Codon Usage in Molecular Evolution


In protein synthesis, succeeding amino acids are indicated by a sequence of codons in the gene. A given amino acid may be represented by up to six codons, making a choice between synonymous codons possible; this permits the creation of an evolutionary pattern of codon usages.

Keywords: codon bias; %G+C; GC3S; intron; exon; mRNA; tRNA; mtDNA

Figure 1.

Degenerate structure of the genetic code. Codons are read vertically. Each of the four rows represents a different level of degeneracy (number of codons per amino acid). The 61 amino acid codons are grouped in 20 sets of 1–6 synonymous members. Each six‐membered set (sextet) is composed of a quartet and a duet. Thus the code includes eight quartets and 12 duets, the isoleucine trio and the single codons of methionine and tryptophan, plus the three terminators. With quartet codons, changing the third base cannot affect the amino acid coded.



Aota S 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.

Bulmer M (1991) The selection‐mutation drift theory of synonymous codon usage. Genetics 129: 897–907.

Chiapello H, Lisacek F, Caboche M and Henau A (1998) Codon usage and gene function are related in sequences of Arabidopsis thaliana. Gene 209: GC1–GC38.

Ellis J, Morrison DA and Kalina B (1995) Comparision of the patterns of codon usage and bias between Brugia, Echinococcus, Onchocera and Schistosoma species. Parasitology Research 81: 388–393.

Gouy M and Gautier C (1982) Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Research 10: 7055–7074.

Gouy M and Grantham R (1980) Polypeptide elongation and tRNA cycling in Escherichia coli: a dynamic approach. FEBS Letters 115: 151–155.

Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185: 862–864.

Grantham R (1980) Nucleic acid sequence similarities: ‘poly(A) tendency’. FEBS Letters 121: 193–199.

Grantham R, Gautier C, Gouy M, Jacobzone M and Mercier R (1981) Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Research 9: r43–r74.

Grantham R, Greenland T, Lounil S et al. (1985) Molecular evolution of viruses as seen by nucleic acid sequence study. Bulletin de L’Institut Pasteur 83: 95–148.

Grantham R, Perrin P and Mouchiroud D (1986) Patterns in codon usage of different kinds of species. Oxford Surveys in Evolutionary Biology 3: 48–81.

Gray MW, Burger G and Leng BF (1999) Mitochondrial evolution. Science 283: 1476–1481.

Gygi SP, Rochon Y, Franza BR and Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Molecular and Cellular Biology 19: 1720–1730.

Ikemura T (1985) Codon usage and tRNA content in unicellular and multicellular organisms. Molecular Biology and Evolution 2: 13–34.

Kliman RM and Eyre‐Walker A (1998) Patterns of base composition within the genes of Drosophila melanogaster. Journal of Molecular Evolution 46: 534–541.

McMurray CT (1999) DNA secondary structure: a common and causative factor for expansion in human disease. Proceedings of the National Academy of Sciences of the USA 96: 1823–1825.

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.

Petrov DA and Hartl DL (1999) Patterns of nucleotide substitution in Drosophila and mammalian genomes. Proceedings of the National Academy of Sciences of the USA 96: 1475–1479.

Pontier J (1970) Traitement des informations chez les êtres vivants: Systèmes à service par essais successifs. Bulletin of Mathematical Biophysics 32: 83–148.

Sharp PM and Li W‐H (1987) 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 (1989) On the rate of DNA sequence evolution in Drosophila. Journal of Molecular Evolution 28: 398–402.

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

Xia X (1998) How optimized is the translational machinery in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae? Genetics 149: 37–44.

Further Reading

Angellotti MC, Bhuiyan SB, Chen G and Wan XF (2007) CodonO: codon usage bias analysis within and across genomes. Nucleic Acids Research 35: W132–W136.

Marquez R, Smit S and Knight R (2005) Do universal codon‐usage patterns minimize the effects of mutation and translation error? Genome Biology 6: R91.

Plotkin JB, Dushoff J, Desai MM and Fraser HB (2006) Codon usage and selection on proteins. Journal of Molecular Evolution 63: 635–653.

dos Reis M, Savva R and Wernisch L (2004) Solving the riddle of codon usage preferences: a test for translational selection. Nucleic Acids Research 32: 5036–5044.

Semon M, Lobry JR and Duret L (2006) No evidence for tissue‐specific adaptation of synonymous codon usage in humans. Molecular Biology and Evolution 23: 523–529.

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

* Required Field

How to Cite close
Grantham, Richard L(Dec 2007) Codon Usage in Molecular Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001806.pub2]