• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Aug 1993; 134(4): 1289–1303.
PMCID: PMC1205596

The Effect of Deleterious Mutations on Neutral Molecular Variation

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 (1.5M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aguade M, Miyashita N, Langley CH. Reduced variation in the yellow-achaete-scute region in natural populations of Drosophila melanogaster. Genetics. 1989 Jul;122(3):607–615. [PMC free article] [PubMed]
  • Beech RN, Brown AJ. Insertion-deletion variation at the yellow-achaete-scute region in two natural populations of Drosophila melanogaster. Genet Res. 1989 Feb;53(1):7–15. [PubMed]
  • Begun DJ, Aquadro CF. 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. [PMC free article] [PubMed]
  • Begun DJ, Aquadro CF. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. [PubMed]
  • Berry AJ, Ajioka JW, Kreitman M. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics. 1991 Dec;129(4):1111–1117. [PMC free article] [PubMed]
  • Charlesworth B. Mutation-selection balance and the evolutionary advantage of sex and recombination. Genet Res. 1990 Jun;55(3):199–221. [PubMed]
  • Charlesworth B. Evolutionary biology. New genes sweep clean. Nature. 1992 Apr 9;356(6369):475–476. [PubMed]
  • 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. [PubMed]
  • Charlesworth D, Morgan MT, Charlesworth B. The effect of linkage and population size on inbreeding depression due to mutational load. Genet Res. 1992 Feb;59(1):49–61. [PubMed]
  • Eanes WF, Labate J, Ajioka JW. Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster. Mol Biol Evol. 1989 Sep;6(5):492–502. [PubMed]
  • Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. [PMC free article] [PubMed]
  • Felsenstein J, Yokoyama S. The evolutionary advantage of recombination. II. Individual selection for recombination. Genetics. 1976 Aug;83(4):845–859. [PMC free article] [PubMed]
  • Haigh J. The accumulation of deleterious genes in a population--Muller's Ratchet. Theor Popul Biol. 1978 Oct;14(2):251–267. [PubMed]
  • Hedrick PW. Hitchhiking: a comparison of linkage and partial selfing. Genetics. 1980 Mar;94(3):791–808. [PMC free article] [PubMed]
  • Houle D, Hoffmaster DK, Assimacopoulos S, Charlesworth B. The genomic mutation rate for fitness in Drosophila. Nature. 1992 Sep 3;359(6390):58–60. [PubMed]
  • Kaplan NL, Hudson RR, Langley CH. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Kimura M. Theoretical foundation of population genetics at the molecular level. Theor Popul Biol. 1971 Jun;2(2):174–208. [PubMed]
  • Kimura M, Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. [PMC free article] [PubMed]
  • KIMURA M, MARUYAMA T, CROW JF. THE MUTATION LOAD IN SMALL POPULATIONS. Genetics. 1963 Oct;48:1303–1312. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Kondrashov AS. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. [PubMed]
  • Langley CH, 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. [PMC free article] [PubMed]
  • Martín-Campos JM, Comerón JM, 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. [PMC free article] [PubMed]
  • Maruyama T, Fuerst PA. Population bottlenecks and nonequilibrium models in population genetics. I. Allele numbers when populations evolve from zero variability. Genetics. 1984 Nov;108(3):745–763. [PMC free article] [PubMed]
  • Maruyama T, Fuerst PA. 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. [PMC free article] [PubMed]
  • McCracken GF, Selander RK. Self-fertilization and monogenic strains in natural populations of terrestrial slugs. Proc Natl Acad Sci U S A. 1980 Jan;77(1):684–688. [PMC free article] [PubMed]
  • Miyashita NT. Molecular and phenotypic variation of the Zw locus region in Drosophila melanogaster. Genetics. 1990 Jun;125(2):407–419. [PMC free article] [PubMed]
  • Mukai T, Chigusa SI, Mettler LE, Crow JF. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. [PMC free article] [PubMed]
  • Pollak E. On the theory of partially inbreeding finite populations. I. Partial selfing. Genetics. 1987 Oct;117(2):353–360. [PMC free article] [PubMed]
  • Stephan W, Mitchell SJ. Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae. Genetics. 1992 Dec;132(4):1039–1045. [PMC free article] [PubMed]
  • Sved JA. Heterosis at the level of the chromosome and at the level of the gene. Theor Popul Biol. 1972 Dec;3(4):491–506. [PubMed]
  • Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. [PMC free article] [PubMed]
  • Tajima F. The effect of change in population size on DNA polymorphism. Genetics. 1989 Nov;123(3):597–601. [PMC free article] [PubMed]
  • Thomson G. The effect of a selected locus on linked neutral loci. Genetics. 1977 Apr;85(4):753–788. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...