Efficient translation initiation dictates codon usage at gene start

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‐c...

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Main Authors: Kajetan Bentele, Paul Saffert, Robert Rauscher, Zoya Ignatova, Nils Blüthgen
Format: Article
Language:English
Published: Springer Nature 2013-06-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2013.32
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author Kajetan Bentele
Paul Saffert
Robert Rauscher
Zoya Ignatova
Nils Blüthgen
author_facet Kajetan Bentele
Paul Saffert
Robert Rauscher
Zoya Ignatova
Nils Blüthgen
author_sort Kajetan Bentele
collection DOAJ
description 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.
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publisher Springer Nature
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spelling doaj-art-9e69abfa1da34d9080667dcd9cbaca602025-08-20T03:06:30ZengSpringer NatureMolecular Systems Biology1744-42922013-06-019111010.1038/msb.2013.32Efficient translation initiation dictates codon usage at gene startKajetan Bentele0Paul Saffert1Robert Rauscher2Zoya Ignatova3Nils Blüthgen4Institute for Theoretical Biology, Humboldt Universität zu BerlinInsitute of Biochemistry and Biology, University of PotsdamInsitute of Biochemistry and Biology, University of PotsdamInsitute of Biochemistry and Biology, University of PotsdamInstitute for Theoretical Biology, Humboldt Universität zu BerlinAbstract 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.https://doi.org/10.1038/msb.2013.32codon usagemRNA structuretranslation
spellingShingle Kajetan Bentele
Paul Saffert
Robert Rauscher
Zoya Ignatova
Nils Blüthgen
Efficient translation initiation dictates codon usage at gene start
Molecular Systems Biology
codon usage
mRNA structure
translation
title Efficient translation initiation dictates codon usage at gene start
title_full Efficient translation initiation dictates codon usage at gene start
title_fullStr Efficient translation initiation dictates codon usage at gene start
title_full_unstemmed Efficient translation initiation dictates codon usage at gene start
title_short Efficient translation initiation dictates codon usage at gene start
title_sort efficient translation initiation dictates codon usage at gene start
topic codon usage
mRNA structure
translation
url https://doi.org/10.1038/msb.2013.32
work_keys_str_mv AT kajetanbentele efficienttranslationinitiationdictatescodonusageatgenestart
AT paulsaffert efficienttranslationinitiationdictatescodonusageatgenestart
AT robertrauscher efficienttranslationinitiationdictatescodonusageatgenestart
AT zoyaignatova efficienttranslationinitiationdictatescodonusageatgenestart
AT nilsbluthgen efficienttranslationinitiationdictatescodonusageatgenestart