scholarly journals Codon usage of highly expressed genes affects proteome-wide translation efficiency

2018 ◽  
Vol 115 (21) ◽  
pp. E4940-E4949 ◽  
Author(s):  
Idan Frumkin ◽  
Marc J. Lajoie ◽  
Christopher J. Gregg ◽  
Gil Hornung ◽  
George M. Church ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Protein Translation ◽  
Translation Efficiency ◽  
Synonymous Codons ◽  
Codon Composition ◽  
Theoretical Predictions ◽  
Highly Expressed Genes

Although the genetic code is redundant, synonymous codons for the same amino acid are not used with equal frequencies in genomes, a phenomenon termed “codon usage bias.” Previous studies have demonstrated that synonymous changes in a coding sequence can exert significantciseffects on the gene’s expression level. However, whether the codon composition of a gene can also affect the translation efficiency of other genes has not been thoroughly explored. To study how codon usage bias influences the cellular economy of translation, we massively converted abundant codons to their rare synonymous counterpart in several highly expressed genes inEscherichia coli. This perturbation reduces both the cellular fitness and the translation efficiency of genes that have high initiation rates and are naturally enriched with the manipulated codon, in agreement with theoretical predictions. Interestingly, we could alleviate the observed phenotypes by increasing the supply of the tRNA for the highly demanded codon, thus demonstrating that the codon usage of highly expressed genes was selected in evolution to maintain the efficiency of global protein translation.

Codon usage bias affects α-amylase mRNA level by altering RNA stability and cytosine methylation patterns in Escherichia coli

2020 ◽  
Vol 66 (9) ◽  
pp. 521-528
Author(s):  
Yanzi Xing ◽  
Ruiqing Gong ◽  
Yichun Xu ◽  
Kunshan Liu ◽  
Mian Zhou
Keyword(s):  
Escherichia Coli ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Cytosine Methylation ◽  
Codon Optimization ◽  
Mrna Level ◽  
Protein Translation ◽  
Transcriptional Level ◽  
Translation Efficiency

Codon usage bias exists in almost every organism and is reported to regulate protein translation efficiency and folding. Besides translation, the preliminary role of codon usage bias on gene transcription has also been revealed in some eukaryotes such as Neurospora crassa. In this study, we took as an example the α-amylase-coding gene (amyA) and examined the role of codon usage bias in regulating gene expression in the typical prokaryote Escherichia coli. We confirmed the higher translation efficiency on codon-optimized amyA RNAs and found that the RNA level itself was also affected by codon optimization. The decreased RNA level was caused at least in part by altered mRNA stability at the post-transcriptional level. Codon optimization also altered the number of cytosine methylation sites. Examination on dcm knockouts suggested that cytosine methylation may be a minor mechanism adopted by codon bias to regulate gene RNA levels. More studies are required to verify the global effect of codon usage and to reveal its detailed mechanism on transcription.

scholarly journals Codon usage bias creates a ramp of hydrogen bonding at the 5′-end in prokaryotic ORFeomes

2019 ◽  
Author(s):  
Juan C. Villada ◽  
Maria F. Duran ◽  
Patrick K. H. Lee
Keyword(s):  
Hydrogen Bonding ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Translation Efficiency ◽  
Molecular Processes ◽  
Molecular Feature ◽  
Web Based ◽  
Synonymous Codons ◽  
Double Stranded Dna ◽  
Codon Positions

Codon usage bias exerts control over a wide variety of molecular processes. The positioning of synonymous codons within coding sequences (CDSs) dictates protein expression by mechanisms such as local translation efficiency, mRNA Gibbs free energy, and protein co-translational folding. In this work, we explore how codon variants affect the position-dependent content of hydrogen bonding, which in turn influences energy requirements for unwinding double-stranded DNA. By analyzing over 14,000 bacterial, archaeal, and fungal ORFeomes, we found that Bacteria and Archaea exhibit an exponential ramp of hydrogen bonding at the 5′-end of CDSs, while a similar ramp was not found in Fungi. The ramp develops within the first 20 codon positions in prokaryotes, eventually reaching a steady carrying capacity of hydrogen bonding that does not differ from Fungi. Selection against uniformity tests proved that selection acts against synonymous codons with high content of hydrogen bonding at the 5′-end of prokaryotic ORFeomes. Overall, this study provides novel insights into the molecular feature of hydrogen bonding that is governed by the genetic code at the 5′-end of CDSs. A web-based application to analyze the position-dependent hydrogen bonding of ORFeomes has been developed and is publicly available (https://juanvillada.shinyapps.io/hbonds/).

scholarly journals Codon Usage Patterns inCorynebacterium glutamicum: Mutational Bias, Natural Selection and Amino Acid Conservation

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Guiming Liu ◽  
Jinyu Wu ◽  
Huanming Yang ◽  
Qiyu Bao
Keyword(s):  
Amino Acid ◽  
Codon Usage ◽  
Mutational Bias ◽  
Multivariate Statistical ◽  
Synonymous Codons ◽  
Usage Patterns ◽  
Highly Expressed Genes ◽  
Leading Strand ◽  
Synonymous And Nonsynonymous Substitutions ◽  
Amino Acid Conservation

