厌氧性粘菌基因组中密码对的使用

分析了厌氧性粘菌(Anaeromyxobacter_dehalogenans_2N-C)基因组中密码对的使用,发现其全基因组中有5.2%的密码对模式是缺失的.分析结果表明其密码对的偏好至少可能是四个方面压力的结果:(1)基因组局部的及整体的GC含量,(2)密码对中二核苷酸的组分,(3)氨基酸的亲疏水性,(4)基因组中二肽的保守水平。     

Synonymous codon usage pattern among the S,M, and L segments in Crimean-congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever (CCHF) virus is one among the major zoonosis viral diseases that use the Hyalomma ticks as their transmission vector to cause viral infection to the human and mammalian community. The fatality of infectious is high across the world especially in Africa, Asia, Middle East, and Europe. This study regarding codon usage bias of S, M, and L segments of the CCHF virus pertaining to the host Homo sapiens, reveals in-depth information about the evolutionary characteristics of CCHFV. Relative Synonymous Codon Usage (RSCU), Effective number of codons (ENC) were calculated, to determine the codon usage pattern in each segment. Correlation analysis between Codon adaptation index (CAI), GRAVY (Hydrophobicity), AROMO (Aromaticity), and nucleotide composition revealed bias in the codon usage pattern. There was no strong codon bias found among any segments of the CCHF virus, indicating both the factors i.e., natural selection and mutational pressure shapes the codon usage bias.     

基于密码对使用的基因组进化

以密码对使用偏好性和密码对中二核苷酸频率分别构建了系统发育树。发现用40种模式生物编码序列中密码对的二核苷酸频率构建的系统发育树,明显将生物按进化分成细菌,古菌,真核生物;用密码对使用偏好性指标构建的系统发育树与基于密码对中二核苷酸频率的系统发育树基本一致。结果表明密码对中二核苷酸组分是密码对偏好的决定因素之一。     

ACUA: a software tool for automated codon usage analysis

Currently available codon usage analysis tools lack intuitive graphical user interface and are limited to inbuilt calculations. ACUA (Automated Codon Usage Tool) has been developed to perform high throughput sequence analysis aiding statistical profiling of codon usage. The results of ACUA are presented in a spreadsheet with all perquisite codon usage data required for statistical analysis, displayed in a graphical interface. The package is also capable of on-click sequence retrieval from the results interface, and this feature is unique to ACUA. AVAILABILITY: The package is available for non-commercial purposes and can be downloaded from: http://www.bioinsilico.com/acua.     

Comparative Genomics of Trypanosomatid Pathogens using Codon Usage Bias

It is well known that an amino acid can be encoded by more than one codon, called synonymous codons. The preferential use of one particular codon for coding an amino acid is referred to as codon usage bias (CUB). A quantitative analytical method, CUB and a related tool, Codon Adaptative Index have been applied to comparatively study whole genomes of a few pathogenic Trypanosomatid species. This quantitative attempt is of direct help in the comparison of qualitative features like mutational and translational selection. Pathogens of the Leishmania and Trypanosoma genus cause debilitating disease and suffering in human beings and animals. Of these, whole genome sequences are available for only five species. The complete coding sequences (CDS), highly expressed, essential and low expressed genes have all been studied for their CUB signature. The codon usage bias of essential genes and highly expressed genes show distribution similar to codon usage bias of all CDSs in Trypanosomatids. Translational selection is the dominant force selecting the preferred codon, and selection due to mutation is negligible. In contrast to an earlier study done on these pathogens, it is found in this work that CUB and CAI may be used to distinguish the Trypanosomatid genomes at the sub-genus level. Further, CUB may effectively be used as a signature of the species differentiation by using Principal Component Analysis (PCA).

Abbreviations

CUB - Codon Usage Bias, CAI - Codon Adaptative Index, CDS - Coding sequences, t-RNA - Transfer RNA, PCA - Principal Component Analysis.     

