Transfer RNA Gene Numbers may not be Completely Responsible for the Codon Usage Bias in Asparagine, Isoleucine, Phenylalanine, and Tyrosine in the High Expression Genes in Bacteria

It is generally believed that the effect of translational selection on codon usage bias is related to the number of transfer RNA genes in bacteria, which is more with respect to the high expression genes than the whole genome. Keeping this in the background, we analyzed codon usage bias with respect to asparagine, isoleucine, phenylalanine, and tyrosine amino acids. Analysis was done in seventeen bacteria with the available gene expression data and information about the tRNA gene number. In most of the bacteria, it was observed that codon usage bias and tRNA gene number were not in agreement, which was unexpected. We extended the study further to 199 bacteria, limiting to the codon usage bias in the two highly expressed genes rpoB and rpoC which encode the RNA polymerase subunits β and β′, respectively. In concordance with the result in the high expression genes, codon usage bias in rpoB and rpoC genes was also found to not be in agreement with tRNA gene number in many of these bacteria. Our study indicates that tRNA gene numbers may not be the sole determining factor for translational selection of codon usage bias in bacterial genomes.     

Unusual codon usage bias in low expression genes of Vibrio cholerae

Positive correlation between gene expression and synonymous codon usage bias is well documented in the literature. However, in the present study of Vibrio cholerae genome, we have identified a group of genes having unusually high codon usage bias despite being low potential expressivity. Our results suggest that codon usage in lowly expressed genes might also be selected on to preferably use non-optimal codons to maintain a low cellular concentration of the proteins that they encode. This would predict that lowly expressed genes are also biased in codon usage, but in a way that is opposite to the bias of highly expressed genes.     

Impact of translational selection on codon usage bias in the archaeon Methanococcus maripaludis

Patterns of codon usage have been extensively studied among Bacteria and Eukaryotes, but there has been little investigation of species from the third domain of life, the Archaea. Here, we examine the nature of codon usage bias in a methanogenic archaeon, Methanococcus maripaludis. Genome-wide patterns of codon usage are dominated by a strong A + T bias, presumably largely reflecting mutation patterns. Nevertheless, there is variation among genes in the use of a subset of putatively translationally optimal codons, which is strongly correlated with gene expression level. In comparison with Bacteria such as Escherichia coli, the strength of selected codon usage bias in highly expressed genes in M. maripaludis seems surprisingly high given its moderate growth rate. However, the pattern of selected codon usage differs between M. maripaludis and E. coli: in the archaeon, strongly selected codon usage bias is largely restricted to twofold degenerate amino acids (AAs). Weaker bias among the codons for fourfold degenerate AAs is consistent with the small number of tRNA genes in the M. maripaludis genome.     

Codon usage and gene expression pattern of Stenotrophomonas maltophilia R551-3 for pathogenic mode of living

Stenotrophomonas maltophilia strain R551-3 is a multiple-antibiotic-resistant opportunistic human pathogen involved in nosocomial infections. It has a widely distributed GC-rich (>66%) genome. Analysis of differential expression of the genes of this genome reveals that majority of genes belonging to highly expressed category are mostly present on lagging strand without showing any strand specific codon usage bias. Relatively small number of lowly expressed genes is equally distributed on both leading and lagging strands with a difference in codon usage pattern between them. Among several multi drug resistance genes of S. maltophilia involving lowly expressed category some are predicted as horizontally transferred. It can be inferred that horizontally transferred genes may have been imported into this genome for their pathogenic mode of living. Our study may help to modify the expression level of the target genes of this human pathogen in order to control its infection.     

Regularities of context-dependent codon bias in eukaryotic genes

Nucleotides surrounding a codon influence the choice of this particular codon from among the group of possible synonymous codons. The strongest influence on codon usage arises from the nucleotide immediately following the codon and is known as the N₁ context. We studied the relative abundance of codons with N₁ contexts in genes from four eukaryotes for which the entire genomes have been sequenced: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. For all the studied organisms it was found that 90% of the codons have a statistically significant N₁ context-dependent codon bias. The relative abundance of each codon with an N₁ context was compared with the relative abundance of the same 4mer oligonucleotide in the whole genome. This comparison showed that in about half of all cases the context-dependent codon bias could not be explained by the sequence composition of the genome. Ranking statistics were applied to compare context-dependent codon biases for codons from different synonymous groups. We found regularities in N₁ context-dependent codon bias with respect to the codon nucleotide composition. Codons with the same nucleotides in the second and third positions and the same N₁ context have a statistically significant correlation of their relative abundances.     

