Extent Of Codon Usage Bias Research Articles

Codon usage bias of goose circovirus and its adaptation to host

Goose circovirus (GoCV), a potential immunosuppressive virus possessing a circular single-stranded DNA genome, is widely distributed in both domesticated and wild geese. This virus infection causes significant economic losses in the waterfowl industry. The codon usage patterns of viruses reflect the evolutionary history and genetic architecture, allowing them to adapt quickly to changes in the external environment, particularly to their hosts. In this study, we retrieved the coding sequences (Rep and Cap) and the genome of GoCV from GenBank, conducting comprehensive research to explore the codon usage patterns in 144 GoCV strains. The overall codon usage of the GoCV strains was relatively similar and exhibited a slight bias. The effective number of codons (ENC) indicated a low overall extent of codon usage bias (CUB) in GoCV. Combined with the base composition and relative synonymous codon usage (RSCU) analysis, the results revealed a bias toward A- and G-ending codons in the overall codon usage. Analysis of the ENC-GC3s plot and neutrality plot suggested that natural selection plays an important role in shaping the codon usage pattern of GoCV, with mutation pressure having a minor influence. Furthermore, the correlations between ENC and relative indices, as well as correspondence analysis (COA), showed that hydrophobicity and geographical distribution also contribute to codon usage variation in GoCV, suggesting the possible involvement of natural selection. In conclusion, GoCV exhibits comparatively slight CUB, with natural selection being the major factor shaping the codon usage pattern of GoCV. Our research contributes to a deeper understanding of GoCV evolution and its host adaptation, providing valuable insights for future basic studies and vaccine design related to GoCV.

Deep decoding of codon usage strategies and host adaption preferences of soybean mosaic virus

Soybean mosaic virus (SMV) has threatened the global yield of Leguminosae crops, but the mechanism of its infection, spread, and evolution remains unknown. A systemic analysis of 107 SMV strains was performed to explore the genome-wide codon usage profile and the various factors influencing the codon usage patterns of SMV, which provides insight into its molecular evolution and elucidates its unknown host adaptation pattern. The overall nucleotide composition and correlation analysis revealed that the preferred synonymous codons mostly end with A/U. Clustering by RSCU value of each strain and phylogenetic tree analysis showed that the SMV isolates studied were divided into four clades, with a low overall extent of codon usage bias (CUB) in SMV. According to the ENC, PR2, neutrality plot, and correspondence analysis, natural selection of geographical diversity may play a critical role in the CUB. Higher adaptability was shown in Glycine with SMV and more pressure was received by clade III. These findings could not only provide valuable information about the overall codon usage pattern of the SMV genome, but could also aid in the clarification of the involved mechanisms that dominate the codon usage patterns and genetic evolution of the SMV genome.

Codon usage pattern and its influencing factors in different genomes of hepadnaviruses.

Codon usage bias (CUB) arises from the preference for a codon over codons for the same amino acid. The major factors contributing to CUB are evolutionary forces, compositional properties, gene expression, and protein properties. The present analysis was performed to investigate the compositional properties and the extent of CUB across the genomes of members of the family Hepadnaviridae, as previously no work using bioinformatic tools has been reported. The viral genes were found to be AT rich with low CUB. Analysis of relative synonymous codon usage (RSCU) was used to identify overrepresented and underrepresented codons for each amino acid. Correlation analysis of overall nucleotide composition and its composition at the third codon position suggested that mutation pressure might influence the CUB. A highly significant correlation was observed between GC12 and GC3 (r = 0.910, p < 0.01), indicating that directional mutation affected all three codon positions across the genome. Translational selection (P2) and mutational responsive index (MRI) values of genes suggested that mutation plays a more important role than translational selection in members of the family Hepadnaviridae.Electronic supplementary materialThe online version of this article (10.1007/s00705-020-04533-6) contains supplementary material, which is available to authorized users.

Analysis of Synonymous Codon Usage Bias in Flaviviridae Virus.

