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 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 Coding translational rates: the hidden genetic code

2016 ◽  
Author(s):  
Luis Diambra
Keyword(s):  
Gene Expression ◽  
Protein Folding ◽  
Statistical Analysis ◽  
Drug Transport ◽  
Heterologous Gene Expression ◽  
Significant Preference ◽  
Coding Sequences ◽  
E Coli ◽  
Small Change ◽  
Translational Speed

ABSTRACTIn this paper we propose that translational rate is modulated by pairs of consecutive codons or bicodons. By a statistical analysis of coding sequences, associated with low or with high abundant proteins, we found some bicodons with significant preference usage for either of these sets. These usage preferences cannot be explained by the frequency usage of the single codons. We compute a pause propensity measure of all bicodons in nine organisms, which reveals that in many cases bicodon preference is shared between related organisms. We found that bicodons associated with sequences encoding low abundant proteins are involved in translational attenuation reported in SufIprotein in E. coli. Furthermore, we observe that the 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 the codon usage. These findings suggest that bicodon usage can be a more powerful framework to understand translational speed, protein folding efficiency, and to improve protocols to optimize heterologous gene expression.

scholarly journals Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 734
Author(s):  
Xuhua Xia
Keyword(s):  
Codon Usage ◽  
Translation Initiation ◽  
Mrna Stability ◽  
Stop Codon ◽  
Translation Termination ◽  
Critical Evaluation ◽  
Immunization Programs ◽  
Translation Elongation ◽  
Different Types ◽  
Similarities And Differences

The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5’-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5’-UTR and the downstream 3’-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine () complicates some of these optimization processes because is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.

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 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 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.

scholarly journals Multi-protein bridging factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jiyu Wang ◽  
Jie Zhou ◽  
Qidi Yang ◽  
Elizabeth J Grayhack
Keyword(s):  
Ribosomal Proteins ◽  
Entry Site ◽  
Yeast Saccharomyces Cerevisiae ◽  
Translation Elongation ◽  
Reading Frame ◽  
Archaeal Protein ◽  
Specific Proteins ◽  
A Site ◽  
Codon Pairs ◽  
Control Complex

Reading frame maintenance is critical for accurate translation. We show that the conserved eukaryotic/archaeal protein Mbf1 acts with ribosomal proteins Rps3/uS3 and eukaryotic Asc1/RACK1 to prevent frameshifting at inhibitory CGA-CGA codon pairs in the yeast Saccharomyces cerevisiae. Mutations in RPS3 that allow frameshifting implicate eukaryotic conserved residues near the mRNA entry site. Mbf1 and Rps3 cooperate to maintain the reading frame of stalled ribosomes, while Asc1 also mediates distinct events that result in recruitment of the ribosome quality control complex and mRNA decay. Frameshifting occurs through a +1 shift with a CGA codon in the P site and involves competition between codons entering the A site, implying that the wobble interaction of the P site codon destabilizes translation elongation. Thus, eukaryotes have evolved unique mechanisms involving both a universally conserved ribosome component and two eukaryotic-specific proteins to maintain the reading frame at ribosome stalls.

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
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