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

Mycoplasma bovis is a major pathogen causing arthritis, respiratory disease and mastitis in cattle. A better understanding of its genetic features and evolution might represent evidences of surviving host environments. In this study, multiple factors influencing synonymous codon usage patterns in M. bovis (three strains’ genomes) were analyzed. The overall nucleotide content of genes in the M. bovis genome is AT-rich. Although the G and C contents at the third codon position of genes in the leading strand differ from those in the lagging strand (p<0.05), the 59 synonymous codon usage patterns of genes in the leading strand are highly similar to those in the lagging strand. The over-represented codons and the under-represented codons were identified. A comparison of the synonymous codon usage pattern of M. bovis and cattle (susceptible host) indicated the independent formation of synonymous codon usage of M. bovis. Principal component analysis revealed that (i) strand-specific mutational bias fails to affect the synonymous codon usage pattern in the leading and lagging strands, (ii) mutation pressure from nucleotide content plays a role in shaping the overall codon usage, and (iii) the major trend of synonymous codon usage has a significant correlation with the gene expression level that is estimated by the codon adaptation index. The plot of the effective number of codons against the G+C content at the third codon position also reveals that mutation pressure undoubtedly contributes to the synonymous codon usage pattern of M. bovis. Additionally, the formation of the overall codon usage is determined by certain evolutionary selections for gene function classification (30S protein, 50S protein, transposase, membrane protein, and lipoprotein) and translation elongation region of genes in M. bovis. The information could be helpful in further investigations of evolutionary mechanisms of the Mycoplasma family and heterologous expression of its functionally important proteins.     

Characterization of synonymous codon usage bias in the pseudorabies virus US1 gene

In the present study, we examined the codon usage bias between pseudorabies virus (PRV) US1 gene and the US1-like genes of 20 reference alphaherpesviruses. Comparative analysis showed noticeable disparities of the synonymous codon usage bias in the 21 alphaherpesviruses, indicated by codon adaptation index, effective number of codons (ENc) and GC3s value. The codon usage pattern of PRV US1 gene was phylogenetically conserved and similar to that of the US1-like genes of the genus Varicellovirus of alphaherpesvirus, with a strong bias towards the codons with C and G at the third codon position. Cluster analysis of codon usage pattern of PRV US1 gene with its reference alphaherpesviruses demonstrated that the codon usage bias of US1-like genes of 21 alphaherpesviruses had a very close relation with their gene functions. ENc-plot revealed that the genetic heterogeneity in PRV US1 gene and the 20 reference alphaherpesviruses was constrained by G+C content, as well as the gene length. In addition, comparison of codon preferences in the US1 gene of PRV with those of E. coli, yeast and human revealed that there were 50 codons showing distinct usage differences between PRV and yeast, 49 between PRV and human, but 48 between PRV and E. coli. Although there were slightly fewer differences in codon usages between E.coli and PRV, the difference is unlikely to be statistically significant, and experimental studies are necessary to establish the most suitable expression system for PRV US1. In conclusion, these results may improve our understanding of the evolution, pathogenesis and functional studies of PRV, as well as contributing to the area of herpesvirus research or even studies with other viruses.     

Analysis of the Codon Usage Pattern in the Vibrio Cholerae Genome

Abstract

The codon usage in the Vibrio cholerae genome is analyzed in this paper. Although there are much more genes on the chromosome 1 than on chromosome 2, the codon usage patterns of genes on the two chromosomes are quite similar, indicating that the two chromosomes may have coexisted in the same cell for a very long history. Unlike the base frequency pattern observed in other genomes, the G+C content at the third codon position of the V. cholerae genome varies in a rather small interval. The most notable feature of codon usage of V. cholerae genome is that there is a fraction of genes show significant bias in base choice at the second codon position. The 2006 known genes can be classified into two clusters according to the base frequencies at this position. The smaller cluster contains 227 genes, most of which code for proteins involved in transport and binding functions. The encoding products of these genes have significant bias in amino acids composition as compared with other genes. The codon usage patterns for the 1836 function unknown ORFs are also analyzed, which is useful to study their functions.     

