The Relationship of the Accuracy of Aminoacyl-tRNA Synthesis to That of Translation

Abstract

No real process can be carried out with complete precision. This would require an infinite free-energy difference between a desired reaction and another to be discriminated against. That is, some reactant other than the one desired can always utilize a given pathway at a finite rate, and/or an alternate pathway, and products exist even for an accurately selected reagent. This problem is particularly acute in biology because the evolution of one biochemical from another insures that a variety of structurally similar compounds will confront the cell. In spite of this unfavorable chemical similarity among substrates, large polymeric molecules must be constructed. During their synthesis and accumulation, every one of hundreds or thousands of synthetic steps are usually carried out correctly. Therefore, the accuracy of biosynthesis, e.g., the apparent production of a homogeneous protein, presents an immediate puzzle, and the study of this topic has become a subject in itself. Recent progress in understanding some contributions to the accuracy of translation makes this a good time to try a summary.

Most of what is known applies to the production of a protein with amino acid a rather than b (e.g., valine rather than isoleucine) at a given position in an otherwise accurately fashioned molecule. We discuss this type of error below, though there are other routes to substitution errors (e.g., incorrect binding of tRNAs on the ribosome), and errors of initiation and termination also occur and may be important.

WHAT IS THE OVERALL ERROR RATE OF TRANSLATION?
At the moment, data...