scholarly journals Prediction of the Effects of Synonymous Variants on SARS-CoV-2 Genome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1053
Author(s):  
Wan Xin Boon ◽  
Boon Zhan Sia ◽  
Chong Han Ng
Keyword(s):  
Codon Usage ◽  
Rna Structure ◽  
Rna Virus ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Viral Fitness ◽  
Translation Rate ◽  
Synonymous Mutations ◽  
Global Initiative ◽  
The Stability

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple studies had been done to identify and study nonsynonymous mutations, which change amino acid residues of SARS-CoV-2 proteins. On the other hand, there is little study on the effects of SARS-CoV-2 synonymous mutations. Although these mutations do not alter amino acids, some studies suggest that they may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome.   Methods: A total of 30,229 SARS-CoV-2 genomic sequences were retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database and aligned using MAFFT. Then, the mutations and their respective frequency were identified. A prediction of RNA secondary structures and their base pair probabilities was performed to study the effect of synonymous mutations on RNA structure and stability. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2.  Results: A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a, followed by C313U and C9286U mutation in nsp1 and nsp4 of ORF1a, respectively.   Conclusion: Among the synonymous mutations identified, C913U mutation in ORF1a and C26735U in membrane (M) protein may affect RNA secondary structure, reducing the stability of RNA folding and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

scholarly journals ΦX174 Attenuation by Whole Genome Codon Deoptimization

2020 ◽  
Author(s):  
James T Van Leuven ◽  
Martina M Ederer ◽  
Katelyn Burleigh ◽  
LuAnn Scott ◽  
Randall A Hughes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Viral Fitness ◽  
Live Attenuated Vaccine ◽  
Protein Coding ◽  
Viral Growth ◽  
Synonymous Mutations ◽  
Genes Encoding ◽  
Codon Deoptimization

Abstract Natural selection acting on synonymous mutations in protein-coding genes influences genome composition and evolution. In viruses, introducing synonymous mutations in genes encoding structural proteins can drastically reduce viral growth, providing a means to generate potent, live attenuated vaccine candidates. However, an improved understanding of what compositional features are under selection and how combinations of synonymous mutations affect viral growth is needed to predictably attenuate viruses and make them resistant to reversion. We systematically recoded all non-overlapping genes of the bacteriophage ΦX174 with codons rarely used in its E. coli host. The fitness of recombinant viruses decreases as additional deoptimizing mutations are made to the genome, although not always linearly, and not consistently across genes. Combining deoptimizing mutations may reduce viral fitness more or less than expected from the effect size of the constituent mutations and we point out difficulties in untangling correlated compositional features. We test our model by optimizing the same genes and find that the relationship between codon usage and fitness does not hold for optimization, suggesting that wild-type ΦX174 is at a fitness optimum. This work highlights the need to better understand how selection acts on patterns of synonymous codon usage across the genome and provides a convenient system to investigate the genetic determinants of virulence.

scholarly journals ΦX174 Attenuation by Whole Genome Codon Deoptimization

2020 ◽  
Author(s):  
James T. Van Leuven ◽  
Martina M. Ederer ◽  
Katelyn Burleigh ◽  
LuAnn Scott ◽  
Randall A. Hughes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Viral Fitness ◽  
Live Attenuated Vaccine ◽  
Protein Coding ◽  
Viral Growth ◽  
Synonymous Mutations ◽  
Genes Encoding ◽  
Codon Deoptimization

AbstractNatural selection acting on synonymous mutations in protein-coding genes influences genome composition and evolution. In viruses, introducing synonymous mutations in genes encoding structural proteins can drastically reduce viral growth, providing a means to generate potent, live attenuated vaccine candidates. However, an improved understanding of what compositional features are under selection and how combinations of synonymous mutations affect viral growth is needed to predictably attenuate viruses and make them resistant to reversion. We systematically recoded all non-overlapping genes of the bacteriophage ΦX174 with codons rarely used in its E. coli host. The fitness of recombinant viruses decreases as additional deoptimizing mutations are made to the genome, although not always linearly, and not consistently across genes. Combining deoptimizing mutations may reduce viral fitness more or less than expected from the effect size of the constituent mutations and we point out difficulties in untangling correlated compositional features. We test our model by optimizing the same genes and find that the relationship between codon usage and fitness does not hold for optimization, suggesting that wild-type ΦX174 is at a fitness optimum. This work highlights the need to better understand how selection acts on patterns of synonymous codon usage across the genome and provides a convenient system to investigate the genetic determinants of virulence.

scholarly journals Selection at the Amino Acid Level Can Influence Synonymous Codon Usage: Implications for the Study of Codon Adaptation in Plastid Genes

Genetics ◽  
2001 ◽  
Vol 159 (1) ◽  
pp. 347-358
Author(s):  
Brian R Morton
Keyword(s):  
Codon Usage ◽  
Synonymous Codon ◽  
Amino Acid Level ◽  
Synonymous Codon Usage ◽  
Noncoding Dna ◽  
Translation Rate ◽  
Coding Sequences ◽  
Synonymous Codons ◽  
Synonymous Sites ◽  
Translation Accuracy

