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

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.

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

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.641-642.654 ◽

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.

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Comparative analysis of codon usage patterns of FUT2 from different species

Kuwait Journal of Science ◽

10.48129/kjs.11289 ◽

2021 ◽

Author(s):

Chao Xu ◽

◽

Wen B. Bao ◽

Sheng L. Wu ◽

Zheng C. Wu ◽

...

Keyword(s):

Codon Usage ◽

Codon Usage Bias ◽

Molecular Mechanisms ◽

Synonymous Codon ◽

Synonymous Codon Usage ◽

Relative Synonymous Codon Usage ◽

Effective Number ◽

E Coli ◽

Effective Number Of Codons ◽

Fut2 Gene

Enterotoxigenic E. coli is an important zoonotic pathogen causing diarrhea in human and newborn animals. α - (1,2) fucosyltransferase 2 (FUT2) is closely associated with the formation of pathogenic receptors of Enterotoxigenic E. coli. Codon usage bias analysis can help to better understand the molecular mechanisms and evolutionary relationships of a particular gene. In order to understand the codon usage pattern of FUT2 gene, FUT2 gene coding sequences of nine species were selected from GenBank database for calculating the nucleotide composition (GC content) and genetic indices including effective number of codons, relative synonymous codon usage and relative codon usage bias using R software, in order to analyze codon usage bias and base composition in FUT2 gene from different species. The results showed that the codon usage of FUT2 gene in different species was affected by GC bias, especially GC frequency at the third position of codon (GC3). Most of the optimal codons were biased towards the G/C-ending types. GCC, CUG, UCC, GUG and AUC showed the highest relative synonymous codon usage value among different species, belonging to the most dominant codons. The usage characteristic of the codens for FUT2 gene in Sus scrofa was similar to that of Bos taurus; Homo sapiens was similar to Pan troglodytes. Effective number of codons was significantly, negatively correlated with GC3, and the relative higher frequency of optimal codon implied that FUT2 genes from different species had a strong bias in codon usage.

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

Genetics ◽

10.1093/genetics/159.3.1191 ◽

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.

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Intragenomic variation in mutation biases causes underestimation of selection on synonymous codon usage

10.1101/2021.10.29.466462 ◽

2021 ◽

Author(s):

Alexander L Cope ◽

Premal Shah

Keyword(s):

Population Genetics ◽

Natural Selection ◽

Codon Usage ◽

Codon Bias ◽

Synonymous Codon ◽

Synonymous Codon Usage ◽

Mutation Bias ◽

Biased Gene Conversion ◽

Intragenomic Variation ◽

The Impact

Patterns of non-uniform usage of synonymous codons (codon bias) varies across genes in an organism and across species from all domains of life. The bias in codon usage is due to a combination of both non-adaptive (e.g. mutation biases) and adaptive (e.g. natural selection for translation efficiency/accuracy) evolutionary forces. Most population genetics models quantify the effects of mutation bias and selection on shaping codon usage patterns assuming a uniform mutation bias across the genome. However, mutation biases can vary both along and across chromosomes due to processes such as biased gene conversion, potentially obfuscating signals of translational selection. Moreover, estimates of variation in genomic mutation biases are often lacking for non-model organisms. Here, we combine an unsupervised learning method with a population genetics model of synonymous codon bias evolution to assess the impact of intragenomic variation in mutation bias on the strength and direction of natural selection on synonymous codon usage across 49 Saccharomycotina budding yeasts. We find that in the absence of a priori information, unsupervised learning approaches can be used to identify regions evolving under different mutation biases. We find that the impact of intragenomic variation in mutation bias varies widely, even among closely-related species. We show that the overall strength and direction of selection on codon usage can be underestimated by failing to account for intragenomic variation in mutation biases. Interestingly, genes falling into clusters identified by machine learning are also often physically clustered across chromosomes, consistent with processes such as biased gene conversion. Our results indicate the need for more nuanced models of sequence evolution that systematically incorporate the effects of variable mutation biases on codon frequencies.

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Host Adaptation of Codon Usage in SARS-CoV-2 From Mammals Indicate Natural Selection

10.21203/rs.3.rs-1125942/v1 ◽

2021 ◽

Author(s):

Yanan Fu ◽

Yanping Huang ◽

Jingjing Rao ◽

Feng Zeng ◽

Ruiping Yang ◽

...

