scholarly journals Comparisons of Coding and Noncoding Sequences to infer the Origin of Codon usage Bias

2017 ◽  
Author(s):  
Prashant Mainali ◽  
Sobita Pathak
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Gc Content ◽  
Mutation Bias ◽  
Translation Process ◽  
Noncoding Regions ◽  
Coding Regions ◽  
Synonymous Codons ◽  
Shed Light

ABSTRACTCodon usage bias is the preferential use of the subset of synonymous codons during translation. In this paper, the comparisons of normalized entropy and GC content between the sequence of coding regions of Escherichia coli k12 and noncoding regions (ncRNA, rRNA) of various organisms were done to shed light on the origin of the codon usage bias.The normalized entropy of the coding regions was found significantly higher than the noncoding regions, suggesting the role of the translation process in shaping codon usage bias. Further, when the position specific GC content of both coding and noncoding regions was analyzed, the GC2 content in coding regions was lower than GC1 and GC2 while in noncoding regions, the GC1, GC2, GC3 contents were approximately equal. This discrepancy is explained by the biased mutation coupled with the presence and absence of selection pressure. The accumulation of CG content occurs in the sequences due to mutation bias in DNA repair and recombination process. In noncoding regions, the mutation is harmful and thus, selected against while due to the degeneracy of codons in coding regions, a mutation in GC3 is neutral and hence, not selected. Thus, the accumulation of GC content occurs in coding regions, and thus codon usage bias occurs.

scholarly journals Comprehensive Analysis and Comparison on the Codon Usage Pattern of Whole Mycobacterium tuberculosis Coding Genome from Different Area

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Li Gun ◽  
Ren Yumiao ◽  
Pan Haixian ◽  
Zhang Liang
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Gc Content ◽  
Codon Usage Pattern ◽  
Usage Pattern ◽  
Strong Negative Correlation ◽  
Synonymous Codons ◽  
The Relationship ◽  
Adaptation Index

Phenomenon of unequal use of synonymous codons in Mycobacterium tuberculosis is common. Codon usage bias not only plays an important regulatory role at the level of gene expression, but also helps in improving the accuracy and efficiency of translation. Meanwhile, codon usage pattern of Mycobacterium tuberculosis genome is important for interpreting evolutionary characteristics in species. In order to investigate the codon usage pattern of the Mycobacterium tuberculosis genome, 12 Mycobacterium tuberculosis genomes from different area are downloaded from the GeneBank. The correlations between G3, GC12, whole GC content, codon adaptation index, codon bias index, and so on of Mycobacterium tuberculosis genomes are calculated. The ENC-plot, relationship between A3/(A3+T3) and G3/(G3+C3), GC12 versus GC3 plot, and the RSCU of overall/separated genomes all show that the codon usage bias exists in all 12 Mycobacterium tuberculosis genomes. Lastly, relationship between CBI and the equalization of ENC shows a strong negative correlation between them. The relationship between protein length and GC content (GC3 and GC12) shows that more obvious differences in the GC content may be in shorter protein. These results show that codon usage bias existing in the Mycobacterium tuberculosis genomes could be used for further study on their evolutionary phenomenon.

scholarly journals Position-dependent Codon Usage Bias in the Human Transcriptome

2021 ◽  
Author(s):  
Kaavya Subramanian ◽  
Nathan Waugh ◽  
Cole Shanks ◽  
David A Hendrix
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Gc Content ◽  
Nervous System Development ◽  
Functional Enrichment ◽  
Translational Efficiency ◽  
Chemical Stimulus ◽  
Human Transcriptome ◽  
Coding Regions ◽  
Coding Potential

All life depends on the reliable translation of RNA to protein according to complex interactions between translation machinery and RNA sequence features. While ribosomal occupancy and codon frequencies vary across coding regions, well-established metrics for computing coding potential of RNA do not capture such positional dependence. Here, we investigate position-dependent codon usage bias (PDCUB), which dynamically accounts for the position of protein-coding signals embedded within coding regions. We demonstrate the existence of PDCUB in the human transcriptome, and show that it can be used to predict translation-initiating codons with greater accuracy than other models. We further show that observed PDCUB is not accounted for by other common metrics, including position-dependent GC content, consensus sequences, and the presence of signal peptides in the translation product. More importantly, PDCUB defines a spectrum of translational efficiency supported by ribosomal occupancy and tRNA adaptation index (tAI). High PDCUB scores correspond to a tAI-defined translational ramp and low ribosomal occupancy, while low PDCUB scores exhibit a translational valley and the highest ribosomal occupancy. Finally, we examine the relationship between PDCUB intensity and functional enrichment. We find that transcripts with start codons showing the highest PDCUB are enriched for functions relating to the regulation of synaptic signaling and plasticity, as well as skeletal, heart, and nervous-system development. Furthermore, transcripts with high PDCUB are depleted for functions related to immune response and detection of chemical stimulus. These findings lay important groundwork for advances in our understanding of the regulation of translation, the calculation of coding potential, and the classification of RNA transcripts.