Background Flaviviridae viruses are single-stranded, positive-sense RNA viruses, which threat human constantly mediated by mosquitoes, ticks, and sandflies. Considering the recent increase in the prevalence of the family virus and its risk potential, we investigated the codon usage pattern to understand its evolutionary processes and provide some useful data to develop the medications for most of Flaviviridae viruses. Results The overall extent of codon usage bias in 65 Flaviviridae viruses is low with the average value of GC contents being 50.5% and the highest value being 55.9%; the lowest value is 40.2%. ENC values of Flaviviridae virus genes vary from 48.75 to 57.83 with a mean value of 55.56. U- and A-ended codons are preferred in the Flaviviridae virus. Correlation analysis shows that the positive correlation between ENC value and GC content at the third nucleotide positions was significant in this family virus. The result of analysis of ENC, neutrality plot analysis, and correlation analysis revealed that codon usage bias of all the viruses was affected mainly by natural selection. Meanwhile, according to correspondence analysis (CoA) based on RSCU and phylogenetic analysis, the Flaviviridae viruses mainly are made up of two groups, Group I (Yellow fever virus, Apoi virus, Tembusu virus, Dengue virus 1, and others) and Group II (West Nile virus lineage 2, Japanese encephalitis virus, Usutu virus, Kedougou virus, and others). Conclusions All in, the bias of codon usage pattern is affected not only by compositional constraints but also by natural selection. Phylogenetic analysis also illustrates that codon usage bias of virus can serve as an effective means of evolutionary classification in Flaviviridae virus.

Comprehensive analysis of the codon usage patterns of polyprotein of Zika virus

Zika virus (ZIKV) is a mosquito-borne virus in the family Flaviviridae, and the massive outbreak of ZIKV has endangered public health. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. In this study, 90 ZIKV isolates were used for a comprehensive analysis on the codon usage patterns. The overall codon usage among ZIKV strains is similar and slightly biased. The value of effective number of codons (ENC) showed that the overall extent of codon usage bias in ZIKV is relatively low. Nucleotide analysis showed that the overall codon usage is biased toward A- and G-ending codons. The phylogenetic analysis indicated that their independent evolutionary origins from a common ancestor. The RSCU analysis showed that the codon usage pattern of ZIKV is more similar to that of Homo sapiens. Correlation analysis, Correspondence analysis, ENC-GC3S plot, and PR2 plot indicated that the codon usage patterns of the viruses are not only influenced by mutational pressure but also by natural selection, but neutrality plot analysis showed that the latter plays a major role. These results built the base for further research on the molecular evolution of ZIKV.

The codon usage pattern of genes involved in ovarian cancer.

In this study, we analyzed the compositional dynamics and codon usage pattern of genes involved in ovarian cancer (OC) using a computational method. Mutations in specific genes are associated with OC, and some genes are risk factors for progression of OC, but no work has been reported yet on the codon usage pattern of genes involved in OC. Nucleotide composition analysis of OC-related genes suggested that the overall GC content was higher than AT content; that is, the genes were GC rich. The improved effective number of codons indicated that the overall extent of codon usage bias of genes involved in OC was low. The codons AGC, CTG, ATC, ACC, GTG, and GCC were overrepresented, while the codons TCG, TTA, CTA, CCG, CAA, CGT, ATA, ACG, GTA, GTT, GCG, and GGT were underrepresented in the genes. Correspondence analysis suggested that the codon usage pattern was different in different genes. A highly significant correlation was observed between GC12 and GC3 (r = 0.587, P < 0.01) of genes, suggesting that directional mutation affected the three codon positions. Our report on the codon usage pattern of genes involved in OC includes a new perspective for elucidating the mechanisms of biased usage of synonymous codons, as well as providing useful clues for molecular genetic engineering.

