Efficient translation initiation dictates codon usage at gene start

Molecular Systems Biology

Kajetan Bentele¹  Paul Saffert²  Robert Rauscher²  Zoya Ignatova² 

[1] Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany;Insitute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany

关键词: codon usage;    mRNA structure;    translation;   

DOI  :  10.1038/msb.2013.32

来源: Wiley

【 摘 要 】

Abstract

The genetic code is degenerate; thus, protein evolution does not uniquely determine the coding sequence. One of the puzzles in evolutionary genetics is therefore to uncover evolutionary driving forces that result in specific codon choice. In many bacteria, the first 5–10 codons of protein-coding genes are often codons that are less frequently used in the rest of the genome, an effect that has been argued to arise from selection for slowed early elongation to reduce ribosome traffic jams. However, genome analysis across many species has demonstrated that the region shows reduced mRNA folding consistent with pressure for efficient translation initiation. This raises the possibility that unusual codon usage is a side effect of selection for reduced mRNA structure. Here we discriminate between these two competing hypotheses, and show that in bacteria selection favours codons that reduce mRNA folding around the translation start, regardless of whether these codons are frequent or rare. Experiments confirm that primarily mRNA structure, and not codon usage, at the beginning of genes determines the translation rate.

Synopsis

Rare codons are enriched at gene start in many genomes. Genome analysis and experimental testing show that this enrichment evolved to keep the ribosome binding site free from stable mRNA structures, in order to facilitate efficient translation initiation.

• The use of rare codons coincides with suppression of mRNA structures at the ribosome binding site across genomes.
• There is preferential selection for synonymous codons that reduce GC-content at the beginning of genes and a stronger pressure for rare codon usage in GC-rich organisms.
• Amino acids encoded by AU-rich codons are preferred at gene start.
• Experimental results show that mRNA structure at translation start strongly influences protein yield.

【 授权许可】

CC BY-NC-SA   
Copyright © 2013 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.