Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1994 Aug;137(4):1049–1056. doi: 10.1093/genetics/137.4.1049

The Effects of Mutation and Natural Selection on Codon Bias in the Genes of Drosophila

R M Kliman 1, J Hey 1
PMCID: PMC1206052  PMID: 7982559

Abstract

Codon bias varies widely among the loci of Drosophila melanogaster, and some of this diversity has been explained by variation in the strength of natural selection. A study of correlations between intron and coding region base composition shows that variation in mutation pattern also contributes to codon bias variation. This finding is corroborated by an analysis of variance (ANOVA), which shows a tendency for introns from the same gene to be similar in base composition. The strength of base composition correlations between introns and codon third positions is greater for genes with low codon bias than for genes with high codon bias. This pattern can be explained by an overwhelming effect of natural selection, relative to mutation, in highly biased loci. In particular, this correlation is absent when examining fourfold degenerate sites of highly biased genes. In general, it appears that selection acts more strongly in choosing among fourfold degenerate codons than among twofold degenerate codons. Although the results indicate regional variation in mutational bias, no evidence is found for large scale regions of compositional homogeneity.

Full Text

The Full Text of this article is available as a PDF (870.7 KB).

Selected References

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

  1. Bennetzen J. L., Hall B. D. Codon selection in yeast. J Biol Chem. 1982 Mar 25;257(6):3026–3031. [PubMed] [Google Scholar]
  2. Bernardi G., Bernardi G. Codon usage and genome composition. J Mol Evol. 1985;22(4):363–365. doi: 10.1007/BF02115693. [DOI] [PubMed] [Google Scholar]
  3. Bernardi G., Olofsson B., Filipski J., Zerial M., Salinas J., Cuny G., Meunier-Rotival M., Rodier F. The mosaic genome of warm-blooded vertebrates. Science. 1985 May 24;228(4702):953–958. doi: 10.1126/science.4001930. [DOI] [PubMed] [Google Scholar]
  4. Bernardi G. The isochore organization of the human genome. Annu Rev Genet. 1989;23:637–661. doi: 10.1146/annurev.ge.23.120189.003225. [DOI] [PubMed] [Google Scholar]
  5. Brunk B. P., Adler P. N. The sequence of the Drosophila regulatory gene Suppressor two of zeste. Nucleic Acids Res. 1991 Jun 11;19(11):3149–3149. doi: 10.1093/nar/19.11.3149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carulli J. P., Krane D. E., Hartl D. L., Ochman H. Compositional heterogeneity and patterns of molecular evolution in the Drosophila genome. Genetics. 1993 Jul;134(3):837–845. doi: 10.1093/genetics/134.3.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Charlesworth B., Morgan M. T., Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. doi: 10.1093/genetics/134.4.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eyre-Walker A. Recombination and mammalian genome evolution. Proc Biol Sci. 1993 Jun 22;252(1335):237–243. doi: 10.1098/rspb.1993.0071. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gouy M., Gautier C. Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res. 1982 Nov 25;10(22):7055–7074. doi: 10.1093/nar/10.22.7055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guthrie C. Messenger RNA splicing in yeast: clues to why the spliceosome is a ribonucleoprotein. Science. 1991 Jul 12;253(5016):157–163. doi: 10.1126/science.1853200. [DOI] [PubMed] [Google Scholar]
  12. Hill W. G., Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed] [Google Scholar]
  13. Holmquist G. P. Evolution of chromosome bands: molecular ecology of noncoding DNA. J Mol Evol. 1989 Jun;28(6):469–486. doi: 10.1007/BF02602928. [DOI] [PubMed] [Google Scholar]
  14. Holmquist G. P. Role of replication time in the control of tissue-specific gene expression. Am J Hum Genet. 1987 Feb;40(2):151–173. [PMC free article] [PubMed] [Google Scholar]
  15. Hooper J. E., Scott M. P. The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell. 1989 Nov 17;59(4):751–765. doi: 10.1016/0092-8674(89)90021-4. [DOI] [PubMed] [Google Scholar]
  16. Ikemura T. Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol. 1985 Jan;2(1):13–34. doi: 10.1093/oxfordjournals.molbev.a040335. [DOI] [PubMed] [Google Scholar]
  17. Mantel N. The detection of disease clustering and a generalized regression approach. Cancer Res. 1967 Feb;27(2):209–220. [PubMed] [Google Scholar]
  18. Montell C., Rubin G. M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron. 1989 Apr;2(4):1313–1323. doi: 10.1016/0896-6273(89)90069-x. [DOI] [PubMed] [Google Scholar]
  19. Moriyama E. N., Gojobori T. Rates of synonymous substitution and base composition of nuclear genes in Drosophila. Genetics. 1992 Apr;130(4):855–864. doi: 10.1093/genetics/130.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moriyama E. N., Hartl D. L. Codon usage bias and base composition of nuclear genes in Drosophila. Genetics. 1993 Jul;134(3):847–858. doi: 10.1093/genetics/134.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schaeffer S. W., Miller E. L. Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura. Genetics. 1993 Oct;135(2):541–552. doi: 10.1093/genetics/135.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharp P. M., Devine K. M. 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. doi: 10.1093/nar/17.13.5029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sharp P. M., Li W. H. An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol. 1986;24(1-2):28–38. doi: 10.1007/BF02099948. [DOI] [PubMed] [Google Scholar]
  24. Sharp P. M., Li W. H. The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Mol Biol Evol. 1987 May;4(3):222–230. doi: 10.1093/oxfordjournals.molbev.a040443. [DOI] [PubMed] [Google Scholar]
  25. Shields D. C., Sharp P. M., Higgins D. G., 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. doi: 10.1093/oxfordjournals.molbev.a040525. [DOI] [PubMed] [Google Scholar]
  26. Shields D. C., Sharp P. M. Synonymous codon usage in Bacillus subtilis reflects both translational selection and mutational biases. Nucleic Acids Res. 1987 Oct 12;15(19):8023–8040. doi: 10.1093/nar/15.19.8023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steinemann M. Chromosomal replication in Drosophila virilis. III. Organization of active origins in the highly polytene salivary gland cells. Chromosoma. 1981;82(2):289–307. doi: 10.1007/BF00286112. [DOI] [PubMed] [Google Scholar]
  28. Wolfe K. H. Mammalian DNA replication: mutation biases and the mutation rate. J Theor Biol. 1991 Apr 21;149(4):441–451. doi: 10.1016/s0022-5193(05)80092-x. [DOI] [PubMed] [Google Scholar]
  29. Wolfe K. H., Sharp P. M., Li W. H. Mutation rates differ among regions of the mammalian genome. Nature. 1989 Jan 19;337(6204):283–285. doi: 10.1038/337283a0. [DOI] [PubMed] [Google Scholar]
  30. Wright F. The 'effective number of codons' used in a gene. Gene. 1990 Mar 1;87(1):23–29. doi: 10.1016/0378-1119(90)90491-9. [DOI] [PubMed] [Google Scholar]
  31. von Kalm L., Weaver J., DeMarco J., MacIntyre R. J., Sullivan D. T. Structural characterization of the alpha-glycerol-3-phosphate dehydrogenase-encoding gene of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5020–5024. doi: 10.1073/pnas.86.13.5020. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES