Published online 24 September 2004
Nucleic Acids Research, Vol. 32 No. 17 © Oxford University Press 2004; all rights reserved
Solving the riddle of codon usage preferences: a test for translational selection
School of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK
* To whom correspondence should be addressed. Tel: +44 20 7631 6869; Fax: +44 20 7631 6803; Email: m.reis{at}mail.cryst.bbk.ac.uk
Received June 2, 2004; Revised and Accepted August 31, 2004
Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model.
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