Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons
Abstract
The Sec secretion pathway is found across all domains of life. A critical feature of Sec secreted proteins is the signal peptide, a short peptide with distinct physicochemical properties located at the N-terminus of the protein. Previous work indicates signal peptides are biased towards translationally inefficient codons, which is hypothesized to be an adaptation driven by selection to improve the efficacy and efficiency of the protein secretion mechanisms. We investigate codon usage in the signal peptides of E. coli using the Codon Adaptation Index (CAI), the tRNA Adaptation Index (tAI), and the ribosomal overhead cost formulation of the stochastic evolutionary model of protein production rates (ROC-SEMPPR). Comparisons between signal peptides and 5'-end of cytoplasmic proteins using CAI and tAI are consistent with a preference for inefficient codons in signal peptides. Simulations reveal these differences are due to amino acid usage and gene expression – we find these differences disappear when accounting for both factors. In contrast, ROC-SEMPPR, a mechanistic population genetics model capable of separating the effects of selection and mutation bias, shows codon usage bias (CUB) of the signal peptides is indistinguishable from the 5'-ends of cytoplasmic proteins. Additionally, we find CUB at the 5'-ends is weaker than latermore »
- Authors:
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1576682
- Alternate Identifier(s):
- OSTI ID: 1528733
- Grant/Contract Number:
- AC05-00OR22725; MCB-1120370; MCB-1546402
- Resource Type:
- Published Article
- Journal Name:
- Biochimica et Biophysica Acta. Biomembranes
- Additional Journal Information:
- Journal Name: Biochimica et Biophysica Acta. Biomembranes Journal Volume: 1860 Journal Issue: 12; Journal ID: ISSN 0005-2736
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Cope, Alexander L., Hettich, Robert L., and Gilchrist, Michael A. Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons. Netherlands: N. p., 2018.
Web. doi:10.1016/j.bbamem.2018.09.010.
Cope, Alexander L., Hettich, Robert L., & Gilchrist, Michael A. Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons. Netherlands. https://doi.org/10.1016/j.bbamem.2018.09.010
Cope, Alexander L., Hettich, Robert L., and Gilchrist, Michael A. Sat .
"Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons". Netherlands. https://doi.org/10.1016/j.bbamem.2018.09.010.
@article{osti_1576682,
title = {Quantifying codon usage in signal peptides: Gene expression and amino acid usage explain apparent selection for inefficient codons},
author = {Cope, Alexander L. and Hettich, Robert L. and Gilchrist, Michael A.},
abstractNote = {The Sec secretion pathway is found across all domains of life. A critical feature of Sec secreted proteins is the signal peptide, a short peptide with distinct physicochemical properties located at the N-terminus of the protein. Previous work indicates signal peptides are biased towards translationally inefficient codons, which is hypothesized to be an adaptation driven by selection to improve the efficacy and efficiency of the protein secretion mechanisms. We investigate codon usage in the signal peptides of E. coli using the Codon Adaptation Index (CAI), the tRNA Adaptation Index (tAI), and the ribosomal overhead cost formulation of the stochastic evolutionary model of protein production rates (ROC-SEMPPR). Comparisons between signal peptides and 5'-end of cytoplasmic proteins using CAI and tAI are consistent with a preference for inefficient codons in signal peptides. Simulations reveal these differences are due to amino acid usage and gene expression – we find these differences disappear when accounting for both factors. In contrast, ROC-SEMPPR, a mechanistic population genetics model capable of separating the effects of selection and mutation bias, shows codon usage bias (CUB) of the signal peptides is indistinguishable from the 5'-ends of cytoplasmic proteins. Additionally, we find CUB at the 5'-ends is weaker than later segments of the gene. Results illustrate the value in using models grounded in population genetics to interpret genetic data. We show failure to account for mutation bias and the effects of gene expression on the efficacy of selection against translation inefficiency can lead to a misinterpretation of codon usage patterns.},
doi = {10.1016/j.bbamem.2018.09.010},
journal = {Biochimica et Biophysica Acta. Biomembranes},
number = 12,
volume = 1860,
place = {Netherlands},
year = {Sat Dec 01 00:00:00 EST 2018},
month = {Sat Dec 01 00:00:00 EST 2018}
}
https://doi.org/10.1016/j.bbamem.2018.09.010
Web of Science
Works referenced in this record:
The effect of context on synonymous codon usage in genes with low codon usage bias
journal, January 1990
- Bulmer, Michael
- Nucleic Acids Research, Vol. 18, Issue 10
Synonymous codon bias is related to gene length in Escherichia coli: selection for translational accuracy?
journal, July 1996
- Eyre-Walker, A.
- Molecular Biology and Evolution, Vol. 13, Issue 6
Solving the riddle of codon usage preferences: a test for translational selection
journal, September 2004
- Reis, M. d.