Analysis of synonymous codon usage in Zika virus

Zika virus is a zoonotic pathogen, which have made frequent incursion into the human population in Africa and South East Asia over the course of several decades but never reached to the pandemic proportions until the most recent outbreak. Viruses are solely dependent on host synthetic machinery for their replication cycle; therefore, replication and persistence in a host species of different genetic background requires certain degree of adaptation. These adaptations are necessary to avoid detection from host immune surveillance and maximize the utilization of available resources for efficient viral replication. Study of genomic composition and codon usage pattern not only offer an insight into the adaptation of viruses to their new host, but may also provide some information about pathogenesis and spread of the virus. To elucidate the genetic features and synonymous codon usage bias in ZIKV genome, a comprehensive analysis was performed on 80 full-length ZIKV sequences. Our analyses shows that the overall extent of codon usage bias in ZIKV genome is low and affected by nucleotide composition, protein properties, natural selection, and gene expression level.

What PEEP level should I use in my patient?

Zika virus is a zoonotic pathogen, which have made frequent incursion into the human population in Africa and South East Asia over the course of several decades but never reached to the pandemic proportions until the most recent outbreak. Viruses are solely dependent on host synthetic machinery for their replication cycle; therefore, replication and persistence in a host species of different genetic background requires certain degree of adaptation. These adaptations are necessary to avoid detection from host immune surveillance and maximize the utilization of available resources for efficient viral replication. Study of genomic composition and codon usage pattern not only offer an insight into the adaptation of viruses to their new host, but may also provide some information about pathogenesis and spread of the virus. To elucidate the genetic features and synonymous codon usage bias in ZIKV genome, a comprehensive analysis was performed on 80 full-length ZIKV sequences. Our analyses shows that the overall extent of codon usage bias in ZIKV genome is low and affected by nucleotide composition, protein properties, natural selection, and gene expression level.

Codon usage bias and its influencing factors for Y-linked genes in human

The non-uniform usage of synonymous codons during translation of a protein is the codon usage bias and is mainly influenced by natural selection and mutation pressure. We have used bioinformatic approaches to analyze codon usage bias of human Y-linked genes. Effective number of codon (ENC) suggested that the overall extent of codon usage bias of genes was low. The relative synonymous codon usage (RSCU) analysis revealed that AGA and CTG codons were over-represented in Y-linked genes. Compositional constraint under mutation pressure influenced the codon usage pattern as revealed by the correspondence analysis (COA). Parity plot suggests that both natural selection and mutation pressure might have influenced the codon usage bias of Y-linked genes.

Gene expression, nucleotide composition and codon usage bias of genes associated with human Y chromosome.

Analysis of codon usage pattern is important to understand the genetic and evolutionary characteristics of genomes. We have used bioinformatic approaches to analyze the codon usage bias (CUB) of the genes located in human Y chromosome. Codon bias index (CBI) indicated that the overall extent of codon usage bias was low. The relative synonymous codon usage (RSCU) analysis suggested that approximately half of the codons out of 59 synonymous codons were most frequently used, and possessed a T or G at the third codon position. The codon usage pattern was different in different genes as revealed from correspondence analysis (COA). A significant correlation between effective number of codons (ENC) and various GC contents suggests that both mutation pressure and natural selection affect the codon usage pattern of genes located in human Y chromosome. In addition, Y-linked genes have significant difference in GC contents at the second and third codon positions, expression level, and codon usage pattern of some codons like the SPANX genes in X chromosome.

Nucleotide composition and codon usage bias of SRY gene.

The SRY gene is present within the sex-determining region of the Y chromosome which is responsible for maleness in mammals. The nonuniform usage of synonymous codons in the mRNA transcript for encoding a particular amino acid is the codon usage bias (CUB). Analysis of codon usage pattern is important to understand the genetic and molecular organisation of a gene. It also helps in heterologous gene expression, design of primer and synthetic gene. However, the analysis of codon usage bias of SRY gene was not yet studied. We have used bioinformatic tools to analyse codon usage bias of SRY gene across mammals. Codon bias index (CBI) indicated that the overall extent of codon usage bias was weak. The relative synonymous codon usage (RSCU) analysis suggested that most frequently used codons had an A or C at the third codon position. Compositional constraint played an important role in codon usage pattern as evident from correspondence analysis (CA). Significant correlation among nucleotides constraints indicated that both mutation pressure and natural selection affect the codon usage pattern. Neutrality plot suggested that natural selection might play a major role, while mutation pressure might play a minor role in codon usage pattern in SRY gene in different species of mammals.

