Vol. 12, Issue 6, 944-955, June 2002

LETTER
Shannon Information Theoretic Computation of Synonymous Codon Usage Biases in Coding Regions of Human and Mouse Genomes

Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

Exonic GC of human mRNA reference sequences (RefSeqs), as well as A, C, G, and T in codon position 3 are linearly correlated with genomic GC. These observations utilize information from the completed human genome sequence and a large, high-quality set of human and mouse coding sequences, and are in accord with similar determinations published by others. A Shannon Information Theoretic measure of bias in synonymous codon usage was developed. When applied to either human or mouse RefSeqs, this measure is nonlinearly correlated with genomic, exonic, and third codon position A, C, G, and T. Information values between orthologous mouse and human RefSeqs are linearly correlated: mouse = 0.092 + 0.55 human. Mouse genes were consistently placed in genomic regions whose GC content was closer to 50% than was the GC content of the human ortholog. Since the (nonlinear) information versus percent GC curve has a minimum at 50% GC and monotonically increases with increasing distance from 50% GC, this phenomenon directly results in the low slope of 0.55. This appears to be a manifestation of an evolutionary strategy for placement of genes in regions of the genome with a GC content that relates synonymous codon bias and protein folding.

[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: D. Church and D. Maglott.]