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PMID: 19359587 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Coding-sequence determinants of gene expression in Escherichia coli.

Science (New York, N.Y.) ·Vol. 324 ·No. 5924 ·2009-04-10 ·Pages 255-8

Kudla G, Murray AW, Tollervey D, Plotkin JB

Abstract

Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein (GFP). When expressed in Escherichia coli, GFP protein levels varied 250-fold across the library. GFP messenger RNA (mRNA) levels, mRNA degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.

MeSH Terms
Amino Acid Substitution Base Composition Cloning, Molecular Codon Escherichia coli/genetics,growth & development,metabolism Gene Expression Gene Library Genes, Synthetic Green Fluorescent Proteins/genetics,metabolism Mutation Nucleic Acid Conformation Protein Biosynthesis RNA Stability RNA, Bacterial/chemistry,genetics,metabolism RNA, Messenger/chemistry,genetics,metabolism Spectrometry, Fluorescence
Chemicals
Codon RNA, Bacterial RNA, Messenger Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kudla Grzegorz
Department of Biology and Program in Applied Mathematics and Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Murray Andrew W
Tollervey David
Plotkin Joshua B
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1170160
Published
2009-04-10
Pages
255-8
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3902468
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BB/D019621/1 · United Kingdom
NIGMS NIH HHS · P50 GM068763 · United States
Biotechnology and Biological Sciences Research Council · BB/DO19621/1 · United Kingdom
Wellcome Trust · BB/DO19621/1 · United Kingdom
External Links
PubMed source DOI: 10.1126/science.1170160 PMC Full Text View journal details
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