scholarly journals A New Look at Codon Usage and Protein Expression

10.29007/d4tz ◽  
2019 ◽  
Author(s):  
Gabriel Wright ◽  
Anabel Rodriguez ◽  
Patricia Clark ◽  
Scott Emrich
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Empirical Data ◽  
Codon Usage Bias ◽  
Elongation Rate ◽  
Translation Rate ◽  
Translation Elongation ◽  
Promising Alternative ◽  
Highly Expressed Genes ◽  
Adaptation Index

%MinMax, a model of intra-gene translational elongation rate, relies on codon usage frequencies. Historically, %MinMax has used tables that measure codon usage bias for all genes in an organism, such as those found at HIVE-CUT. In this paper, we provide evidence that codon usage bias based on all genes is insufficient to accurately measure absolute translation rate. We show that alternative ”High-φ” codon usage tables, generated by another model (ROC-SEMPPR), are a promising alternative. By creating a hybrid model, future codon usage analyses and their applications (e.g., codon harmonization) are likely to more accurately measure the ”tempo” of translation elongation. We also suggest a High- φ alternative to the Codon Adaptation Index (CAI), a classic metric of codon usage bias based on highly expressed genes. Significantly, our new alternative is equally well correlated with empirical data as traditional CAI without using experimentally determined expression counts as input.

scholarly journals SARS-CoV-2 codon usage bias downregulates host expressed genes with similar codon usage

2020 ◽  
Author(s):  
Andres Mariano Alonso ◽  
Luis Diambra
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
World Health Organisation ◽  
Host Protein ◽  
World Health ◽  
Translation Rate ◽  
Proteomic Data ◽  
The World ◽  
Highly Expressed Genes ◽  
Infected Cells

ABSTRACTSevere acute respiratory syndrome is quickly spreading throughout the world and was declared as a pandemic by the World Health Organisation (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral proteins synthesis and its relationship with the proteins synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could conduct to an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes, and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis contributes to understand some deleterious collateral effect as result of the viral replication. In this manner, our finding contribute to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.

Protein Expression from Measles (MV) L Protein Genes Optimized and Suboptimized to Human and Canine Codon Usage Bias Varies with Construct and Cell Type

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Akash Shah ◽  
Elizabeth W. Uhl ◽  
Michelle L. Osborn ◽  
Frank Michel ◽  
Robert J. Hogan
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Cell Type ◽  
L Protein

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 Relative Codon Adaptation Index, a Sensitive Measure of Codon Usage Bias

2010 ◽  
Vol 6 ◽  
pp. EBO.S4608 ◽  
Author(s):  
Soohyun Lee ◽  
Seyeon Weon ◽  
Sooncheol Lee ◽  
Changwon Kang
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Codon Adaptation Index ◽  
Sensitive Measure ◽  
Adaptation Index

scholarly journals Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zhipeng Zhou ◽  
Yunkun Dang ◽  
Mian Zhou ◽  
Haiyan Yuan ◽  
Yi Liu
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Transcription Termination ◽  
Model Organism ◽  
Open Reading Frames ◽  
Strong Negative Correlation ◽  
Rare Codons ◽  
Cleavage And Polyadenylation ◽  
Mouse Cells

Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here, we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora, and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse cells. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression.

scholarly journals Differential bicodon usage in lowly and highly abundant proteins

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3081 ◽  
Author(s):  
Luis A. Diambra
Keyword(s):  
Codon Usage ◽  
Drug Transport ◽  
Heterologous Gene Expression ◽  
Elongation Rate ◽  
Translation Elongation ◽  
Synonymous Codons ◽  
Domains Of Life ◽  
Small Change ◽  
Protein Elongation ◽  
Codon Pairs

Degeneracy in the genetic code implies that different codons can encode the same amino acid. Usage preference of synonymous codons has been observed in all domains of life. There is much evidence suggesting that this bias has a major role on protein elongation rate, contributing to differential expression and to co-translational folding. In addition to codon usage bias, other preference variations have been observed such as codon pairs. In this paper, I report that codon pairs have significant different frequency usage for coding either lowly or highly abundant proteins. These usage preferences cannot be explained by the frequency usage of the single codons. The statistical analysis of coding sequences of nine organisms reveals that in many cases bicodon preferences are shared between related organisms. Furthermore, it is observed that misfolding in the drug-transport protein, encoded by MDR1 gene, is better explained by a big change in the pause propensity due to the synonymous bicodon variant, rather than by a relatively small change in codon usage. These findings suggest that codon pair usage can be a more powerful framework to understand translation elongation rate, protein folding efficiency, and to improve protocols to optimize heterologous gene expression.

scholarly journals Evolution of Codon Usage Bias in Henipaviruses Is Governed by Natural Selection and Is Host-Specific

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 604 ◽  
Author(s):  
Naveen Kumar ◽  
Diwakar Kulkarni ◽  
Benhur Lee ◽  
Rahul Kaushik ◽  
Sandeep Bhatia ◽  
...  
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Similarity Index ◽  
Hendra Virus ◽  
Human Beings ◽  
Mutation Pressure ◽  
Usage Patterns ◽  
Adaptation Index

Hendra virus (HeV) and Nipah virus (NiV) are among a group of emerging bat-borne paramyxoviruses that have crossed their species-barrier several times by infecting several hosts with a high fatality rate in human beings. Despite the fatal nature of their infection, a comprehensive study to explore their evolution and adaptation in different hosts is lacking. A study of codon usage patterns in henipaviruses may provide some fruitful insight into their evolutionary processes of synonymous codon usage and host-adapted evolution. Here, we performed a systematic evolutionary and codon usage bias analysis of henipaviruses. We found a low codon usage bias in the coding sequences of henipaviruses and that natural selection, mutation pressure, and nucleotide compositions shapes the codon usage patterns of henipaviruses, with natural selection being more important than the others. Also, henipaviruses showed the highest level of adaptation to bats of the genus Pteropus in the codon adaptation index (CAI), relative to the codon de-optimization index (RCDI), and similarity index (SiD) analyses. Furthermore, a comparison to recently identified henipa-like viruses indicated a high tRNA adaptation index of henipaviruses for human beings, mainly due to F, G and L proteins. Consequently, the study concedes the substantial emergence of henipaviruses in human beings, particularly when paired with frequent exposure to direct/indirect bat excretions.

scholarly journals Impact of translational selection on codon usage bias in the archaeon Methanococcus maripaludis

2010 ◽  
Vol 7 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Laura R. Emery ◽  
Paul M. Sharp
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Trna Genes ◽  
Strongly Correlated ◽  
Methanococcus Maripaludis ◽  
E Coli ◽  
Moderate Growth ◽  
Optimal Codons ◽  
Genome Wide ◽  
Highly Expressed Genes

Patterns of codon usage have been extensively studied among Bacteria and Eukaryotes, but there has been little investigation of species from the third domain of life, the Archaea. Here, we examine the nature of codon usage bias in a methanogenic archaeon, Methanococcus maripaludis . Genome-wide patterns of codon usage are dominated by a strong A + T bias, presumably largely reflecting mutation patterns. Nevertheless, there is variation among genes in the use of a subset of putatively translationally optimal codons, which is strongly correlated with gene expression level. In comparison with Bacteria such as Escherichia coli , the strength of selected codon usage bias in highly expressed genes in M. maripaludis seems surprisingly high given its moderate growth rate. However, the pattern of selected codon usage differs between M. maripaludis and E. coli : in the archaeon, strongly selected codon usage bias is largely restricted to twofold degenerate amino acids (AAs). Weaker bias among the codons for fourfold degenerate AAs is consistent with the small number of tRNA genes in the M. maripaludis genome.

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