Nucleic Acids Research Advance Access published online on September 22, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp792
Computational Biology |
Universal function-specificity of codon usage
1Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, Quebec, H9X3V9, 2McGill Centre for Bioinformatics, McGill University, Duff Medical Building, 3775 University Street, Montreal, Quebec, H3A2B4, Canada, 3Department of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544, USA and 4Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G1Y6, Canada
*To whom correspondence should be addressed. Tel: +1 514 398 7721; Fax: +1 514 398 7857; Email: reza.salavati{at}mcgill.ca
Received August 16, 2009. Revised September 2, 2009. Accepted September 8, 2009.
Synonymous codon usage has long been known as a factor that affects average expression level of proteins in fast-growing microorganisms, but neither its role in dynamic changes of expression in response to environmental changes nor selective factors shaping it in the genomes of higher eukaryotes have been fully understood. Here, we propose that codon usage is ubiquitously selected to synchronize the translation efficiency with the dynamic alteration of protein expression in response to environmental and physiological changes. Our analysis reveals that codon usage is universally correlated with gene function, suggesting its potential contribution to synchronized regulation of genes with similar functions. We directly show that coexpressed genes have similar synonymous codon usages within the genomes of human, yeast, Caenorhabditis elegans and Escherichia coli. We also demonstrate that perturbing the codon usage directly affects the level or even direction of changes in protein expression in response to environmental stimuli. Perturbing tRNA composition also has tangible phenotypic effects on the cell. By showing that codon usage is universally function-specific, our results expand, to almost all organisms, the notion that cells may need to dynamically alter their intracellular tRNA composition in order to adapt to their new environment or physiological role.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.