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.

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 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.

scholarly journals A code within the genetic code: codon usage regulates co-translational protein folding

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yi Liu
Keyword(s):  
Protein Folding ◽  
Codon Usage ◽  
Genetic Code ◽  
Synonymous Codon ◽  
Protein Structures ◽  
Translation Efficiency ◽  
Intrinsically Disordered ◽  
Synonymous Codons ◽  
Eukaryotic Organisms ◽  
And Function

Abstract The genetic code is degenerate, and most amino acids are encoded by two to six synonymous codons. Codon usage bias, the preference for certain synonymous codons, is a universal feature of all genomes examined. Synonymous codon mutations were previously thought to be silent; however, a growing body evidence now shows that codon usage regulates protein structure and gene expression through effects on co-translational protein folding, translation efficiency and accuracy, mRNA stability, and transcription. Codon usage regulates the speed of translation elongation, resulting in non-uniform ribosome decoding rates on mRNAs during translation that is adapted to co-translational protein folding process. Biochemical and genetic evidence demonstrate that codon usage plays an important role in regulating protein folding and function in both prokaryotic and eukaryotic organisms. Certain protein structural types are more sensitive than others to the effects of codon usage on protein folding, and predicted intrinsically disordered domains are more prone to misfolding caused by codon usage changes than other domain types. Bioinformatic analyses revealed that gene codon usage correlates with different protein structures in diverse organisms, indicating the existence of a codon usage code for co-translational protein folding. This review focuses on recent literature on the role and mechanism of codon usage in regulating translation kinetics and co-translational protein folding.

Characterization of Synonymous Codon Usage Bias in the UL1 Gene of Duck Plague Virus

2013 ◽  
Vol 641-642 ◽  
pp. 693-700
Author(s):  
Ling Jie Zuo ◽  
An Chun Cheng ◽  
Ming Shu Wang
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Expression System ◽  
Synonymous Codon Usage ◽  
E Coli ◽  
Synonymous Codons ◽  
Compositional Constraint ◽  
Main Factor

In this study, we calculated the codon usage bias in DPV CHv UL1 gene and performed a comparative analysis of synonymous codon patterns in UL1 of DPV CHv strain and other 19 reference herpesviruses. The results revealed that the synonymous codons with A and T at the third codon positon have widely usage in the codon of UL1 gene of DPV CHv. G + C compositional constraint was the main factor that determined the codon usage bias in UL1 gene. In addition, the codon usage bias of DPV CHv UL1 gene was compared with those of E. coli, yeast and human. There are 25 codons showing distinct usage differences between DPV and E. coli, 26 codons between DPV and yeast, and 21 codons between DPV and human. Therefore, the Human expression system is more suitable for heterologous expression of the DPV UL1 gene.

Characterization of Codon Usage Bias in the RA Ragb/SusD Gene

2013 ◽  
Vol 641-642 ◽  
pp. 654-665
Author(s):  
Si Si Yang ◽  
De Kang Zhu ◽  
Xiao Jia Wang ◽  
An Chun Cheng ◽  
Ming Shu Wang
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Target Genes ◽  
Synonymous Codon ◽  
Expression System ◽  
Synonymous Codon Usage ◽  
Effective Number ◽  
E Coli ◽  
Synonymous Codons ◽  
Effective Number Of Codons

The analysis on codon usage bias of Riemerella anatipestifer (RA) RagB/SusD gene (GenBank accession No. NC_017045.1) may improve our understanding of the evolution and pathogenesis of RA and provide a basis for understanding the relevant mechanism for biased usage of synonymous codons and for selecting appropriate expression systems to improve the expression of target genes. In this study, the synonymous codon usage in the RagB/SusD gene of RA and 19 reference bacteroidetes have been investigated. The results showed that codon usage bias in the RagB/SusD gene was strong bias towards the synonymous codons with A and T at the third codon position. A high level of diversity in codon usage bias existed, and the effective number of codons used in a gene plot revealed that the genetic heterogeneity in RagB/SusD gene of bacteroidetes was constrained by the G + C content. The codon adaptation index (CAI), effective number of codons (ENC), and GC3S values indicated synonymous codon usage bias in the RagB/SusD gene of bacteroidetes, and this synonymous bias was correlated with host evolution. The phylogentic analysis suggested that RagB/SusD was evolutionarily closer to Ornithobacterium rhinotracheale and that there was no significant deviation in codon usage in different bacteroidetes. There are 25 codons showing distinct usage differences between RA RagB/SusD and E. coli, 30 between RA RagB/SusD and Homo sapiens, 26 codons between RA RagB/SusD and yeast. Therefore the yeast and E. coli expression system may be suitable for the expression of RA RagB/SusD gene if some codons could be optimized.

