Site-specific codon bias in bacteria.
Ontology highlight
ABSTRACT:
SUBMITTER: Smith JM
PROVIDER: S-EPMC1207003 | biostudies-other | 1996 Mar
REPOSITORIES: biostudies-other
Publications
Sequences of the gapA and ompA genes from 10 genera of enterobacteria have been analyzed. There is strong bias in codon usage, but different synonymous codons are preferred at different sites in the same gene. Site-specific preference for unfavored codons is not confined to the first 100 codons and is usually manifest between two codons utilizing the same tRNA. Statistical analyses, based on conclusions reached in an accompanying paper, show that the use of an unfavored codon at a given site in ...[more]
Similar Datasets
Project description:Among bacteria, many species have synonymous codon usage patterns that have been influenced by natural selection for those codons that are translated more accurately and/or efficiently. However, in other species selection appears to have been ineffective. Here, we introduce a population genetics-based model for quantifying the extent to which selection has been effective. The approach is applied to 80 phylogenetically diverse bacterial species for which whole genome sequences are available. The strength of selected codon usage bias, S, is found to vary substantially among species; in 30% of the genomes examined, there was no significant evidence that selection had been effective. Values of S are highly positively correlated with both the number of rRNA operons and the number of tRNA genes. These results are consistent with the hypothesis that species exposed to selection for rapid growth have more rRNA operons, more tRNA genes and more strongly selected codon usage bias. For example, Clostridium perfringens, the species with the highest value of S, can have a generation time as short as 7 min.
| S-EPMC549432 | biostudies-literature
Project description:Codon usage bias is the preferential or non-random use of synonymous codons, a ubiquitous phenomenon observed in bacteria, plants and animals. Different species have consistent and characteristic codon biases. Codon bias varies not only with species, family or group within kingdom, but also between the genes within an organism. Codon usage bias has evolved through mutation, natural selection, and genetic drift in various organisms. Genome composition, GC content, expression level and length of genes, position and context of codons in the genes, recombination rates, mRNA folding, and tRNA abundance and interactions are some factors influencing codon bias. The factors shaping codon bias may also be involved in evolution of the universal genetic code. Codon-usage bias is critical factor determining gene expression and cellular function by influencing diverse processes such as RNA processing, protein translation and protein folding. Codon usage bias reflects the origin, mutation patterns and evolution of the species or genes. Investigations of codon bias patterns in genomes can reveal phylogenetic relationships between organisms, horizontal gene transfers, molecular evolution of genes and identify selective forces that drive their evolution. Most important application of codon bias analysis is in the design of transgenes, to increase gene expression levels through codon optimization, for development of transgenic crops. The review gives an overview of deviations of genetic code, factors influencing codon usage or bias, codon usage bias of nuclear and organellar genes, computational methods to determine codon usage and the significance as well as applications of codon usage analysis in biological research, with emphasis on plants.
| S-EPMC8613526 | biostudies-literature
Project description:Human papillomavirus type 16 (HPV16) is the most prevalent HPV type causing cervical cancers. Herein, using 1597 full genomes, we systemically investigated the mutation profiles, surface protein glycosylation sites and the codon usage bias (CUB) of HPV16 from different lineages and sublineages. Multiple lineage- or sublineage-conserved mutation sites were identified. Glycosylation analysis showed that HPV16 lineage D contained the highest number of different glycosylation sites from lineage A in both L1 and L2 capsid proteins, which might lead to their antigenic distances between the two lineages. CUB analysis showed that the HPV16 open reading frames (ORFs) preferred codons ending with A/T. The CUB of HPV16 ORFs was mainly affected by natural selection except for E1, E5 and L2. HPV16 only shared some of the preferred codons with humans, which might help reduce competition in translational resources. These findings increase our understanding of the heterogeneity between HPV16 lineages and sublineages, and the adaptation mechanism of HPV in human cells. In summary, this study might facilitate HPV classification and improve vaccine development and application.
