a model and nucleotide sequence analysis. Cold Spring Harbor Symposia on Quantitative Biology 52, 863867.CrossRefGoogle Scholar
Mukai, T., Chigusa, S. I., Mettler, L. E. & Crow, J. F. (1972). Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics 72, 335355.CrossRefGoogle ScholarPubMed
O'Brien, S. J. (1993). The genomics generation. Current Biology 3, 395397.CrossRefGoogle Scholar
Ohta, T. (1974). Mutational pressure as main cause of molecular evolution. Nature 252, 351354.CrossRefGoogle Scholar
Ohta, T. (1992). The nearly neutral theory of molecular evolution. Annual Review of Ecology and Systematics 23, 263286.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, 313326.CrossRefGoogle ScholarPubMed
Pollak, E. (1987). On the theory of partially inbreeding populations. I. Partial selfing. Genetics 117, 353360.CrossRefGoogle ScholarPubMed
Sawyer, S. A. & Hartl, D. L. (1992). Population genetics of polymorphism and divergence. Genetics 132, 11611176.CrossRefGoogle ScholarPubMed
Stephan, W. & Mitchell, S. J. (1992). Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae. Genetics 132, 10391045.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Tajima, F. (1989). Statistical method for testing the neutral mutation hypothesis. Genetics 123, 585595.CrossRefGoogle ScholarPubMed
Thomson, G. (1977). The effect of a selected locus on linked neutral loci. Genetics 85, 753788.CrossRefGoogle ScholarPubMed
Wiehe, T. H. E. & Stephan, W. (1993). Analysis of a genetic hitchhiking model and its application to DNA polymorphism data from Drosophila melanogaster. Molecular Biology and Evolution 10, 842854.Google ScholarPubMed
Woodruff, R. C., Slatko, B. E. & Thompson, J. N. (1983). Factors affecting mutation rates in natural populations. In The Genetics and Biology of Drosophila, Vol. 3c (ed. Ashburner, M., Carson, H. L., and Thompson, J. N.), pp. 37124. London: Academic Press.Google Scholar
Wright, S. (1969). Evolution and the Genetics of Populations. Chicago, IL: University of Chicago Press.Google Scholar