CODON PAIR UTILIZATION BIASES INFLUENCE TRANSLATIONAL ELONGATION STEPTIMES

Two independent assays capable of measuring the relative in vivo trans lational step times across a selected codon pair in a growing polypept ide in the bacterium Escherichia coli have been employed to demonstrat e that codon pairs observed in protein coding sequences more frequentl y than predicted (over-represented codon pairs) are translated slower than pairs observed less frequently than expected (under-represented c odon pairs). These results are consistent with the findings that trans lational step times are influenced by codon context and that these con text effects are related to the compatabilities of adjacent tRNA isoac ceptor molecules on the surface of a translating ribosome. These resul ts also support our previous suggestion that the frequency of one codo n next to another has co-evolved with the structure and abundance of t RNA isoacceptors in order to control the rates of translational step t imes without imposing additional constraints on amino acid sequences o r protein structures.