Codon Usage


Genetic codes have degeneracy; that is, most amino acids (18 out of 20 in the universal genetic code) are encoded by more than one codon. Codons encoding the same amino acid are called synonymous codons. In both prokaryotic and eukaryotic genes, the synonymous codons are not used with equal frequencies.

Keywords: synonymous codon; translational selection; mutation bias; tRNA abundance; gene expression

Figure 1.

Codon usage bias in different organisms. (a, e) Escherichia coli, (b, f) Saccharomyces cerevisiae, (c, g) Drosophila melanogaster and (d, h) Homo sapiens. Codon usage bias is measured by the ‘effective number of codons’ (Nc). ‘G+C%’ is the G+C content at third codon positions. The sources for the sequence data are given in Table . The average Nc for each organism is 47.3 for E. coli, 50.6 for S. cerevisiae, 49.2 for D. melanogaster and 48.7 for H. sapiens. Arrowheads indicate the average Nc for ribosomal protein genes (including predicted genes) with more than 100 codons. The number of ribosomal protein genes included (and the average Nc) for each organism is 39 (36.3) for E. coli, 102 (29.9) for S. cerevisiae and 94 (39.3) for D. melanogaster.



Akashi H (1995) Inferring weak selection from patterns of polymorphism and divergence at ‘silent’ sites in Drosophila DNA. Genetics 139: 1067–1076.

Aota S‐I and Ikemura T (1986) Diversity in G+C content at the third position of codons in vertebrate genes and its cause. Nucleic Acids Research 14: 6345–6355.

Comeron JM and Aguadé M (1998) An evaluation of measure of synonymous codon usage bias. Journal of Molecular Evolution 47: 268–274.

Ikemura T (1992) Correlation between codon usage and tRNA content in microorganisms. In: Hatfield DL, Lee BJ and Pirtle RM (eds.) Transfer RNA in Protein Synthesis, pp. 87–111. Boca Raton, FL: CRC Press

Moriyama EN and Powell JR (1997) Codon usage bias and tRNA abundance in Drosophila. Journal of Molecular Evolution 45: 514–523.

Moriyama EN and Powell JR (1998) Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic Acids Research 26: 3188–3193.

National Center for Biotechnology Information. [ftp://ncbi.nlm.] [].

Sharp PM and Li W‐H (1987a) The codon adaptation index – a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Research 15: 1281–1295.

Sharp PM and Li W‐H (1987b) The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Molecular Biology and Evolution 4: 222–230.

Shields DC, Sharp PM, Higgins DG and Wright F (1988) ‘Silent’ sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Molecular Biology and Evolution 5: 704–716.

Stenico M, Lloyd AT and Sharp PM (1994) Codon usage in Caenorhabdiits elegans: delineation of translational selection and mutational biases. Nucleic Acids Research 22: 2437–2446.

Wright F (1990) The ‘effective number of codons’ used in a gene. Gene 87: 23–29.

Further Reading

Akashi H (1994) Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. Genetics 136: 927–935.

Akashi H (2001) Gene expression and molecular evolution. Current Opinion in Genetics and Development 11: 660–666.

Eyre‐Walker A (1999) Evidence of selection on silent site base composition in mammals: potential implications for the evolution of isochores and junk DNA. Genetics 152: 675–683.

Powell JR and Moriyama EN (1997) Evolution of codon usage bias in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 94: 7784–7790.

Urrutia AO and Hurst LD (2001) Codon usage bias covaries with expression breadth and the rate of synonymous evolution in humans, but this is not evidence for selection. Genetics 159: 1191–1199.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Moriyama, Etsuko N(Jul 2006) Codon Usage. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005102]