Analysis of synonymous codon usage in 11 human bocavirus isolates

Human Bocavirus (HBoV) is a novel virus which can cause respiratory tract disease in infants or children. In this study, the codon usage bias and the base composition variations in the available 11 complete HBoV genome sequences have been investigated. Although, there is a significant variation in codon usage bias among different HBoV genes, codon usage bias in HBoV is a little slight, which is mainly determined by the base compositions on the third codon position and the effective number of codons (ENC) value. The results of correspondence analysis (COA) and Spearman's rank correlation analysis reveals that the G + C compositional constraint is the main factor that determines the codon usage bias in HBoV and the gene's function also contributes to the codon usage in this virus. Moreover, it was found that the hydrophobicity of each protein and the gene length are also critical in affecting these viruses’ codon usage, although they were less important than that of the mutational bias and the genes’ function. At last, the relative synonymous codon usage (RSCU) of 44 genes from these 11 HBoV isolates is analyzed using a hierarchical cluster method. The result suggests that genes with same function yet from different isolates are classified into the same lineage and it does not depend on geographical location. These conclusions not only can offer an insight into the codon usage patterns and gene classification of HBoV, but also may help in increasing the efficiency of gene delivery/expression systems.     

In Arabidopsis thaliana codon volatility scores reflect GC3 composition rather than selective pressure

ABSTRACT: BACKGROUND: Synonymous codon usage bias has typically been correlated with, and attributed to translational efficiency. However, there are other pressures on genomic sequence composition that can affect codon usage patterns such as mutational biases. This study provides an analysis of the codon usage patterns in Arabidopsis thaliana in relation to gene expression levels, codon volatility, mutational biases and selective pressures. RESULTS: We have performed synonymous codon usage and codon volatility analyses for all genes in the A. thaliana genome. In contrast to reports for species from other kingdoms, we find that neither codon usage nor volatility are correlated with selection pressure (as measured by dN/dS), nor with gene expression levels on a genome wide level. Our results show that codon volatility and usage are not synonymous, rather that they are correlated with the abundance of G and C at the third codon position (GC3). CONCLUSIONS: Our results indicate that while the A. thaliana genome shows evidence for synonymous codon usage bias, this is not related to the expression levels of its constituent genes. Neither codon volatility nor codon usage are correlated with expression levels or selective pressures but, because they are directly related to the composition of G and C at the third codon position, they are the result of mutational bias. Therefore, in A. thaliana codon volatility and usage do not result from selection for translation efficiency or protein functional shift as measured by positive selection.     

The Nonrandom Location of Synonymous Codons Suggests That Reading Frame-Independent Forces Have Patterned Codon Preferences

Biased codon usage is common in eukaryotic and prokaryotic genes. Evidence from Escherichia, Saccharomyces, and Drosophila indicates that it favors translational efficiency and accuracy. However, to date no functional advantages have been identified in the codon–anticodon interactions involving the most frequently used (preferred) codons. Here we present evidence that forces not related to the individual codon–anticodon interaction may be involved in determining which synonymous codons are preferred or avoided. We show that the ``off-frame' trinucleotide motif preferences inferrable from Drosophila coding regions are often in the same direction as Drosophila's ``in-frame' codon preferences, i.e., its codon usage. The off-frame preferences were inferred from the nonrandomness of the location of confamilial synonymous codons along coding regions—a pattern often described as a context dependence of nucleotide choice at synonymous positions or as codon-pair bias. We relied on randomizations of the location of confamilial codons that do not alter, and cannot be influenced by, the encoded amino acid sequences, codon usage, or base composition of the genes examined. The statistically significant congruency of in-frame and off-frame trinucleotide preferences suggests that the same kind of reading-frame-independent force(s) may also influence synonymous codon choice. These forces may have produced biases in codon usage that then led to the evolution of the translational advantages of these motifs as preferred codons. Under this scenario, tRNA pool size differences between preferred and nonpreferred codons initially were evolved to track the default overrepresentation of codons with preferred motifs. The motif preference hypothesis can explain the structuring of codon preferences and the similarities in the codon usages of distantly related organisms. Received: 10 November 1998 / Accepted: 23 February 1999     

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.     

