CODON PAIRS, CODON CONTEXT AND TRANSLATIONAL EFFICIENCY

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Codon pair utilization patterns in Escherichia coli, yeast, mouse, rat and human (and presumably all organisms) are highly biased, above and beyond previously noted biases in protein coding sequences. This codon pair bias is independent of codon usage, amino acid pair bias or adjacent dinucleotide bias. Codon pair bias is limited to nearest neighbors and it is directional. It is possible that codon pair bias is the result of the biological consequences of interactions between adjacent tRNA molecules on the surface of a translating ribosome, and that the compatibilities of adjacent cognate tRNA influence the translational step-times across each codon pair. Indeed a survey of the literature reveals many reports that support these types of tRNA-tRNA interactions, and evidence is presented here that, in E coli, highly over-represented codon pairs are translated much more slowly than under-represented codon pairs. It is proposed that species-specific codon pair utilization patterns have evolved so that the kinetics of translation can be controlled without constraints on amino acid sequences, and that translational step-times are related, perhaps in a predictable manner, to the species-specific patterns of codon pair utilization. If this is the case, then an understanding of this relationship would be of great functional significance and practical importance. The goal of the research proposed here is to further examine the correlation between codon pair bias and translational efficiency, and to test the hypothesis that codon pair bias is the result of the biological consequences of interactions between tRNA molecules on the surface of a translating ribosome.