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. 1987 Feb 11;15(3):1281–1295. doi: 10.1093/nar/15.3.1281

The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications.

P M Sharp, W H Li
PMCID: PMC340524  PMID: 3547335

Abstract

A simple, effective measure of synonymous codon usage bias, the Codon Adaptation Index, is detailed. The index uses a reference set of highly expressed genes from a species to assess the relative merits of each codon, and a score for a gene is calculated from the frequency of use of all codons in that gene. The index assesses the extent to which selection has been effective in moulding the pattern of codon usage. In that respect it is useful for predicting the level of expression of a gene, for assessing the adaptation of viral genes to their hosts, and for making comparisons of codon usage in different organisms. The index may also give an approximate indication of the likely success of heterologous gene expression.

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Selected References

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  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., 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]
  3. Bonekamp F., Andersen H. D., Christensen T., Jensen K. F. Codon-defined ribosomal pausing in Escherichia coli detected by using the pyrE attenuator to probe the coupling between transcription and translation. Nucleic Acids Res. 1985 Jun 11;13(11):4113–4123. doi: 10.1093/nar/13.11.4113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burton Z. F., Gross C. A., Watanabe K. K., Burgess R. R. The operon that encodes the sigma subunit of RNA polymerase also encodes ribosomal protein S21 and DNA primase in E. coli K12. Cell. 1983 Feb;32(2):335–349. doi: 10.1016/0092-8674(83)90453-1. [DOI] [PubMed] [Google Scholar]
  5. Felmlee T., Pellett S., Welch R. A. Nucleotide sequence of an Escherichia coli chromosomal hemolysin. J Bacteriol. 1985 Jul;163(1):94–105. doi: 10.1128/jb.163.1.94-105.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foster D. L., Fillingame R. H. Stoichiometry of subunits in the H+-ATPase complex of Escherichia coli. J Biol Chem. 1982 Feb 25;257(4):2009–2015. [PubMed] [Google Scholar]
  7. 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]
  8. Grantham R., Gautier C., Gouy M., Jacobzone M., Mercier R. Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Res. 1981 Jan 10;9(1):r43–r74. doi: 10.1093/nar/9.1.213-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gribskov M., Devereux J., Burgess R. R. The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):539–549. doi: 10.1093/nar/12.1part2.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holm L. Codon usage and gene expression. Nucleic Acids Res. 1986 Apr 11;14(7):3075–3087. doi: 10.1093/nar/14.7.3075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Ikemura T. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. J Mol Biol. 1981 Feb 15;146(1):1–21. doi: 10.1016/0022-2836(81)90363-6. [DOI] [PubMed] [Google Scholar]
  13. Ikemura T. Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and Escherichia coli with reference to the abundance of isoaccepting transfer RNAs. J Mol Biol. 1982 Jul 15;158(4):573–597. doi: 10.1016/0022-2836(82)90250-9. [DOI] [PubMed] [Google Scholar]
  14. Li W. H., Gojobori T., Nei M. Pseudogenes as a paradigm of neutral evolution. Nature. 1981 Jul 16;292(5820):237–239. doi: 10.1038/292237a0. [DOI] [PubMed] [Google Scholar]
  15. McLachlan A. D., Staden R., Boswell D. R. A method for measuring the non-random bias of a codon usage table. Nucleic Acids Res. 1984 Dec 21;12(24):9567–9575. doi: 10.1093/nar/12.24.9567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miyata T., Hayashida H. Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5739–5743. doi: 10.1073/pnas.78.9.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ochman H., Selander R. K. Evidence for clonal population structure in Escherichia coli. Proc Natl Acad Sci U S A. 1984 Jan;81(1):198–201. doi: 10.1073/pnas.81.1.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pedersen S. Escherichia coli ribosomes translate in vivo with variable rate. EMBO J. 1984 Dec 1;3(12):2895–2898. doi: 10.1002/j.1460-2075.1984.tb02227.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Robinson M., Lilley R., Little S., Emtage J. S., Yarranton G., Stephens P., Millican A., Eaton M., Humphreys G. Codon usage can affect efficiency of translation of genes in Escherichia coli. Nucleic Acids Res. 1984 Sep 11;12(17):6663–6671. doi: 10.1093/nar/12.17.6663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sharp P. M. Does the 'non-coding' strand code? Nucleic Acids Res. 1985 Feb 25;13(4):1389–1397. doi: 10.1093/nar/13.4.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sharp P. M., Li W. H. Codon usage in regulatory genes in Escherichia coli does not reflect selection for 'rare' codons. Nucleic Acids Res. 1986 Oct 10;14(19):7737–7749. doi: 10.1093/nar/14.19.7737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharp P. M. Molecular evolution of bacteriophages: evidence of selection against the recognition sites of host restriction enzymes. Mol Biol Evol. 1986 Jan;3(1):75–83. doi: 10.1093/oxfordjournals.molbev.a040377. [DOI] [PubMed] [Google Scholar]
  23. Sharp P. M., Rogers M. S., McConnell D. J. Selection pressures on codon usage in the complete genome of bacteriophage T7. J Mol Evol. 1984;21(2):150–160. doi: 10.1007/BF02100089. [DOI] [PubMed] [Google Scholar]
  24. Sharp P. M., Tuohy T. M., Mosurski K. R. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res. 1986 Jul 11;14(13):5125–5143. doi: 10.1093/nar/14.13.5125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Toh H. T7 and E. coli share homology for replication-related gene products. FEBS Lett. 1986 Jan 6;194(2):245–248. doi: 10.1016/0014-5793(86)80093-x. [DOI] [PubMed] [Google Scholar]
  26. Varenne S., Buc J., Lloubes R., Lazdunski C. Translation is a non-uniform process. Effect of tRNA availability on the rate of elongation of nascent polypeptide chains. J Mol Biol. 1984 Dec 15;180(3):549–576. doi: 10.1016/0022-2836(84)90027-5. [DOI] [PubMed] [Google Scholar]
  27. Varenne S., Lazdunski C. Effect of distribution of unfavourable codons on the maximum rate of gene expression by an heterologous organism. J Theor Biol. 1986 May 7;120(1):99–110. doi: 10.1016/s0022-5193(86)80020-0. [DOI] [PubMed] [Google Scholar]

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