Analysis of genomic characters reveals that four distinct gene clusters are correlated with different functions in Burkholderia cenocepacia AU 1054

Possessing three circular chromosomes is a distinct genomic characteristic of Burkholderia cenocepacia AU 1054, a clinically important pathogen in cystic fibrosis. In this study, base composition, codon usage and functional role category were analyzed in the B. cenocepacia AU 1054 genome. Although no bias in the base and codon usage was detected between any two chromosomes, function differences did exist in the genes of each chromosome. Similar base composition and differential functional role categories indicated that genes on these three chromosomes were relatively stable and that a proper division of labor was established. Based on variations in the base or codon usage, four small gene clusters were observed in all of the genes. Multivariate analysis revealed that protein hydrophobicity played a predominant role in shaping base usage bias, while horizontal gene transfer and the gene expression level were the two most important factors that affected the codon usage bias. Interestingly, we also found that these gene clusters were correlated with different biological functions: (i) 45 pyrimidine-leading-codon preferred genes were predominantly involved in regulatory function; (ii) most drug resistance-related genes involved in 826 genes that coding for hydrophobic proteins; (iii) most of the 111 horizontal transfer genes were responsible for genomic plasticity; and (iv) 73 highly expressed genes (predicted by their codon adaptation index values) showed environmental adaptation to cystic fibrosis. Our results showed that genes with base or codon usage bias were affected by mutational pressure and natural selection, and their functions could contribute to drug assistance and transmissible activity in B. cenocepacia.     

Evidence from simulation studies for selective constraints on the codon usage of the Angiosperm psbA gene

The codon usage of the Angiosperm psbA gene is atypical for flowering plant chloroplast genes but similar to the codon usage observed in highly expressed plastid genes from some other Plantae, particularly Chlorobionta, lineages. The pattern of codon bias in these genes is suggestive of selection for a set of translationally optimal codons but the degree of bias towards these optimal codons is much weaker in the flowering plant psbA gene than in high expression plastid genes from lineages such as certain green algal groups. Two scenarios have been proposed to explain these observations. One is that the flowering plant psbA gene is currently under weak selective constraints for translation efficiency, the other is that there are no current selective constraints and we are observing the remnants of an ancestral codon adaptation that is decaying under mutational pressure. We test these two models using simulations studies that incorporate the context-dependent mutational properties of plant chloroplast DNA. We first reconstruct ancestral sequences and then simulate their evolution in the absence of selection on codon usage by using mutation dynamics estimated from intergenic regions. The results show that psbA has a significantly higher level of codon adaptation than expected while other chloroplast genes are within the range predicted by the simulations. These results suggest that there have been selective constraints on the codon usage of the flowering plant psbA gene during Angiosperm evolution.     

Codon usage <Emphasis Type="BoldItalic">vis-a-vis</Emphasis> start and stop codon context analysis of three dicot species

To understand the variation in genomic composition and its effect on codon usage, we performed the comparative analysis of codon usage and nucleotide usage in the genes of three dicots, Glycine max, Arabidopsis thaliana and Medicago truncatula. The dicot genes were found to be A/T rich and have predominantly A-ending and/or T-ending codons. GC3s directly mimic the usage pattern of global GC content. Relative synonymous codon usage analysis suggests that the high usage frequency of A/T over G/C mononucleotide containing codons in AT-rich dicot genome is due to compositional constraint as a factor of codon usage bias. Odds ratio analysis identified the dinucleotides TpG, TpC, GpA, CpA and CpT as over-represented, where, CpG and TpA as under-represented dinucleotides. The results of (NcExp?NcObs)/NcExp plot suggests that selection pressure other than mutation played a significant role in influencing the pattern of codon usage in these dicots. PR2 analysis revealed the significant role of selection pressure on codon usage. Analysis of varience on codon usage at start and stop site showed variation in codon selection in these sites. This study provides evidence that the dicot genes were subjected to compositional selection pressure.     

Perturbation of Parentally Biased Gene Expression during Interspecific Hybridization

Interspecific hybridization often induces epigenetic remodeling that leads to transposon activation, gene expression changes, and loss of imprinting. These genomic changes can be deleterious and contribute to postzygotic hybrid incompatibility. In Arabidopsis, loss of genomic imprinting of PHERES1 and presumed failure of Polycomb Repressive Complex contributes to seed inviability observed in A. thaliana X A. arenosa interspecific hybrids. We used this species pair to further analyze the relationship between parentally biased gene expression and postzygotic hybrid incompatibility using two A. thaliana accessions, Col-0 and C24, with differential seed survival. We found that parentally biased expression was perturbed to a similar degree in both A. thaliana hybrids for PHERES1, HDG3, and six other normally paternally expressed genes. We propose that early genome remodeling and loss of imprinting of seed development genes induces lethality in both compatible and incompatible hybrids.     