- Nucleic Acids Research, Vol. 32, Issue 17
A model of protein translation including codon bias, nonsense errors, and ribosome recycling
journal, April 2006
- Gilchrist, Michael A.; Wagner, Andreas
- Journal of Theoretical Biology, Vol. 239, Issue 4
Protein export through the bacterial Sec pathway
journal, November 2016
- Tsirigotaki, Alexandra; De Geyter, Jozefien; Šoštaric´, Nikolina
- Nature Reviews Microbiology, Vol. 15, Issue 1
Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding
journal, December 2012
- Pechmann, Sebastian; Frydman, Judith
- Nature Structural & Molecular Biology, Vol. 20, Issue 2
Biased codon usage in signal peptides: a role in protein export
journal, April 2009
- Zalucki, Yaramah M.; Beacham, Ifor R.; Jennings, Michael P.
- Trends in Microbiology, Vol. 17, Issue 4
Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: A proposal for a synonymous codon choice that is optimal for the E. coli translational system
journal, September 1981
- Ikemura, Toshimichi
- Journal of Molecular Biology, Vol. 151, Issue 3
Whole genome analysis reveals a high incidence of non-optimal codons in secretory signal sequences of Escherichia coli
journal, September 2004
- Power, Peter M.; Jones, Robert A.; Beacham, Ifor R.
- Biochemical and Biophysical Research Communications, Vol. 322, Issue 3
The codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications
journal, January 1987
- Sharp, Paul M.; Li, Wen-Hsiung
- Nucleic Acids Research, Vol. 15, Issue 3, p. 1281-1295
Analysis of mutational alterations in the hydrophilic segment of the maltose-binding protein signal peptide.
journal, January 1989
- Puziss, J. W.; Fikes, J. D.; Bassford, P. J.
- Journal of Bacteriology, Vol. 171, Issue 5
An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation
journal, April 2010
- Tuller, Tamir; Carmi, Asaf; Vestsigian, Kalin
- Cell, Vol. 141, Issue 2
Rare codons in E. coli and S. typhimurium signal sequences
journal, September 1985
- Burns, Dennis M.; Beacham, Ifor R.
- FEBS Letters, Vol. 189, Issue 2
Role of positive charge on the amino-terminal region of the signal peptide in protein secretion across the membrane.
journal, June 1982
- Inouye, S.; Soberon, X.; Franceschini, T.
- Proceedings of the National Academy of Sciences, Vol. 79, Issue 11
Clarifying the Translational Pausing Landscape in Bacteria by Ribosome Profiling
journal, February 2016
- Mohammad, Fuad; Woolstenhulme, Christopher J.; Green, Rachel
- Cell Reports, Vol. 14, Issue 4
Roles for Synonymous Codon Usage in Protein Biogenesis
journal, June 2015
- Chaney, Julie L.; Clark, Patricia L.
- Annual Review of Biophysics, Vol. 44, Issue 1
SignalP 4.0: discriminating signal peptides from transmembrane regions
journal, September 2011
- Petersen, Thomas Nordahl; Brunak, Søren; von Heijne, Gunnar
- Nature Methods, Vol. 8, Issue 10
Coupling between codon usage, translation and protein export in Escherichia coli
journal, May 2011
- Zalucki, Yaramah M.; Beacham, Ifor R.; Jennings, Michael P.
- Biotechnology Journal, Vol. 6, Issue 6
Effect of codon-optimized E. coli signal peptides on recombinant Bacillus stearothermophilus maltogenic amylase periplasmic localization, yield and activity
journal, July 2014
- Samant, Shalaka; Gupta, Gunja; Karthikeyan, Subbulakshmi
- Journal of Industrial Microbiology & Biotechnology, Vol. 41, Issue 9
Effects of the complete removal of basic amino acid residues from the signal peptide on secretion of lipoprotein in Escherichia coli.
journal, June 1983
- Vlasuk, G. P.; Inouye, S.; Ito, H.
- Journal of Biological Chemistry, Vol. 258, Issue 11
Secretory signal sequence non-optimal codons are required for expression and export of β-lactamase
journal, February 2008
- Zalucki, Yaramah M.; Gittins, Karlee L.; Jennings, Michael P.
- Biochemical and Biophysical Research Communications, Vol. 366, Issue 1
Experimental confirmation of a key role for non-optimal codons in protein export
journal, March 2007
- Zalucki, Yaramah M.; Jennings, Michael P.
- Biochemical and Biophysical Research Communications, Vol. 355, Issue 1
Co-translational protein targeting catalyzed by the Escherichia coli signal recognition particle and its receptor
journal, August 1997
- Powers, T.
