• 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. Jun 2000; 155(2): 929–944.
PMCID: PMC1461092

The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation.

Abstract

Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting between weakly selected alleles, can restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synonymous-site mutations, considering the fate of novel variants in a two-locus model and the equilibrium effects of interference with multiple loci and reversible mutation. We find that weak selection Hill-Robertson (wsHR) interference can considerably reduce adaptation, e.g., codon bias, and, to a lesser extent, levels of polymorphism, particularly in regions of low recombination. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also generates specific patterns of linkage disequilibrium. While the selection coefficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may explain the unexpected constancy of codon bias across species of very different census population sizes, as well as several unusual features of codon usage in Drosophila.

Full Text

The Full Text of this article is available as a PDF (397K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hartl DL, Moriyama EN, Sawyer SA. Selection intensity for codon bias. Genetics. 1994 Sep;138(1):227–234. [PMC free article] [PubMed]
  • Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [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]
  • Kliman RM, Hey J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol. 1993 Nov;10(6):1239–1258. [PubMed]
  • Akashi H. Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics. 1999 Jan;151(1):221–238. [PMC free article] [PubMed]
  • Kondrashov AS. Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over? J Theor Biol. 1995 Aug 21;175(4):583–594. [PubMed]
  • Akashi H, Schaeffer SW. Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. Genetics. 1997 May;146(1):295–307. [PMC free article] [PubMed]
  • Krone SM, Neuhauser C. Ancestral Processes with Selection. Theor Popul Biol. 1997 Jun;51(3):210–237. [PubMed]
  • Ballard JW, Kreitman M. Unraveling selection in the mitochondrial genome of Drosophila. Genetics. 1994 Nov;138(3):757–772. [PMC free article] [PubMed]
  • Barton NH. Linkage and the limits to natural selection. Genetics. 1995 Jun;140(2):821–841. [PMC free article] [PubMed]
  • Bauer VL, Aquadro CF. Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1997 Dec;14(12):1252–1257. [PubMed]
  • Lynch M. Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes. Mol Biol Evol. 1997 Sep;14(9):914–925. [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]
  • Lynch M, Blanchard JL. Deleterious mutation accumulation in organelle genomes. Genetica. 1998;102-103(1-6):29–39. [PubMed]
  • Birky CW, Jr, Walsh JB. Effects of linkage on rates of molecular evolution. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6414–6418. [PMC free article] [PubMed]
  • Smith JM, Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed]
  • Braverman JM, Hudson RR, Kaplan NL, Langley CH, Stephan W. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. Genetics. 1995 Jun;140(2):783–796. [PMC free article] [PubMed]
  • Smith JM, Smith NH, O'Rourke M, Spratt BG. How clonal are bacteria? Proc Natl Acad Sci U S A. 1993 May 15;90(10):4384–4388. [PMC free article] [PubMed]
  • Bulmer M. The selection-mutation-drift theory of synonymous codon usage. Genetics. 1991 Nov;129(3):897–907. [PMC free article] [PubMed]
  • Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. [PubMed]
  • Moran NA. Accelerated evolution and Muller's rachet in endosymbiotic bacteria. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2873–2878. [PMC free article] [PubMed]
  • Moriyama EN, Powell JR. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. [PubMed]
  • Moriyama EN, Powell JR. Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic Acids Res. 1998 Jul 1;26(13):3188–3193. [PMC free article] [PubMed]
  • Charlesworth D, Charlesworth B, Morgan MT. The pattern of neutral molecular variation under the background selection model. Genetics. 1995 Dec;141(4):1619–1632. [PMC free article] [PubMed]
  • Chiapello H, Lisacek F, Caboche M, Hénaut A. Codon usage and gene function are related in sequences of Arabidopsis thaliana. Gene. 1998 Mar 16;209(1-2):GC1–GC38. [PubMed]
  • Nachman MW. Deleterious mutations in animal mitochondrial DNA. Genetica. 1998;102-103(1-6):61–69. [PubMed]
  • Comeron JM, Kreitman M, Aguadé M. Natural selection on synonymous sites is correlated with gene length and recombination in Drosophila. Genetics. 1999 Jan;151(1):239–249. [PMC free article] [PubMed]
  • Otto SP, Barton NH. The evolution of recombination: removing the limits to natural selection. Genetics. 1997 Oct;147(2):879–906. [PMC free article] [PubMed]
  • Duret L, Mouchiroud D. Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4482–4487. [PMC free article] [PubMed]
  • Powell JR, Moriyama EN. Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7784–7790. [PMC free article] [PubMed]
  • Eyre-Walker A, Bulmer M. Synonymous substitution rates in enterobacteria. Genetics. 1995 Aug;140(4):1407–1412. [PMC free article] [PubMed]
  • Price GR. Selection and covariance. Nature. 1970 Aug 1;227(5257):520–521. [PubMed]
  • Przeworski M, Charlesworth B, Wall JD. Genealogies and weak purifying selection. Mol Biol Evol. 1999 Feb;16(2):246–252. [PubMed]
  • Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. [PMC free article] [PubMed]
  • Santiago E, Caballero A. Effective size of populations under selection. Genetics. 1995 Feb;139(2):1013–1030. [PMC free article] [PubMed]
  • Santiago E, Caballero A. Effective size and polymorphism of linked neutral loci in populations under directional selection. Genetics. 1998 Aug;149(4):2105–2117. [PMC free article] [PubMed]
  • Sawyer SA, Hartl DL. Population genetics of polymorphism and divergence. Genetics. 1992 Dec;132(4):1161–1176. [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]
  • Sharp PM, Li WH. An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol. 1986;24(1-2):28–38. [PubMed]
  • Sharp PM, Tuohy TM, Mosurski KR. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res. 1986 Jul 11;14(13):5125–5143. [PMC free article] [PubMed]
  • Watterson GA. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. [PubMed]
  • Shields DC, Sharp PM, Higgins DG, Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. [PubMed]
  • Wright S. Evolution in Mendelian Populations. Genetics. 1931 Mar;16(2):97–159. [PMC free article] [PubMed]
  • Stenico M, Lloyd AT, Sharp PM. Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res. 1994 Jul 11;22(13):2437–2446. [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...