Keyword(s):

Natural Selection ◽

Codon Usage ◽

Binding Affinity ◽

Codon Bias ◽

Synonymous Codon ◽

Host Adaptation ◽

Synonymous Codon Usage ◽

Mutation Pressure ◽

Usage Analysis ◽

Human Receptor

Abstract The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 selects and evolves in the host, and the differences in the evolution of different animals are still unclear. To analysis the mutation and codon usage bias of SARS-CoV-2 in infected humans and animals. The SARS-CoV-2 sequence in mink (Mink-SARS2) and binding energy with receptor were calculated compared with human. The relative synonymous codon usage of viral encoded gene was analyzed to characterize the differences and the evolutionary characteristics. A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all of the animals showed decreased adaptability relative to that of humans, except for mink. The neutrality plot showed that the effect of natural selection on different SARS-CoV-2 sequences is stronger than mutation pressure. A binding affinity analysis indicated that the spike protein of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and N501T in Mink-SARS2 lead to improvement of binding affinity for mink receptor. In summary, mutations Y453F and N501T in Mink-SARS2 lead to improvement of binding affinity with mink receptor, indicating possible natural selection and current host adaptation. Monitoring the variation and codon bias of SARS-CoV-2 provides a theoretical basis for tracing the epidemic, evolution and cross-species spread of SARS-CoV-2.

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Codon Usage in the Iflaviridae Family Is Not Diverse Though the Family Members Are Isolated from Diverse Host Taxa

Viruses ◽

10.3390/v11121087 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1087 ◽

Cited By ~ 2

Author(s):

Sheng-Lin Shi ◽

Run-Xi Xia

Keyword(s):

Codon Usage ◽

Codon Usage Bias ◽

Synonymous Codon ◽

Nucleotide Composition ◽

Effective Number ◽

Bias Analysis ◽

The Family ◽

Usage Patterns ◽

Codon Positions ◽

Effective Number Of Codons

All iflavirus members belong to the unique genus, Iflavirus, of the family, Iflaviridae. The host taxa and sequence identities of these viruses are diverse. A codon usage bias, maintained by a balance between selection, mutation, and genetic drift, exists in a wide variety of organisms. We characterized the codon usage patterns of 44 iflavirus genomes that were isolated from the classes, Insecta, Arachnida, Mammalia, and Malacostraca. Iflaviruses lack a strong codon usage bias when they are evaluated using an effective number of codons. The odds ratios of the majority of dinucleotides are within the normal range. However, the dinucleotides at the 1st–2nd codon positions are more biased than those at the 2nd–3rd codon positions. Plots of effective numbers of codons, relative neutrality analysis, and PR2 bias analysis all indicate that selection pressure dominates mutations in shaping codon usage patterns in the family, Iflaviridae. When these viruses were grouped into their host taxa, we found that the indices, including the nucleotide composition, effective number of codons, relative synonymous codon usage, and the influencing factors behind the codon usage patterns, all show that there are non-significant differences between the six host-taxa-groups. Our results disagree with our assumption that diverse viruses should possess diverse codon usage patterns, suggesting that the nucleotide composition and codon usage in the family, Iflaviridae, are not host taxa-specific signatures.

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Evolutionary Pressures and Codon Bias in Low Complexity Regions of Plasmodia Parasites

10.1101/2020.03.14.992107 ◽

2020 ◽

Author(s):

Andrea Cappannini ◽

Sergio Forcelloni ◽

Andrea Giansanti

Keyword(s):

Evolutionary Biology ◽

Codon Bias ◽

Ad Hoc ◽

Selective Pressure ◽

Synonymous Codon ◽

Plasmodium Species ◽

Low Complexity ◽

Synonymous Codon Usage ◽

Host Proteins ◽

Effective Number Of Codons

AbstractOne of the most debated topics in Evolutionary Biology concerns Low Complexity Regions of P. falciparum, the causative agent of the most virulent and deadly form of human malaria. In this work, we analysed the proteome of 22 plasmodium species including P. falciparum. SEG predicts that proteins containing Low Complexity Regions turn out to be longer than those which are predicted to be completely complex (without Low Complexity Regions). Moreover, using some well-known bioinformatics tools such as the Effective Number of Codons, the Pr2 and a new index that we have called SPI, we have noticed how proteins that embed Low Complexity Regions are under lower selective pressure than those that do not present this type of locus. By applying the Relative Synonymous Codon Usage and other tools developed ad hoc for this study, we note, instead, how the Low Complexity Regions appear to have a non-neutral codon bias with respect to the host proteins.