Codon usage bias and base composition in MHC genes in humans and common chimpanzees

 Codon bias and base composition in major histocompatibility complex (MHC) sequences have been studied for both class I and II loci in Homo sapiens and Pan troglodytes. There is low to moderate codon bias for the MHC of humans and chimpanzees. In the class I loci, the same level of moderate codon bias is seen for HLA-B, HLA-C, Patr-A, Patr-B, and Patr-C, while at HLA-A the level of codon bias is lower. There is a correlation between codon usage bias and G+C content in the A and B loci in humans and chimps, but not at the C locus. To examine the effect of diversifying selection on codon bias, we subdivided class I alleles into antigen recognition site (ARS) and non-ARS codons. ARS codons had lower bias than non-ARS codons. This may indicate that the constraint of codon bias on nucleotide substitution may be selected against in ARS codons. At the class II loci, there are distinct differences between alpha and beta chain genes with respect to codon usage, with the beta chain genes being much more biased. Species-specific differences in base composition were seen in exon 2 at the DRB1 locus, with lower GC content in chimpanzees. Considering the complex evolutionary history of MHC genes, the study of codon usage patterns provides us with a better understanding of both the evolutionary history of these genes and the evolution of synonymous codon usage in genes under natural selection. Received: 2 April 1998 / Revised: 2 September 1998     

Comparison of Correspondence Analysis Methods for Synonymous Codon Usage in Bacteria

Synonymous codon usage varies both between organisms and among genes within a genome, and arises due to differences in G + C content, replication strand skew, or gene expression levels. Correspondence analysis (CA) is widely used to identify major sources of variation in synonymous codon usage among genes and provides a way to identify horizontally transferred or highly expressed genes. Four methods of CA have been developed based on three kinds of input data: absolute codon frequency, relative codon frequency, and relative synonymous codon usage (RSCU) as well as within-group CA (WCA). Although different CA methods have been used in the past, no comprehensive comparative study has been performed to evaluate their effectiveness. Here, the four CA methods were evaluated by applying them to 241 bacterial genome sequences. The results indicate that WCA is more effective than the other three methods in generating axes that reflect variations in synonymous codon usage. Furthermore, WCA reveals sources that were previously unnoticed in some genomes; e.g. synonymous codon usage related to replication strand skew was detected in Rickettsia prowazekii. Though CA based on RSCU is widely used, our evaluation indicates that this method does not perform as well as WCA.Key words: correspondence analysis, synonymous codon usage, horizontal gene transfer, strand-specific mutational bias, translational selection     

Selection shapes the patterns of codon usage in three closely related species of genus Misgurnus

Neutrality plots revealed that selection probably dominates codon bias, whereas mutation plays only a minor role, in shaping the codon bias in three loaches, Misgurnus anguillicaudatus, M. mohoity, and M. bipartitus. These three species also clearly showed similar tendencies in the preferential usage of codons. Nineteen, nine, and 14 preferred codon pairs and 179, 182, and 173 avoided codon pairs were also detected in M. anguillicaudatus, M. bipartitus, and M. mohoity, respectively, and the most frequently avoided type of cP3-cA1 dinucleotide in these species was nnUAnn. The expression-linked patterns of codon usage revealed that higher expression was associated with higher GC₃, lower ENC, and a smaller proportion of amino acids with high size/complexity (S/C) scores in these three species. These results elucidate selectively driven codon bias in Misgurnus species, and reveal the potential importance of expression-mediated selection in shaping the genome evolution of fish.     

杜仲基因密码子使用模式分析

为了解杜仲基因密码子使用模式,该文以杜仲基因组密码子为研究对象,运用CodonW软件对杜仲的320个蛋白编码基因进行同义密码子相对使用频率(RSCU)分析、ENC-GC3s关联分析编码基因的密码子ENC值、PR2-plot偏倚分析编码基因的密码子碱基使用频率,并运用CUSP软件与Codon Usage Database...