The alternative synonymous codons inCorynebacterium glutamicum, a well-known bacterium used in industry for the production of amino acid, have been investigated by multivariate analysis. AsC. glutamicumis a GC-rich organism, G and C are expected to predominate at the third position of codons. Indeed, overall codon usage analyses have indicated that C and/or G ending codons are predominant in this organism. Through multivariate statistical analysis, apart from mutational selection, we identified three other trends of codon usage variation among the genes. Firstly, the majority of highly expressed genes are scattered towards the positive end of the first axis, whereas the majority of lowly expressed genes are clustered towards the other end of the first axis. Furthermore, the distinct difference in the two sets of genes was that the C ending codons are predominate in putatively highly expressed genes, suggesting that the C ending codons are translationally optimal in this organism. Secondly, the majority of the putatively highly expressed genes have a tendency to locate on the leading strand, which indicates that replicational and transciptional selection might be invoked. Thirdly, highly expressed genes are more conserved than lowly expressed genes by synonymous and nonsynonymous substitutions among orthologous genes fromthe genomes ofC. glutamicumandC. diphtheriae. We also analyzed other factors such as the length of genes and hydrophobicity that might influence codon usage and found their contributions to be weak.

scholarly journals Interplay between Position-Dependent Codon Usage Bias and Hydrogen Bonding at the 5ʹ End of ORFeomes

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Juan C. Villada ◽  
Maria F. Duran ◽  
Patrick K. H. Lee
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Protein Biosynthesis ◽  
Translation Efficiency ◽  
Content Type ◽  
Synonymous Codons ◽  
Double Stranded Dna

ABSTRACT Codon usage bias exerts control over a wide variety of molecular processes. The positioning of synonymous codons within coding sequences (CDSs) dictates protein expression by mechanisms such as local translation efficiency, mRNA Gibbs free energy, and protein cotranslational folding. In this work, we explore how codon usage affects the position-dependent content of hydrogen bonding, which in turn influences energy requirements for unwinding double-stranded DNA (dsDNA). We categorized codons according to their hydrogen bond content and found differential effects on hydrogen bonding encoded by codon variants. The specific positional disposition of codon variants within CDSs creates a ramp of hydrogen bonding at the 5ʹ end of the ORFeome in Escherichia coli. CDSs occupying the first position of operons are subjected to selective pressure that reduces their hydrogen bonding compared to internal CDSs, and highly transcribed CDSs demand a lower maximum capacity of hydrogen bonds per codon, suggesting that the energetic requirement for unwinding the dsDNA in highly transcribed CDSs has evolved to be minimized in E. coli. Subsequent analysis of over 14,000 ORFeomes showed a pervasive ramp of hydrogen bonding at the 5ʹ end in Bacteria and Archaea that positively correlates with the probability of mRNA secondary structure formation. Both the ramp and the correlation were not found in Fungi. The position-dependent hydrogen bonding might be part of the mechanism that contributes to the coordination between transcription and translation in Bacteria and Archaea. A Web-based application to analyze the position-dependent hydrogen bonding of ORFeomes has been developed and is publicly available (https://juanvillada.shinyapps.io/hbonds/). IMPORTANCE Redundancy of the genetic code creates a vast space of alternatives to encode a protein. Synonymous codons exert control over a variety of molecular and physiological processes of cells mainly through influencing protein biosynthesis. Recent findings have shown that synonymous codon choice affects transcription by controlling mRNA abundance, mRNA stability, transcription termination, and transcript biosynthesis cost. In this work, by analyzing thousands of Bacteria, Archaea, and Fungi genomes, we extend recent findings by showing that synonymous codon choice, corresponding to the number of hydrogen bonds in a codon, can also have an effect on the energetic requirements for unwinding double-stranded DNA in a position-dependent fashion. This report offers new perspectives on the mechanism behind the transcription-translation coordination and complements previous hypotheses on the resource allocation strategies used by Bacteria and Archaea to manage energy efficiency in gene expression.

How Optimized Is the Translational Machinery in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae?

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Xuhua Xia
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Salmonella Typhimurium ◽  
Codon Usage ◽  
Translational Efficiency ◽  
Square Root ◽  
Translational Machinery ◽  
Mutual Adaptation ◽  
Trna Species

Abstract The optimization of the translational machinery in cells requires the mutual adaptation of codon usage and tRNA concentration, and the adaptation of tRNA concentration to amino acid usage. Two predictions were derived based on a simple deterministic model of translation which assumes that elongation of the peptide chain is rate-limiting. The highest translational efficiency is achieved when the codon recognized by the most abundant tRNA reaches the maximum frequency. For each codon family, the tRNA concentration is optimally adapted to codon usage when the concentration of different tRNA species matches the square-root of the frequency of their corresponding synonymous codons. When tRNA concentration and codon usage are well adapted to each other, the optimal content of all tRNA species carrying the same amino acid should match the square-root of the frequency of the amino acid. These predictions are examined against empirical data from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae.

