Genetic code translation displays a linear trade-off between efficiency and accuracy of tRNA selection
Author Affiliations
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, 751 24 Uppsala, Sweden
Edited by Peter B. Moore, Yale University, New Haven, CT, and approved November 11, 2011 (received for review October 6, 2011)
Abstract
Rapid and accurate translation of the genetic code into protein is fundamental to life. Yet due to lack of a suitable assay, little is known about the accuracy-determining parameters and their correlation with translational speed. Here, we develop such an assay, based on Mg2+ concentration changes, to determine maximal accuracy limits for a complete set of single-mismatch codon–anticodon interactions. We found a simple, linear trade-off between efficiency of cognate codon reading and accuracy of tRNA selection. The maximal accuracy was highest for the second codon position and lowest for the third. The results rationalize the existence of proofreading in code reading and have implications for the understanding of tRNA modifications, as well as of translation error-modulating ribosomal mutations and antibiotics. Finally, the results bridge the gap between in vivo and in vitro translation and allow us to calibrate our test tube conditions to represent the environment inside the living cell.
fidelity, rate-accuracy trade-off, ribosome. protein synthesis, elongation
Footnotes
1To whom correspondence should be addressed. E-mail:ehrenberg@xray.bmc.uu.se.
Author contributions: M.J. and M.E. designed research; M.J. and J.Z. performed research; M.J., J.Z., and M.E. analyzed data; and M.J. and M.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information on-line at
Freely available online through the PNAS open access option.
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