Analysis of Codon Usage in Herpesvirus Glycoprotein B (gB) Gene

2011 ◽  
Vol 343-344 ◽  
pp. 721-728
Author(s):  
Long Jiang ◽  
An Chun Cheng ◽  
Ming Shu Wang ◽  
De Kang Zhu ◽  
Ren Yong Jia
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Codon Position ◽  
Pearson Correlation ◽  
Gc Content ◽  
Correlation Coefficients ◽  
Mutational Bias ◽  
Synonymous Codons ◽  
Base Position ◽  
Two Factors

Due to the degeneracy of genetic code, most amino acids are coded by more than one codon (synonymous codons). The synonymous codons are not used at equal frequencies both within and between organisms. Of the total 33 herpesvirus gB genes, approximately 9.1% of the total gB genes had low codon bias (ENC<35), 72.7% of the gB genes had high ENC values (ENC>50), indicating that these gB genes had random codon usage in herpesviruses. There might be no direct correlation between the codon usage bias and the host, which indicates that the tRNA abundance of the host was not the main factor influencing the codon usage bias. A plot of ENC vs. GC3 indicates that mutational bias may be a more important factor than tRNA abundance in determining codon usage bias of herpesvirus gB genes. Pearson correlation coefficients between the ENC value and corresponding GC%, cumulative GC% in 2nd (GC2%) and 3rd codon position (GC3%) of each herpesvirus gB gene were -0.621 (p<0.01), -0.656 (p<0.01) and -0.712 (p<0.01), respectively, which implies that significant correlations existed between them. But no significant correlations existed between ENC and cumulative GC% in 1st codon position of each herpesviral gB gene. Furthermore, significant correlations also existed between GC% and GC3% of 33 herpesvirus gB genes (r=0.856, p<0.01). So it seems that, GC content, and particularly GC content at the 3rd base position, contributing greatly to the effective number of codons, indicating that the mutational bias dominates over translational selection. Further analysis on the relationship between gene length and ENC of 33 herpesvirus gB genes demonstrated that the two factors were not correlated. Significant correlations were found between the gene expression levels assessed by CAI value and ENC (r = -0.424, p<0.05) and GC3 values (r = 0.644, p<0.01).

scholarly journals Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in Hemagglutinin Gene in H1N1 Subtype of InfluenzaAVirus

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Himangshu Deka ◽  
Supriyo Chakraborty
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Viral Evolution ◽  
Gc Content ◽  
H1n1 Subtype ◽  
Evolutionary Forces ◽  
Viral Hemagglutinin ◽  
Compositional Constraint

It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. InfluenzaAvirus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenzaAviruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenzaAvirus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences wereAredundant with most codons preferring nucleotideAover others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus.

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 The Evolution of Isochores: Evidence From SNP Frequency Distributions

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst
Keyword(s):  
Population Genetics ◽  
Large Scale ◽  
Gc Content ◽  
Nucleotide Composition ◽  
Compositional Variation ◽  
Mutation Bias ◽  
Single Nucleotide ◽  
Frequency Distributions ◽  
Noncoding Regions ◽  
Standard Population

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.

Comparative analysis of codon usage patterns in SARS-CoV-2, its mutants and other respiratory viruses

2021 ◽  
Author(s):  
Neetu Tyagi ◽  
Rahila Sardar ◽  
Dinesh Gupta
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Gc Content ◽  
Respiratory Illness ◽  
Respiratory Viruses ◽  
Nucleotide Composition ◽  
Health Crisis ◽  
Study Results ◽  
Usage Patterns ◽  
The Difference

