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Nucleic Acids Research 2006 34(3):1015-1027; doi:10.1093/nar/gkj488
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Published online 9 February 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

tRNA properties help shape codon pair preferences in open reading frames

J. Ross Buchan, Lorna S. Aucott1 and Ian Stansfield*

School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences Foresterhill, Aberdeen AB25 2ZD, UK 1Department of Public Health, School of Medicine, University of Aberdeen Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK

*To whom correspondence should be addressed. Tel: +44 1224 555806; Fax: +44 1224 555844; Email: i.stansfield{at}abdn.ac.uk

Received October 26, 2005. Revised December 16, 2005. Accepted January 18, 2006.

Translation elongation is an accurate and rapid process, dependent upon efficient juxtaposition of tRNAs in the ribosomal A- and P-sites. Here, we sought evidence of A- and P-site tRNA interaction by examining bias in codon pair choice within open reading frames from a range of genomes. Three distinct and marked effects were revealed once codon and dipeptide biases had been subtracted. First, in the majority of genomes, codon pair preference is primarily determined by a tetranucleotide combination of the third nucleotide of the P-site codon, and all 3 nt of the A-site codon. Second, pairs of rare codons are generally under-used in eukaryotes, but over-used in prokaryotes. Third, the analysis revealed a highly significant effect of tRNA-mediated selection on codon pairing in unicellular eukaryotes, Bacillus subtilis, and the gamma proteobacteria. This was evident because in these organisms, synonymous codons decoded in the A-site by the same tRNA exhibit significantly similar P-site pairing preferences. Codon pair preference is thus influenced by the identity of A-site tRNAs, in combination with the P-site codon third nucleotide. Multivariate analysis identified conserved nucleotide positions within A-site tRNA sequences that modulate codon pair preferences. Structural features that regulate tRNA geometry within the ribosome may govern genomic codon pair patterns, driving enhanced translational fidelity and/or rate.


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