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Analysis of synonymous codon usage in spike protein gene of infectious bronchitis virus

Canadian Journal of Microbiology ◽

10.1139/cjm-2015-0418 ◽

2015 ◽

Vol 61 (12) ◽

pp. 983-989 ◽

Cited By ~ 3

Author(s):

Aditi Makhija ◽

Sachin Kumar

Keyword(s):

Codon Usage ◽

Infectious Bronchitis Virus ◽

Codon Usage Bias ◽

Synonymous Codon ◽

Synonymous Codon Usage ◽

Spike Protein ◽

Economic Losses ◽

Infectious Bronchitis ◽

S Gene ◽

S Genes

Infectious bronchitis virus (IBV) is responsible for causing respiratory, renal, and urogenital diseases in poultry. IBV infection in poultry leads to high mortality rates in affected flocks and to severe economic losses due to a drop in egg production and a reduced gain in live weight of the broiler birds. IBV-encoded spike protein (S) is the major protective immunogen for the host. Although the functions of the S protein have been well studied, the factors shaping synonymous codon usage bias and nucleotide composition in the S gene have not been reported yet. In the present study, we analyzed the relative synonymous codon usage and effective number of codons (Nc) using the 53 IBV S genes. The major trend in codon usage variation was studied using correspondence analysis. The plot of Nc values against GC3 as well as the correlation between base composition and codon usage bias suggest that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in the S gene. Interestingly, no association of aromaticity, degree of hydrophobicity, and aliphatic index was observed with the codon usage variation in IBV S genes. The study represents a comprehensive analysis of IBV S gene codon usage patterns and provides a basic understanding of the codon usage bias.

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The complete chloroplast genome sequence of Morus cathayana and Morus multicaulis, and comparative analysis within genus Morus L

PeerJ ◽

10.7717/peerj.3037 ◽

2017 ◽

Vol 5 ◽

pp. e3037 ◽

Cited By ~ 11

Author(s):

Wei Qing Kong ◽

Jin Hong Yang

Keyword(s):

Codon Usage ◽

Evolutionary Biology ◽

Synonymous Codon ◽

Synonymous Codon Usage ◽

Mutational Bias ◽

Coding Region ◽

Variable Regions ◽

Standard Curve ◽

Gene Coding ◽

Effective Number Of Codons

Trees in the Morus genera belong to the Moraceae family. To better understand the species status of genus Morus and to provide information for studies on evolutionary biology within the genus, the complete chloroplast (cp) genomes of M. cathayana and M. multicaulis were sequenced. The plastomes of the two species are 159,265 bp and 159,103 bp, respectively, with corresponding 83 and 82 simple sequence repeats (SSRs). Similar to the SSRs of M. mongolica and M. indica cp genomes, more than 70% are mononucleotides, ten are in coding regions, and one exhibits nucleotide content polymorphism. Results for codon usage and relative synonymous codon usage show a strong bias towards NNA and NNT codons in the two cp genomes. Analysis of a plot of the effective number of codons (ENc) for five Morus spp. cp genomes showed that most genes follow the standard curve, but several genes have ENc values below the expected curve. The results indicate that both natural selection and mutational bias have contributed to the codon bias. Ten highly variable regions were identified among the five Morus spp. cp genomes, and 154 single-nucleotide polymorphism mutation events were accurately located in the gene coding region.

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The Effects of the Context-Dependent Codon Usage Bias on the Structure of the nsp1αof Porcine Reproductive and Respiratory Syndrome Virus

BioMed Research International ◽

10.1155/2014/765320 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yao-zhong Ding ◽

Ya-nan You ◽

Dong-jie Sun ◽

Hao-tai Chen ◽

Yong-lu Wang ◽

...

Keyword(s):

Codon Usage ◽

Codon Bias ◽

Structural Information ◽

Synonymous Codon ◽

Data Bank ◽

Synonymous Codon Usage ◽

Respiratory Syndrome Virus ◽

Translation Speed ◽

Context Dependent ◽

Insight Into

The information about the crystal structure of porcine reproductive and respiratory syndrome virus (PRRSV) leader protease nsp1αis available to analyze the roles of tRNA abundance of pigs and codon usage of thensp1αgene in the formation of this protease. The effects of tRNA abundance of the pigs and the synonymous codon usage and the context-dependent codon bias (CDCB) of thensp1αon shaping the specific folding units (α-helix,β-strand, and the coil) in the nsp1αwere analyzed based on the structural information about this protease from protein data bank (PDB: 3IFU) and thensp1αof the 191 PRRSV strains. By mapping the overall tRNA abundance along thensp1α, we found that there is no link between the fluctuation of the overall tRNA abundance and the specific folding units in the nsp1α, and the low translation speed of ribosome caused by the tRNA abundance exists in thensp1α. The strong correlation between some synonymous codon usage and the specific folding units in the nsp1αwas found, and the phenomenon of CDCB exists in the specific folding units of the nsp1α. These findings provide an insight into the roles of the synonymous codon usage and CDCB in the formation of PRRSV nsp1αstructure.

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