Phylogenetic Analysis of Coxsackie B Viruses Reveals Genomic Plasticity and Adaptation as Studied by Codon Usage Patterns

Coxsackie B viruses (CVB) are associated with serious illnesses in humans. In this study, the patterns of synonymous codon usage in CVB have been studied through multivariate statistical methods. Effective number of codons (ENC) indicates that the overall extent of codon usage bias in CVB is not significant. The relative dinucleotide abundances suggest that codon usage bias in CVB genomes is influenced by underlying biases of dinucleotide frequencies. The distribution of CVB ORFs along the plane defined by the first two axes of correspondence analysis (COA) showed that different genotypes, as well as strains known to infect different cell types, are located at different places in the plane suggesting that CVB codon usage is reflecting an evolutionary process. The results of these studies suggest that CVB genomic biases are the result of co-evolution of translation adaptation to different cell environments and probably the need to escape anti-viral cell defenses.

Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1

Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years. In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically conserved. Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position. Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes. A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1. However the similarity was low for each virus and its host. These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes.

Characterization of Synonymous Codon Usage in the R1 Gene of Duck Enteritis Virus

In this paper, a corresponding analysis of the codon usage bias in the large subunit of ribonucleotide reductase (R1), encoded by UL39 gene from duck enteritis virus (DEV) CHv strain (Assigned Accession No.: EU071042) and 33 other reference herpesviruses was performed by using CAI, CHIPS and CUSP program of EMBOSS, aims to provide a basis for understanding the evolution and pathogenesis of DEV and for selecting appropriate host expression systems. The results showed that codon usage bias of DEV R1 gene strongly preferred to the synonymous with A and T at the third codon position; the phylogentic analysis revealed that DEV had a close evolutionary relationship with the avian Alphaherpesvirinae. In addition, the codon usage bias of DEV R1 gene was compared with those of E.coli, yeast and human. There are 17 codons showing distinct usage differences between DEV and E.coli, 13 codons between DEV and yeast, 20 codons between DEV and human. Therefore, the yeast expression system is more suitable for the target gene’s expression. The extent of codon usage bias in the DEV R1 gene was highly correlated with the gene expression level, therefore the results may provide useful information for the study of classification and function of the target gene.

Analysis of Synonymous Codon Usage Bias in D15 Gene Encoded Surface Antigen of Riemerella Anatipestifer

In order to provide a basis for understanding the evolutionary relationship and pathogenesis of Riemerella anatipestifer and selecting a appropriate host expression systems to improve the expression of target gene in vivo and in vitro, we identified the codon bias in the newly confirmed D15 gene of Riemerella anatipestifer ATCC 11845 strain and performed comparative analysis of the codon usage bias between D15 gene in R. anatipestifer and the other 10 referenced Flavobacteriaceaes by a series of online bioinformatics softwares. The results revealed that the synonymous codons with A and T at the third codon position had widely usage in the codon of D15 gene of R. anatipestifer. In addition, there were 70 rare codons in the ORF of the D15 of R. anatipestifer, and 32 codons showing distinct usage differences between R. anatipestifer and E. coli, 30 codons between R. anatipestifer and Homo sapiens, 16 codons between R. anatipestifer and yeast, indicated the yeast expression system may be more suitable for the expression of R. anatipestifer genes. The extent of codon usage bias in the D15 gene in R. anatipestifer was highly correlated with the gene expression level, therefore the results may provide useful information for gene classification and functional studies.

Analysis of Codon Usage and Nucleotide Compositional Traits of Morbilliviruses

In this study, the Relative Synonymous Codon Usage (RSCU) values, Effective Number of Codon (ENC) values, nucleotide contents and dinucleotide were used to consider codon usage pattern of each structure protein gene and genome among the members of Morbillivirus genus. The results showed that the overall extent of codon usage bias in Morbilliviruses is low (mean ENC = 54.84>35). The good correlation between the C+G) 12% and (G+C) 3% suggested that the mutational pressure rather than natural selection is the main factor that determines the codon usage bias and base component in Morbilliviruses. It is observed that synonymous codon usage pattern in Morbilliviruses can be divided into two groups. Under-represented CpG is a characteristic of all the members in Morbilliviruses. It may be a strategy to adapt to the host These analyses not only provided an insight into the variation of codon usage pattern among the genomes of Morbilliviruses but also were helpful in understanding the processes of the evolution of Morbilliviruses.

