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The role of codon selection in regulation of translation efficiency deduced from synthetic libraries

Sivan Navon and Yitzhak Pilpel*

Author Affiliations

Department of Molecular Genetics, Weizmann Institute of Science, PO Box 26, Rehovot, 76100, Israel

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Genome Biology 2011, 12:R12  doi:10.1186/gb-2011-12-2-r12

Published: 1 February 2011

Abstract

Background

Translation efficiency is affected by a diversity of parameters, including secondary structure of the transcript and its codon usage. Here we examine the effects of codon usage on translation efficiency by re-analysis of previously constructed synthetic expression libraries in Escherichia coli.

Results

We define the region in a gene that takes the longest time to translate as the bottleneck. We found that localization of the bottleneck at the beginning of a transcript promoted a high level of expression, especially if the computed dwell time of the ribosome within this region was sufficiently long. The location and translation time of the bottleneck were not correlated with the cost of expression, approximated by the fitness of the host cell, yet utilization of specific codons was. Particularly, enhanced usage of the codons UCA and CAU was correlated with increased cost of production, potentially due to sequestration of their corresponding rare tRNAs.

Conclusions

The distribution of codons along the genes appears to affect translation efficiency, consistent with analysis of natural genes. This study demonstrates how synthetic biology complements bioinformatics by providing a set-up for well controlled experiments in biology.