scholarly journals Analysis of Mutation Bias in Shaping Codon Usage Bias and Its Association with Gene Expression Across Species

10.29007/87r9 ◽  
2020 ◽  
Author(s):  
Zhixiu Lu ◽  
Michael Gilchrist ◽  
Scott Emrich
Keyword(s):  
Gene Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Mutation Bias ◽  
Protein Coding ◽  
E Coli ◽  
Synonymous Codons ◽  
Computation Efficiency

Codon usage bias has been known to reflect the expression level of a protein-coding gene under the evolutionary theory that selection favors certain synonymous codons. Although measuring the effect of selection in simple organisms such as yeast and E. coli has proven to be effective and accurate, codon-based methods perform less well in plants and humans. In this paper, we extend a prior method that incorporates another evolutionary factor, namely mutation bias and its effect on codon usage. Our results indicate that prediction of gene expression is significantly improved under our framework, and suggests that quantification of mutation bias is essential for fully understanding synonymous codon usage. We also propose an improved method, namely MLE-Φ, with much greater computation efficiency and a wider range of applications. An implementation of this method is provided at https://github.com/luzhixiu1996/MLE- Phi.

scholarly journals Codon usage bias and environmental adaptation in microbial organisms

2021 ◽  
Author(s):  
Davide Arella ◽  
Maddalena Dilucca ◽  
Andrea Giansanti
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Pathogenic Bacteria ◽  
Large Scale ◽  
Synonymous Codon ◽  
Principal Component ◽  
Gene Copy ◽  
Phenotypic Traits ◽  
Translational Efficiency ◽  
Microbial Organisms

AbstractIn each genome, synonymous codons are used with different frequencies; this general phenomenon is known as codon usage bias. It has been previously recognised that codon usage bias could affect the cellular fitness and might be associated with the ecology of microbial organisms. In this exploratory study, we investigated the relationship between codon usage bias, lifestyles (thermophiles vs. mesophiles; pathogenic vs. non-pathogenic; halophilic vs. non-halophilic; aerobic vs. anaerobic and facultative) and habitats (aquatic, terrestrial, host-associated, specialised, multiple) of 615 microbial organisms (544 bacteria and 71 archaea). Principal component analysis revealed that species with given phenotypic traits and living in similar environmental conditions have similar codon preferences, as represented by the relative synonymous codon usage (RSCU) index, and similar spectra of tRNA availability, as gauged by the tRNA gene copy number (tGCN). Moreover, by measuring the average tRNA adaptation index (tAI) for each genome, an index that can be associated with translational efficiency, we observed that organisms able to live in multiple habitats, including facultative organisms, mesophiles and pathogenic bacteria, are characterised by a reduced translational efficiency, consistently with their need to adapt to different environments. Our results show that synonymous codon choices might be under strong translational selection, which modulates the choice of the codons to differently match tRNA availability, depending on the organism’s lifestyle needs. To our knowledge, this is the first large-scale study that examines the role of codon bias and translational efficiency in the adaptation of microbial organisms to the environment in which they live.

Analysis of synonymous codon usage inShigella flexneri2a strain 301 and otherShigellaandEscherichia colistrains

2011 ◽  
Vol 57 (12) ◽  
pp. 1016-1023 ◽  
Author(s):  
Xue Lian Luo ◽  
Jian Guo Xu ◽  
Chang Yun Ye
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Shigella Flexneri ◽  
Synonymous Codon Usage ◽  
Codon Usage Pattern ◽  
Mutational Pressure ◽  
E Coli ◽  
Shigella Flexneri 2A ◽  
Usage Patterns

In this study, we analysed synonymous codon usage in Shigella flexneri 2a strain 301 (Sf301) and performed a comparative analysis of synonymous codon usage patterns in Sf301 and other strains of Shigella and Escherichia coli . Although there was a significant variety in codon usage bias among different Sf301 genes, there was a slight but observable codon usage bias that could primarily be attributable to mutational pressure and translational selection. In addition, the relative abundance of dinucleotides in Sf301 was observed to be independent of the overall base composition but was still caused by differential mutational pressure; this also shaped codon usage. By comparing the relative synonymous codon usage values across different Shigella and E. coli strains, we suggested that the synonymous codon usage pattern in the Shigella genomes was strain specific. This study represents a comprehensive analysis of Shigella codon usage patterns and provides a basic understanding of the mechanisms underlying codon usage bias.

scholarly journals Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

2014 ◽  
Vol 13 (3) ◽  
pp. 7347-7355 ◽  
Author(s):  
X.X. Ma ◽  
Y.P. Feng ◽  
J.L. Liu ◽  
L. Chen ◽  
Y.Q. Zhao ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
West Nile ◽  
In The Beginning ◽  
Synonymous Codon Usage Bias
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