Abstract A previously employed method that uses the composition of noncoding DNA as the basis of a test for selection between synonymous codons in plastid genes is reevaluated. The test requires the assumption that in the absence of selective differences between synonymous codons the composition of silent sites in coding sequences will match the composition of noncoding sites. It is demonstrated here that this assumption is not necessarily true and, more generally, that using compositional properties to draw inferences about selection on silent changes in coding sequences is much more problematic than commonly assumed. This is so because selection on nonsynonymous changes can influence the composition of synonymous sites (i.e., codon usage) in a complex manner, meaning that the composition biases of different silent sites, including neutral noncoding DNA, are not comparable. These findings also draw into question the commonly utilized method of investigating how selection to increase translation accuracy influences codon usage. The work then focuses on implications for studies that assess codon adaptation, which is selection on codon usage to enhance translation rate, in plastid genes. A new test that does not require the use of noncoding DNA is proposed and applied. The results of this test suggest that far fewer plastid genes display codon adaptation than previously thought.

Codon Usage Bias Covaries With Expression Breadth and the Rate of Synonymous Evolution in Humans, but This Is Not Evidence for Selection

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1191-1199
Author(s):  
Araxi O Urrutia ◽  
Laurence D Hurst
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Nucleotide Composition ◽  
Synonymous Codon Usage ◽  
Synonymous Substitutions ◽  
Numerous Species ◽  
Nucleotide Content ◽  
Expression Breadth ◽  
Human Genes

Abstract In numerous species, from bacteria to Drosophila, evidence suggests that selection acts even on synonymous codon usage: codon bias is greater in more abundantly expressed genes, the rate of synonymous evolution is lower in genes with greater codon bias, and there is consistency between genes in the same species in which codons are preferred. In contrast, in mammals, while nonequal use of alternative codons is observed, the bias is attributed to the background variance in nucleotide concentrations, reflected in the similar nucleotide composition of flanking noncoding and exonic third sites. However, a systematic examination of the covariants of codon usage controlling for background nucleotide content has yet to be performed. Here we present a new method to measure codon bias that corrects for background nucleotide content and apply this to 2396 human genes. Nearly all (99%) exhibit a higher amount of codon bias than expected by chance. The patterns associated with selectively driven codon bias are weakly recovered: Broadly expressed genes have a higher level of bias than do tissue-specific genes, the bias is higher for genes with lower rates of synonymous substitutions, and certain codons are repeatedly preferred. However, while these patterns are suggestive, the first two patterns appear to be methodological artifacts. The last pattern reflects in part biases in usage of nucleotide pairs. We conclude that we find no evidence for selection on codon usage in humans.

scholarly journals Effect of genome composition and codon bias on infectious bronchitis virus evolution and adaptation to target tissues

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giovanni Franzo ◽  
Claudia Maria Tucciarone ◽  
Matteo Legnardi ◽  
Mattia Cecchinato
Keyword(s):  
Codon Usage ◽  
Codon Bias ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Accessory Proteins ◽  
Effective Number ◽  
Genome Composition ◽  
Infectious Bronchitis ◽  
Selective Forces ◽  
Effective Number Of Codons

Abstract Background Infectious bronchitis virus (IBV) is one of the most relevant viruses affecting the poultry industry, and several studies have investigated the factors involved in its biological cycle and evolution. However, very few of those studies focused on the effect of genome composition and the codon bias of different IBV proteins, despite the remarkable increase in available complete genomes. In the present study, all IBV complete genomes were downloaded (n = 383), and several statistics representative of genome composition and codon bias were calculated for each protein-coding sequence, including but not limited to, the nucleotide odds ratio, relative synonymous codon usage and effective number of codons. Additionally, viral codon usage was compared to host codon usage based on a collection of highly expressed genes in IBV target and nontarget tissues. Results The results obtained demonstrated a significant difference among structural, non-structural and accessory proteins, especially regarding dinucleotide composition, which appears under strong selective forces. In particular, some dinucleotide pairs, such as CpG, a probable target of the host innate immune response, are underrepresented in genes coding for pp1a, pp1ab, S and N. Although genome composition and dinucleotide bias appear to affect codon usage, additional selective forces may act directly on codon bias. Variability in relative synonymous codon usage and effective number of codons was found for different proteins, with structural proteins and polyproteins being more adapted to the codon bias of host target tissues. In contrast, accessory proteins had a more biased codon usage (i.e., lower number of preferred codons), which might contribute to the regulation of their expression level and timing throughout the cell cycle. Conclusions The present study confirms the existence of selective forces acting directly on the genome and not only indirectly through phenotype selection. This evidence might help understanding IBV biology and in developing attenuated strains without affecting the protein phenotype and therefore immunogenicity.

scholarly journals The Effect of Multiple Evolutionary Selections on Synonymous Codon Usage of Genes in the Mycoplasma bovis Genome

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108949 ◽  
Author(s):  
Jian-hua Zhou ◽  
Yao-zhong Ding ◽  
Ying He ◽  
Yue-feng Chu ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Codon Usage ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Mycoplasma Bovis
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