Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Feb 2002; 160(2): 595–608.
PMCID: PMC1461979

Interactions between natural selection, recombination and gene density in the genes of Drosophila.

Abstract

In Drosophila, as in many organisms, natural selection leads to high levels of codon bias in genes that are highly expressed. Thus codon bias is an indicator of the intensity of one kind of selection that is experienced by genes and can be used to assess the impact of other genomic factors on natural selection. Among 13,000 genes in the Drosophila genome, codon bias has a slight positive, and strongly significant, association with recombination--as expected if recombination allows natural selection to act more efficiently when multiple linked sites segregate functional variation. The same reasoning leads to the expectation that the efficiency of selection, and thus average codon bias, should decline with gene density. However, this prediction is not confirmed. Levels of codon bias and gene expression are highest for those genes in an intermediate range of gene density, a pattern that may be the result of a tradeoff between the advantages for gene expression of close gene spacing and disadvantages arising from regulatory conflicts among tightly packed genes. These factors appear to overlay the more subtle effect of linkage among selected sites that gives rise to the association between recombination rate and codon bias.

Full Text

The Full Text of this article is available as a PDF (215K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, et al. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. [PubMed]
  • Akashi H. Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. Genetics. 1994 Mar;136(3):927–935. [PMC free article] [PubMed]
  • Akashi H. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics. 1995 Feb;139(2):1067–1076. [PMC free article] [PubMed]
  • Akashi H. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics. 1996 Nov;144(3):1297–1307. [PMC free article] [PubMed]
  • Akashi H. Codon bias evolution in Drosophila. Population genetics of mutation-selection drift. Gene. 1997 Dec 31;205(1-2):269–278. [PubMed]
  • Begun DJ. The frequency distribution of nucleotide variation in Drosophila simulans. Mol Biol Evol. 2001 Jul;18(7):1343–1352. [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]
  • Bell AC, West AG, Felsenfeld G. Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science. 2001 Jan 19;291(5503):447–450. [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]
  • Bennetzen JL, Hall BD. Codon selection in yeast. J Biol Chem. 1982 Mar 25;257(6):3026–3031. [PubMed]
  • Carvalho AB, Clark AG. Intron size and natural selection. Nature. 1999 Sep 23;401(6751):344–344. [PubMed]
  • Charlesworth B, Morgan MT, Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. [PMC free article] [PubMed]
  • Marais G, Mouchiroud D, Duret L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5688–5692. [PMC free article] [PubMed]
  • Chavancy G, Chevallier A, Fournier A, Garel JP. Adaptation of iso-tRNA concentration to mRNA codon frequency in the eukaryote cell. Biochimie. 1979;61(1):71–78. [PubMed]
  • Cohen BA, Mitra RD, Hughes JD, Church GM. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat Genet. 2000 Oct;26(2):183–186. [PubMed]
  • McDonald JH, Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. [PubMed]
  • McVean GA, Charlesworth B. The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation. Genetics. 2000 Jun;155(2):929–944. [PMC free article] [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]
  • Munte A, Aguade M, Segarra C. Changes in the recombinational environment affect divergence in the yellow gene of Drosophila. Mol Biol Evol. 2001 Jun;18(6):1045–1056. [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]
  • Farkas G, Leibovitch BA, Elgin SC. Chromatin organization and transcriptional control of gene expression in Drosophila. Gene. 2000 Aug 8;253(2):117–136. [PubMed]
  • Rice WR, Chippindale AK. Sexual recombination and the power of natural selection. Science. 2001 Oct 19;294(5542):555–559. [PubMed]
  • Sharp PM, Devine KM. Codon usage and gene expression level in Dictyostelium discoideum: highly expressed genes do 'prefer' optimal codons. Nucleic Acids Res. 1989 Jul 11;17(13):5029–5039. [PMC free article] [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]
  • Gouy M, Gautier C. Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res. 1982 Nov 25;10(22):7055–7074. [PMC free article] [PubMed]
  • Sharp PM, Li WH. The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987 Feb 11;15(3):1281–1295. [PMC free article] [PubMed]
  • Hey J. Selfish genes, pleiotropy and the origin of recombination. Genetics. 1998 Aug;149(4):2089–2097. [PMC free article] [PubMed]
  • Sharp PM, Li WH. The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Mol Biol Evol. 1987 May;4(3):222–230. [PubMed]
  • Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed]
  • Sharp PM, Averof M, Lloyd AT, Matassi G, Peden JF. DNA sequence evolution: the sounds of silence. Philos Trans R Soc Lond B Biol Sci. 1995 Sep 29;349(1329):241–247. [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]
  • Ising G, Block K. A transposon as a cytogenetic marker in Drosophila melanogaster. Mol Gen Genet. 1984;196(1):6–16. [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]
  • Sun FL, Cuaycong MH, Craig CA, Wallrath LL, Locke J, Elgin SC. The fourth chromosome of Drosophila melanogaster: interspersed euchromatic and heterochromatic domains. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5340–5345. [PMC free article] [PubMed]
  • Kimura M. Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature. 1977 May 19;267(5608):275–276. [PubMed]
  • Whitfield LS, Lovell-Badge R, Goodfellow PN. Rapid sequence evolution of the mammalian sex-determining gene SRY. Nature. 1993 Aug 19;364(6439):713–715. [PubMed]
  • Wright F. The 'effective number of codons' used in a gene. Gene. 1990 Mar 1;87(1):23–29. [PubMed]
  • Kliman RM. Recent selection on synonymous codon usage in Drosophila. J Mol Evol. 1999 Sep;49(3):343–351. [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...