- The EMBO Journal, Vol. 16, Issue 16
Intragenic Spatial Patterns of Codon Usage Bias in Prokaryotic and Eukaryotic Genomes
journal, December 2004
- Qin, Hong; Wu, Wei Biao; Comeron, Josep M.
- Genetics, Vol. 168, Issue 4
Directed evolution of efficient secretion in the SRP-dependent export of TolB
journal, October 2011
- Zalucki, Yaramah M.; Shafer, William M.; Jennings, Michael P.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1808, Issue 10
Codon usage bias in 5′ terminal coding sequences reveals distinct enrichment of gene functions
journal, October 2017
- Liu, Huiling; Rahman, Siddiq Ur; Mao, Yuanhui
- Genomics, Vol. 109, Issue 5-6
Unexpected correlations between gene expression and codon usage bias from microarray data for the whole Escherichia coli K-12 genome
journal, December 2003
- dos Reis, M.
- Nucleic Acids Research, Vol. 31, Issue 23
The rapid evolution of signal peptides is mainly caused by relaxed selection on non-synonymous and synonymous sites
journal, May 2009
- Li, Yu-Dong; Xie, Zhong-Yu; Du, Yi-Ling
- Gene, Vol. 436, Issue 1-2
Signal sequence non-optimal codons are required for the correct folding of mature maltose binding protein
journal, June 2010
- Zalucki, Yaramah M.; Jones, Christopher E.; Ng, Preston S. K.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 6
Rate-Limiting Steps in Yeast Protein Translation
journal, June 2013
- Shah, Premal; Ding, Yang; Niemczyk, Malwina
- Cell, Vol. 153, Issue 7
Effective population size and patterns of molecular evolution and variation
journal, March 2009
- Charlesworth, Brian
- Nature Reviews Genetics, Vol. 10, Issue 3
Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane—Distinct translocases and mechanisms
journal, September 2008
- Natale, Paolo; Brüser, Thomas; Driessen, Arnold J. M.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1778, Issue 9
Speed Controls in Translating Secretory Proteins in Eukaryotes - an Evolutionary Perspective
journal, January 2014
- Mahlab, Shelly; Linial, Michal
- PLoS Computational Biology, Vol. 10, Issue 1
Estimating Gene Expression and Codon-Specific Translational Efficiencies, Mutation Biases, and Selection Coefficients from Genomic Data Alone ‡
journal, May 2015
- Gilchrist, Michael A.; Chen, Wei-Chen; Shah, Premal
- Genome Biology and Evolution, Vol. 7, Issue 6
The ASA Statement on p -Values: Context, Process, and Purpose
journal, April 2016
- Wasserstein, Ronald L.; Lazar, Nicole A.
- The American Statistician, Vol. 70, Issue 2
Positively charged lysine at the N-terminus of the signal peptide of the Escherichia coli alkaline phosphatase provides the secretion efficiency and is involved in the interaction with anionic phospholipids
journal, February 1997
- Nesmeyanova, Marina A.; Karamyshev, Andrew L.; Karamysheva, Zemphyra N.
- FEBS Letters, Vol. 403, Issue 2
Explaining complex codon usage patterns with selection for translational efficiency, mutation bias, and genetic drift
journal, June 2011
- Shah, P.; Gilchrist, M. A.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 25
Quantifying Position-Dependent Codon Usage Bias
journal, April 2014
- Hockenberry, Adam J.; Sirer, M. Irmak; Amaral, Luís A. Nunes
- Molecular Biology and Evolution, Vol. 31, Issue 7
Combining Models of Protein Translation and Population Genetics to Predict Protein Production Rates from Codon Usage Patterns
journal, August 2007
- Gilchrist, M. A.
- Molecular Biology and Evolution, Vol. 24, Issue 11
Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding
journal, September 2015
- Yu, Chien-Hung; Dang, Yunkun; Zhou, Zhipeng
- Molecular Cell, Vol. 59, Issue 5
Genetic drift, selection and the evolution of the mutation rate
journal, October 2016
- Lynch, Michael; Ackerman, Matthew S.; Gout, Jean-Francois
- Nature Reviews Genetics, Vol. 17, Issue 11
Estimating Selection on Synonymous Codon Usage from Noisy Experimental Data
journal, March 2013
- Wallace, Edward W. J.; Airoldi, Edoardo M.; Drummond, D. Allan
- Molecular Biology and Evolution, Vol. 30, Issue 6
Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo
journal, November 2014
- Pechmann, Sebastian; Chartron, Justin W.; Frydman, Judith
- Nature Structural & Molecular Biology, Vol. 21, Issue 12
Bacterial Secretion Systems: An Overview
journal, February 2016
- Green, Erin R.; Mecsas, Joan
- Microbiology Spectrum, Vol. 4, Issue 1