The effect of expression levels on codon usage inPlasmodium falciparum

Parasitology ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 245-251 ◽  
Author(s):  
L. PEIXOTO ◽  
V. FERNÁNDEZ ◽  
H. MUSTO
Keyword(s):  
Amino Acids ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Codon Usage ◽  
Complete Sequence ◽  
Expression Data ◽  
Expression Levels ◽  
Synonymous Codons ◽  
Translational Selection ◽  
Highly Expressed Genes

The usage of alternative synonymous codons in the completely sequenced, extremely A+T-rich parasitePlasmodium falciparumwas studied. Confirming previous studies obtained with less than 3% of the total genes recently described, we found that A- and U-ending triplets predominate but translational selection increases the frequency of a subset of codons in highly expressed genes. However, some new results come from the analysis of the complete sequence. First, there is more variation in GC3 than previously described; second, the effect of natural selection acting at the level of translation has been analysed with real expression data at 4 different stages and third, we found that highly expressed proteins increment the frequency of energetically less expensive amino acids. The implications of these results are discussed.

scholarly journals Analysis of computational codon usage models and their association with translationally slow codons

2020 ◽  
Author(s):  
Gabriel Wright ◽  
Anabel Rodriguez ◽  
Jun Li ◽  
Patricia L. Clark ◽  
Tijana Milenković ◽  
...  
Keyword(s):  
Codon Usage ◽  
Computational Models ◽  
Selective Pressure ◽  
Synonymous Codon ◽  
Ground Truth ◽  
Protein Translation ◽  
Weak Correlation ◽  
Experimental Conditions ◽  
Synonymous Codons ◽  
Genome Wide

AbstractImproved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively. Others use the CUB observed only in highly expressed genes, which should be under selective pressure to be translated efficiently (and whose CUB may therefore be more indicative of translation rates). No prior work has analyzed these models for their ability to predict translational slowdowns. Here, we evaluate five models for their association with slowly translated positions as denoted by two independent ribosome footprint (RFP) count experiments from S. cerevisiae, because RFP data is often considered as a “ground truth” for translation rates across mRNA sequences. We show that all five considered models strongly associate with the RFP data and therefore have potential for estimating translational slowdowns. However, we also show that there is a weak correlation between RFP counts for the same genes originating from independent experiments, even when their experimental conditions are similar. This raises concerns about the efficacy of using current RFP experimental data for estimating translation rates and highlights a potential advantage of using computational models to understand translation rates instead.

Comparative analysis of codon usage bias in Crenarchaea and Euryarchaea genome reveals differential preference of synonymous codons to encode highly expressed ribosomal and RNA polymerase proteins

2016 ◽  
Vol 95 (3) ◽  
pp. 537-549 ◽  
Author(s):  
VISHWA JYOTI BARUAH ◽  
SIDDHARTHA SANKAR SATAPATHY ◽  
BHESH RAJ POWDEL ◽  
ROCKTOTPAL KONWARH ◽  
ALAK KUMAR BURAGOHAIN ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Rna Polymerase ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codons

Codon usage and protein sequence pattern dependency in different organisms: A Bioinformatics approach

2015 ◽  
Vol 13 (02) ◽  
pp. 1550002
Author(s):  
Mohammad-Hadi Foroughmand-Araabi ◽  
Bahram Goliaei ◽  
Kasra Alishahi ◽  
Mehdi Sadeghi ◽  
Sama Goliaei
Keyword(s):  
Gene Regulation ◽  
Codon Usage ◽  
Protein Sequence ◽  
Multinomial Logistic Regression ◽  
Translation Efficiency ◽  
Translation Rate ◽  
Protein Levels ◽  
Synonymous Codons ◽  
First Time

Although it is known that synonymous codons are not chosen randomly, the role of the codon usage in gene regulation is not clearly understood, yet. Researchers have investigated the relation between the codon usage and various properties, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Recently, a universal codon usage based mechanism for gene regulation is proposed. We studied the role of protein sequence patterns on the codons usage by related genes. Considering a subsequence of a protein that matches to a pattern or motif, we showed that, parts of the genes, which are translated to this subsequence, use specific ratios of synonymous codons. Also, we built a multinomial logistic regression statistical model for codon usage, which considers the effect of patterns on codon usage. This model justifies the observed codon usage preference better than the classic organism dependent codon usage. Our results showed that the codon usage plays a role in controlling protein levels, for genes that participate in a specific biological function. This is the first time that this phenomenon is reported.

scholarly journals The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid

2019 ◽  
Vol 11 (9) ◽  
pp. 2439-2456 ◽  
Author(s):  
Lucía D’Andrea ◽  
Francisco-Javier Pérez-Rodríguez ◽  
Montserrat de Castellarnau ◽  
Susana Guix ◽  
Enric Ribes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Sequence Space ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Critical Role ◽  
Translation Efficiency ◽  
Rare Codons ◽  
Codon Composition ◽  
Cellular Genome

AbstractHepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype–phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype–phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff—not naturally occurring in HAV infection—involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.

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