AbstractThe Coronavirus disease 2019 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) poses a worldwide human health crisis, causing respiratory illness with a high mortality rate. To investigate the factors governing codon usage bias in all the respiratory viruses, including SARS-CoV-2 isolates from different geographical locations (~62K), including two recently emerging strains from the United Kingdom (UK), i.e., VUI202012/01 and South Africa (SA), i.e., 501.Y.V2 codon usage bias (CUBs) analysis was performed. The analysis includes RSCU analysis, GC content calculation, ENC analysis, dinucleotide frequency and neutrality plot analysis. We were motivated to conduct the study to fulfil two primary aims: first, to identify the difference in codon usage bias amongst all SARS-CoV-2 genomes and, secondly, to compare their CUBs properties with other respiratory viruses. A biased nucleotide composition was found as most of the highly preferred codons were A/U-ending in all the respiratory viruses studied here. Compared with the human host, the RSCU analysis led to the identification of 11 over-represented codons and 9 under-represented codons in SARS-CoV-2 genomes. Correlation analysis of ENC and GC3s revealed that mutational pressure is the leading force determining the CUBs. The present study results yield a better understanding of codon usage preferences for SARS-CoV-2 genomes and discover the possible evolutionary determinants responsible for the biases found among the respiratory viruses, thus unveils a unique feature of the SARS-CoV-2 evolution and adaptation. To the best of our knowledge, this is the first attempt at comparative CUBs analysis on the worldwide genomes of SARS-CoV-2, including novel emerged strains and other respiratory viruses.

scholarly journals Coupling Between Protein Level Selection and Codon Usage Optimization in the Evolution of Bacteria and Archaea

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Wenqi Ran ◽  
David M. Kristensen ◽  
Eugene V. Koonin
Keyword(s):  
Codon Usage ◽  
Protein Level ◽  
Codon Usage Bias ◽  
Protein Sequence ◽  
Gc Content ◽  
Protein Sequences ◽  
Microbial Evolution ◽  
Fine Tuning ◽  
Selection For ◽  
Genomic Gc Content

ABSTRACT The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (F opt ) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between F opt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, “high-status” genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution. IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both the structure of proteins and the regulation of their production. Here we demonstrate the coupling between the selection on protein sequences and the optimization of codon usage in a broad range of bacteria and archaea. The strength of this coupling varies over a wide range and strongly and positively correlates with the genomic GC content. The cause(s) of the evolution of high GC content is a long-standing open question, given the universal mutational bias toward AT. We propose that optimization of codon usage could be one of the key factors that determine the evolution of GC-rich genomes. This work establishes the coupling between selection at the level of protein sequence and at the level of codon choice optimization as a distinct aspect of genome evolution.

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 codon usage bias of classical swine fever virus

2021 ◽  
pp. 1450-1458
Author(s):  
Sharanagouda S. Patil ◽  
Uma Bharathi Indrabalan ◽  
Kuralayanapalya Puttahonnappa Suresh ◽  
Bibek Ranjan Shome
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Synonymous Codon ◽  
Principal Component ◽  
Infectious Agent ◽  
Classical Swine Fever ◽  
Economic Loss ◽  
Codon Usage Pattern ◽  
Usage Pattern ◽  
Coding Regions

Background and Aim: Classical swine fever (CSF), caused by CSF virus (CSFV), is a highly contagious disease in pigs causing 100% mortality in susceptible adult pigs and piglets. High mortality rate in pigs causes huge economic loss to pig farmers. CSFV has a positive-sense RNA genome of 12.3 kb in length flanked by untranslated regions at 5' and 3' end. The genome codes for a large polyprotein of 3900 amino acids coding for 11 viral proteins. The 1300 codons in the polyprotein are coded by different combinations of three nucleotides which help the infectious agent to evolve itself and adapt to the host environment. This study performed and employed various methods/techniques to estimate the changes occurring in the process of CSFV evolution by analyzing the codon usage pattern. Materials and Methods: The evolution of viruses is widely studied by analyzing their nucleotides and coding regions/ codons using various methods. A total of 115 complete coding regions of CSFVs including one complete genome from our laboratory (MH734359) were included in this study and analysis was carried out using various methods in estimating codon usage bias and evolution. This study elaborates on the factors that influence the codon usage pattern. Results: The effective number of codons (ENC) and relative synonymous codon usage showed the presence of codon usage bias. The mononucleotide (A) has a higher frequency compared to the other mononucleotides (G, C, and T). The dinucleotides CG and CC are underrepresented and overrepresented. The codons CGT was underrepresented and AGG was overrepresented. The codon adaptation index value of 0.71 was obtained indicating that there is a similarity in the codon usage bias. The principal component analysis, ENC-plot, Neutrality plot, and Parity Rule 2 plot produced in this article indicate that the CSFV is influenced by the codon usage bias. The mutational pressure and natural selection are the important factors that influence the codon usage bias. Conclusion: The study provides useful information on the codon usage analysis of CSFV and may be utilized to understand the host adaptation to virus environment and its evolution. Further, such findings help in new gene discovery, design of primers/probes, design of transgenes, determination of the origin of species, prediction of gene expression level, and gene function of CSFV. To the best of our knowledge, this is the first study on codon usage bias involving such a large number of complete CSFVs including one sequence of CSFV from India.

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