Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1993 Aug;134(4):1289–1303. doi: 10.1093/genetics/134.4.1289

The Effect of Deleterious Mutations on Neutral Molecular Variation

B Charlesworth 1, M T Morgan 1, D Charlesworth 1
PMCID: PMC1205596  PMID: 8375663

Abstract

Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguade M., Miyashita N., Langley C. H. Reduced variation in the yellow-achaete-scute region in natural populations of Drosophila melanogaster. Genetics. 1989 Jul;122(3):607–615. doi: 10.1093/genetics/122.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beech R. N., Brown A. J. Insertion-deletion variation at the yellow-achaete-scute region in two natural populations of Drosophila melanogaster. Genet Res. 1989 Feb;53(1):7–15. doi: 10.1017/s0016672300027804. [DOI] [PubMed] [Google Scholar]
  3. Begun D. J., Aquadro C. F. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. doi: 10.1038/356519a0. [DOI] [PubMed] [Google Scholar]
  4. Begun D. J., Aquadro C. F. Molecular population genetics of the distal portion of the X chromosome in Drosophila: evidence for genetic hitchhiking of the yellow-achaete region. Genetics. 1991 Dec;129(4):1147–1158. doi: 10.1093/genetics/129.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berry A. J., Ajioka J. W., Kreitman M. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics. 1991 Dec;129(4):1111–1117. doi: 10.1093/genetics/129.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Charlesworth B. Evolutionary biology. New genes sweep clean. Nature. 1992 Apr 9;356(6369):475–476. doi: 10.1038/356475a0. [DOI] [PubMed] [Google Scholar]
  7. Charlesworth B., Lapid A., Canada D. The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. II. Inferences on the nature of selection against elements. Genet Res. 1992 Oct;60(2):115–130. doi: 10.1017/s0016672300030809. [DOI] [PubMed] [Google Scholar]
  8. Charlesworth B. Mutation-selection balance and the evolutionary advantage of sex and recombination. Genet Res. 1990 Jun;55(3):199–221. doi: 10.1017/s0016672300025532. [DOI] [PubMed] [Google Scholar]
  9. Charlesworth D., Morgan M. T., Charlesworth B. The effect of linkage and population size on inbreeding depression due to mutational load. Genet Res. 1992 Feb;59(1):49–61. doi: 10.1017/s0016672300030160. [DOI] [PubMed] [Google Scholar]
  10. Eanes W. F., Labate J., Ajioka J. W. Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster. Mol Biol Evol. 1989 Sep;6(5):492–502. doi: 10.1093/oxfordjournals.molbev.a040565. [DOI] [PubMed] [Google Scholar]
  11. Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. doi: 10.1093/genetics/78.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Felsenstein J., Yokoyama S. The evolutionary advantage of recombination. II. Individual selection for recombination. Genetics. 1976 Aug;83(4):845–859. doi: 10.1093/genetics/83.4.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haigh J. The accumulation of deleterious genes in a population--Muller's Ratchet. Theor Popul Biol. 1978 Oct;14(2):251–267. doi: 10.1016/0040-5809(78)90027-8. [DOI] [PubMed] [Google Scholar]
  14. Hedrick P. W. Hitchhiking: a comparison of linkage and partial selfing. Genetics. 1980 Mar;94(3):791–808. doi: 10.1093/genetics/94.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Houle D., Hoffmaster D. K., Assimacopoulos S., Charlesworth B. The genomic mutation rate for fitness in Drosophila. Nature. 1992 Sep 3;359(6390):58–60. doi: 10.1038/359058a0. [DOI] [PubMed] [Google Scholar]
  16. KIMURA M., MARUYAMA T., CROW J. F. THE MUTATION LOAD IN SMALL POPULATIONS. Genetics. 1963 Oct;48:1303–1312. doi: 10.1093/genetics/48.10.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaplan N. L., Hudson R. R., Langley C. H. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. doi: 10.1093/genetics/123.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kimura M., Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. doi: 10.1093/genetics/54.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kimura M., Ohta T. The Average Number of Generations until Fixation of a Mutant Gene in a Finite Population. Genetics. 1969 Mar;61(3):763–771. doi: 10.1093/genetics/61.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kimura M., Ota T. The average number of generations until extinction of an individual mutant gene in a finite population. Genetics. 1969 Nov;63(3):701–709. doi: 10.1093/genetics/63.3.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura M. The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics. 1969 Apr;61(4):893–903. doi: 10.1093/genetics/61.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kimura M. Theoretical foundation of population genetics at the molecular level. Theor Popul Biol. 1971 Jun;2(2):174–208. doi: 10.1016/0040-5809(71)90014-1. [DOI] [PubMed] [Google Scholar]
  23. Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
  24. Langley C. H., MacDonald J., Miyashita N., Aguadé M. Lack of correlation between interspecific divergence and intraspecific polymorphism at the suppressor of forked region in Drosophila melanogaster and Drosophila simulans. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1800–1803. doi: 10.1073/pnas.90.5.1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Martín-Campos J. M., Comerón J. M., Miyashita N., Aguadé M. Intraspecific and interspecific variation at the y-ac-sc region of Drosophila simulans and Drosophila melanogaster. Genetics. 1992 Apr;130(4):805–816. doi: 10.1093/genetics/130.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maruyama T., Fuerst P. A. Population bottlenecks and nonequilibrium models in population genetics. I. Allele numbers when populations evolve from zero variability. Genetics. 1984 Nov;108(3):745–763. doi: 10.1093/genetics/108.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Maruyama T., Fuerst P. A. Population bottlenecks and nonequilibrium models in population genetics. II. Number of alleles in a small population that was formed by a recent bottleneck. Genetics. 1985 Nov;111(3):675–689. doi: 10.1093/genetics/111.3.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McCracken G. F., Selander R. K. Self-fertilization and monogenic strains in natural populations of terrestrial slugs. Proc Natl Acad Sci U S A. 1980 Jan;77(1):684–688. doi: 10.1073/pnas.77.1.684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Miyashita N. T. Molecular and phenotypic variation of the Zw locus region in Drosophila melanogaster. Genetics. 1990 Jun;125(2):407–419. doi: 10.1093/genetics/125.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mukai T., Chigusa S. I., Mettler L. E., Crow J. F. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. doi: 10.1093/genetics/72.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pollak E. On the theory of partially inbreeding finite populations. I. Partial selfing. Genetics. 1987 Oct;117(2):353–360. doi: 10.1093/genetics/117.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stephan W., Mitchell S. J. Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae. Genetics. 1992 Dec;132(4):1039–1045. doi: 10.1093/genetics/132.4.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sved J. A. Heterosis at the level of the chromosome and at the level of the gene. Theor Popul Biol. 1972 Dec;3(4):491–506. doi: 10.1016/0040-5809(72)90019-6. [DOI] [PubMed] [Google Scholar]
  34. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tajima F. The effect of change in population size on DNA polymorphism. Genetics. 1989 Nov;123(3):597–601. doi: 10.1093/genetics/123.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Thomson G. The effect of a selected locus on linked neutral loci. Genetics. 1977 Apr;85(4):753–788. doi: 10.1093/genetics/85.4.753. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES