Degeneracy of the Genetic Code

The genetic code for translation of the gene sequence in protein biosynthesis is degenerate—there is more than one triplet codon for most amino acids. For example, tyrosine is encoded by UAU and UAC, and arginine is encoded by CGU, CGC, CGA, CGG, AGA, and AGG. Two codons that share the same first two nucleotides encode the same amino acid if the third nucleotide is either C or U, and they often do if the third nucleotide is A or G. Alternate synonymous codons are not used randomly. The GC content of the DNA, especially of bacteria, varies widely in different species, and there is a corresponding difference in codon usage. In bacteria and the yeast Saccharomyces cerevisiae, and even to some extent in Drosophila (except for the histone genes), the most frequently used codons are those that are decoded by abundant transfer RNA, and they are strongly preferred in genes expressed at high levels. In genes expressed at low levels, codon usage is more uniform (1-3.(  In bacteria with extreme DNA base composition biases (for example, the Mycoplasma capricolum genome is 25% G + C, whereas that of Micrococcus luteus is 74% G + C), not surprisingly, all genes have similar codon usage using those codons with the corresponding G + C content (4). Codon usage also varies among genes from the same genome. This is true of mammalian genomes but also, to some extent, in S. cerevisiae. Regions of differing G + C content were initially recognized in mammalian chromosomes and termed isochores. Overlying differences in codon usage between individual genes is the apparent higher density of genes in GC-rich isochores, and this may influence codon usage. As genome sequencing projects proceed, this relationship is expected to be clarified.

References

1. T. Ikemura (1981) J. Mol. Biol. 151, 389–409. 

2. M. Gouy and C. Gautier (1982) Nucl. Acids Res. 10, 7055–7074. 

3. H. Dong, L. Nilsson, and C. G. Kurland (1996) J. Mol. Biol. 260, 649–663.  4. T. Ohama, A. Muto, and S. Osawa (1990) Nucl. Acids Res. 18, 1565–1569.

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