Codon usage bias: causative factors, quantification methods and genome‐wide patterns: with emphasis on insect genomes

Codon usage bias refers to the phenomenon where specific codons are used more often than other synonymous codons during translation of genes, the extent of which varies within and among species. Molecular evolutionary investigations suggest that codon bias is manifested as a result of balance between mutational and translational selection of such genes and that this phenomenon is widespread across species and may contribute to genome evolution in a significant manner. With the advent of whole-genome sequencing of numerous species, both prokaryotes and eukaryotes, genome-wide patterns of codon bias are emerging in different organisms. Various factors such as expression level, GC content, recombination rates, RNA stability, codon position, gene length and others (including environmental stress and population size) can influence codon usage bias within and among species. Moreover, there has been a continuous quest towards developing new concepts and tools to measure the extent of codon usage bias of genes. In this review, we outline the fundamental concepts of evolution of the genetic code, discuss various factors that may influence biased usage of synonymous codons and then outline different principles and methods of measurement of codon usage bias. Finally, we discuss selected studies performed using whole-genome sequences of different insect species to show how codon bias patterns vary within and among genomes. We conclude with generalized remarks on specific emerging aspects of codon bias studies and highlight the recent explosion of genome-sequencing efforts on arthropods (such as twelve Drosophila species, species of ants, honeybee, Nasonia and Anopheles mosquitoes as well as the recent launch of a genome-sequencing project involving 5000 insects and other arthropods) that may help us to understand better the evolution of codon bias and its biological significance.

Analysis of synonymous codon usage in hepatitis A virus.

BackgroundHepatitis A virus is the causative agent of type A viral hepatitis, which causes occasional acute hepatitis. Nevertheless, little information about synonymous codon usage pattern of HAV genome in the process of its evolution is available. In this study, the key genetic determinants of codon usage in HAV were examined.ResultsThe overall extent of codon usage bias in HAV is high in Picornaviridae. And the patterns of synonymous codon usage are quite different in HAV genomes from different location. The base composition is closely correlated with codon usage bias. Furthermore, the most important determinant that results in such a high codon bias in HAV is mutation pressure rather than natural selection.ConclusionsHAV presents a higher codon usage bias than other members of Picornaviridae. Compositional constraint is a significant element that influences the variation of synonymous codon usage in HAV genome. Besides, mutation pressure is supposed to be the major factor shaping the hyperendemic codon usage pattern of HAV.

Analysis of codon usage and nucleotide composition bias in polioviruses

BackgroundPoliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date.MethodsThe relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3.ResultsThe result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1.ConclusionThe information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.

A detailed comparative analysis on the overall codon usage patterns in Hepatitis A virus

Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae. HAV has several unique biological characteristics that distinguish it from other members of this family. Recent and previous studies revealed that codon usage plays a key role in HAV replication and evolution. In this study, the patterns of synonymous codon usage in HAV have been studied through multivariate statistical methods on 30 complete open reading frames (ORFs) from the available 30 full-length HAV sequences. Effective number of codons (ENC) indicates that the overall extent of codon usage bias in HAV genomes is significant. The relative dinucleotide abundances suggest that codon usage in HAV can also be strongly influenced by underlying biases in dinucleotide frequencies. These factors strongly correlated with the first major axis of correspondence analysis (COA) on relative synonymous codon usage (RSCU). The distribution of the HAV ORFs along the plane defined by the first two major axes in COA showed that different genotypes are located at different places in the plane, suggesting that HAV codon usage is also reflecting an evolutionary process. It has been very recently described that fine-tuning translation kinetics selection also contributes to codon usage bias of HAV. The results of these studies suggest that HAV genomic biases are the result of the co-evolution of genome composition, controlled translation kinetics and probably the ability to escape the antiviral cell responses.