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.     

Codon usage divergence of homologous vertebrate genes and codon usage clock

Summary This paper is concerned with the divergence of synonymous codon usage and its bias in three homologous genes within vertebrate species. Genetic distances among species are described in terms of synonymous codon usage divergence and the correlation is found between the genetic distances and taxonomic distances among species under study. A codon usage clock is reported in alphaglobin and beta-globin. A method is developed to define the synonymous codon preference bias and it is observed that the bias changes considerably among species.     

Studies on codon usage in Entamoeba histolytica

Codon usage bias of Entamoeba histolytica, a protozoan parasite, was investigated using the available DNA sequence data. Entamoeba histolytica having AT rich genome, is expected to have A and/or T at the third position of codons. Overall codon usage data analysis indicates that A and/or T ending codons are strongly biased in the coding region of this organism. However, multivariate statistical analysis suggests that there is a single major trend in codon usage variation among the genes. The genes which are supposed to be highly expressed are clustered at one end, while the majority of the putatively lowly expressed genes are clustered at the other end. The codon usage pattern is distinctly different in these two sets of genes. C ending codons are significantly higher in the putatively highly expressed genes suggesting that C ending codons are translationally optimal in this organism. In the putatively lowly expressed genes A and/or T ending codons are predominant, which suggests that compositional constraints are playing the major role in shaping codon usage variation among the lowly expressed genes. These results suggest that both mutational bias and translational selection are operational in the codon usage variation in this organism.     

Compositional correlation and codon usage studies in Buchnera aphidicola

Compositional distributions in three different codon positions as well as codon usage biases of all available DNA sequences of Buchnera aphidicola genome have been analyzed. It was observed that GC levels among the three codon positions is I>II>III as observed in other extremely high AT rich organisms. B. aphidicola being an AT rich organism is expected to have A and/or T at the third positions of codons. Overall codon usage analyses indicate that A and/or T ending codons are predominant in this organism and some particular amino acids are abundant in the coding region of genes. However, multivariate statistical analysis indicates two major trends in the codon usage variation among the genes; one being strongly correlated with the GC contents at the third synonymous positions of codons, and the other being associated with the expression level of genes. Moreover, codon usage biases of the highly expressed genes are almost identical with the overall codon usage biases of all the genes of this organism. These observations suggest that mutational bias is the main factor in determining the codon usage variation among the genes in B. aphidicola.     

Multiscale Modeling of Metabolism and Macromolecular Synthesis in E. coli and Its Application to the Evolution of Codon Usage

Biological systems are inherently hierarchal and multiscale in time and space. A major challenge of systems biology is to describe biological systems as a computational model, which can be used to derive novel hypothesis and drive experiments leading to new knowledge. The constraint-based reconstruction and analysis approach has been successfully applied to metabolism and to the macromolecular synthesis machinery assembly. Here, we present the first integrated stoichiometric multiscale model of metabolism and macromolecular synthesis for Escherichia coli K12 MG1655, which describes the sequence-specific synthesis and function of almost 2000 gene products at molecular detail. We added linear constraints, which couple enzyme synthesis and catalysis reactions. Comparison with experimental data showed improvement of growth phenotype prediction with the multiscale model over E. coli’s metabolic model alone. Many of the genes covered by this integrated model are well conserved across enterobacters and other, less related bacteria. We addressed the question of whether the bias in synonymous codon usage could affect the growth phenotype and environmental niches that an organism can occupy. We created two classes of in silico strains, one with more biased codon usage and one with more equilibrated codon usage than the wildtype. The reduced growth phenotype in biased strains was caused by tRNA supply shortage, indicating that expansion of tRNA gene content or tRNA codon recognition allow E. coli to respond to changes in codon usage bias. Our analysis suggests that in order to maximize growth and to adapt to new environmental niches, codon usage and tRNA content must co-evolve. These results provide further evidence for the mutation-selection-drift balance theory of codon usage bias. This integrated multiscale reconstruction successfully demonstrates that the constraint-based modeling approach is well suited to whole-cell modeling endeavors.     

Interaction of silent and replacement changes in eukaryotic coding sequences

Summary We examined the codon usages in wellconserved and less-well-conserved regions of vertebrate protein genes and found them to be similar. Despite this similarity, there is a statistically significant decrease in codon bias in the less-well-conserved regions. Our analysis suggests that although those codon changes initially fixed under amino acid replacements tend to follow the overall codon usage pattern, they also reduce the bias in codon usage. This decrease in codon bias leads one to predict that the rate of change of synonymous codons should be greater in those regions that are less well conserved at the amino acid level than in the better-conserved regions. Our analysis supports this prediction. Furthermore, we demonstrate a significantly elevated rate of change of synonymous codons among the adjacent codons 5 to amino acid replacement positions. This provides further support for the idea that there are contextual constraints on the choice of synonymous codons in eukaryotes.     

Mutational Bias and Gene Expression Level Shape Codon Usage in Thermobifida fusca YX

In this study major factors shaping codon and amino acid usage variation in Thermobifida fusca YX are reported. It is a major degrader of plant cell walls. It produces spores that can be allergenic and has been associated with a condition called farmers lung. For comparison, two other closely related Actinobacteria, S. coelicolor and N. farcinica were considered. Correspondence analysis on RSCU (Relative Synonymous Codon Usage) showed significant correlation between the major trend of codon usage variation and gene expression level assessed by the "Codon Adaptation Index" (CAI) values. The result was further confirmed from distribution of genes along the first axis. In addition, N_{c} (effective number of codons) plot, SCUO (synonymous codon usage order) plot and correlation analyses showed that base composition and mutational bias have a dominant role in codon usage variation. Furthermore, gene expression level, hydrophobicity and aromaticity have played a significant role in the source of variations for amino acid usage. In addition, codon preference for genes at higher expression level was found to be similar among three different genera. Notably, 14 codons optimally used by Thermobifida fusca YX and its comparative study with S. coelicolor and N. farcinica might provide some useful information for their further study of molecular evolution and genetic engineering.     

沙枣叶绿体全基因组序列及其使用密码子偏性分析

该研究以2株野生沙枣(Elaeagnus angustifolia Linn.)嫩枝经温室水培后的嫩叶为材料,采用CTAB法分别提取总DNA,并利用第二代测序技术进行总DNA从头测序,组装后得到2株沙枣叶绿体基因组全序列,并详细分析了其蛋白质编码基因密码子使用的偏好性及其原因,为沙枣叶绿体基因工程和分子系统进化等研究奠定基础。结果显示:(1)组装得到沙枣叶绿体基因组序列全长150 546 bp,由长度为81 113 bp的长单拷贝(LSC)区域和25 494 bp的短单拷贝(SSC)区域,以及1对分隔开它们的长18 445 bp的反向重复序列(IRS)组成;注释共得到132个基因,包括86个蛋白编码基因、38个tRNA基因和8个rRNA基因。(2)沙枣叶绿体基因组蛋白编码基因密码子的第三位碱基GC含量(GC_3)为28.47%,明显低于整个叶绿体基因组GC含量(37%),也低于第一位(GC_1)和第二位(GC_2)碱基的GC含量,说明密码子对AT碱基结尾有偏好性;其中, UCU、CCU、UGU、GCU、CUU、GAU、UCA和UAA为最优密码子。(3)同义密码子相对使用频率(RSCU)分析发现,影响密码子使用模式的因素并不单一,密码子的偏好性受到突变、选择及其他因素的共同影响,并且自然选择表达引起的序列差异比突变对密码子偏好性的影响要显著;中性绘图分析、有效密码子数(ENC-plot)分析和奇偶偏好性(PR2-plot)分析表明,沙枣叶绿体基因组使用密码子的偏性受选择的影响更大。(4)通过最大似然法、最大简约法和贝叶斯方法对胡颓子科6个物种和1个枣的叶绿体基因序列构建系统发育树,与它们使用密码子偏性聚类的结果一致,表明叶绿体基因组使用密码子偏性与物种的亲缘关系相关。