| S-EPMC8310365 | biostudies-literature
Project description:It is well known that in cancer gene families some members are more frequently mutated in tumor samples than their family counterparts. A paradigmatic case of this phenomenon is KRAS from the RAS family. Different explanations have been proposed ranging from differential interaction with other proteins to preferential expression or localization. Interestingly, it has been described that despite the high amino acid identity between RAS family members, KRAS employs an intriguing differential codon usage. Here, we found that this phenomenon is not exclusive to the RAS family. Indeed, in the RAS family and other oncogene families with two or three members, the most prevalently mutated gene in tumor samples employs a differential codon usage that is characteristic of genes involved in proliferation. Prompted by these observations, we chose the RAS family to experimentally demonstrate that the translation efficiency of oncogenes that are preferentially mutated in tumor samples is increased in proliferative cells compared to quiescent cells. These results were further validated by assessing the translation efficiency of KRAS in cell lines that differ in their tRNA expression profile. These differences are related to the cell division rate of the studied cells and thus suggest an important role in context-specific oncogene expression regulation. Altogether, our study demonstrates that dynamic translation programs contribute to shaping the expression profiles of oncogenes. Therefore, we propose this codon bias as a regulatory layer to control cell context-specific expression and explain the differential prevalence of mutations in certain members of oncogene families.
| S-EPMC7720162 | biostudies-literature
Project description:The access to information on the dynamic behaviour of large proteins is usually hindered as spectroscopic methods require the site-specific attachment of biophysical probes. A powerful emerging tool to tackle this issue is amber codon suppression. Till date, its application on large and complex multidomain proteins of MDa size has not been reported. Herein, we systematically investigate the feasibility to introduce different non-canonical amino acids into a 540 kDa homodimeric fatty acid synthase type I by genetic code expansion with subsequent fluorescent labelling. Our approach relies on a microplate-based reporter assay of low complexity using a GFP fusion protein to quickly screen for sufficient suppression conditions. Once identified, these findings were successfully utilized to upscale both the expression scale and the protein size to full-length constructs. These fluorescently labelled samples of fatty acid synthase were subjected to initial biophysical experiments, including HPLC analysis, activity assays and fluorescence spectroscopy. Successful introduction of such probes into a molecular machine such as fatty acid synthases may pave the way to understand the conformational variability, which is a primary intrinsic property required for efficient interplay of all catalytic functionalities, and to engineer them.
| S-EPMC6173736 | biostudies-literature
Project description:BackgroundSynonymous codons are used differentially in organisms from the three domains of life, a phenomenon referred to as codon usage bias. In addition, codon pair bias, particularly in the 3' codon context, has also been described in several organisms and is associated with the accuracy and rate of translation. An improved understanding of both types of bias is important for the optimization of heterologous protein expression, particularly in biotechnologically important organisms, such as the yeast Xanthophyllomyces dendrorhous, a promising bioresource for the carotenoid astaxanthin. Using genomic and transcriptomic data, the codon usage and codon context biases of X. dendrorhous open reading frames (ORFs) were analyzed to determine their expression levels, GC% and sequence lengths. X. dendrorhous totiviral ORFs were also included in these analyses.ResultsA total of 1,695 X. dendrorhous ORFs were identified through comparison with sequences in multiple databases, and the intron-exon structures of these sequences were determined. Although there were important expression variations among the ORFs under the studied conditions (different phases of growth and available carbon sources), most of these sequences were highly expressed under at least one of the analyzed conditions. Independent of the culture conditions, the highly expressed genes showed a strong bias in both codon usage and the 3' context, with a minor association with the GC% and no relationship to the sequence length. The codon usage and codon-pair bias of the totiviral ORFs were highly variable with no similarities to the host ORFs.ConclusionsThere is a direct relation between the level of gene expression and codon usage and 3' context bias in X. dendrorhous, which is more evident for ORFs that are expressed at the highest levels under the studied conditions. However, there is no direct relation between the totiviral ORF biases and the host ORFs.
| S-EPMC4404019 | biostudies-literature
Project description:BACKGROUND: In many genomes, a clear preference in the usage of particular codons exists. The mechanisms that induce codon biases remain an open question; studies have attributed codon usage to translational selection, mutational bias and drift. Furthermore, correlations between codon usage within host genomes and their viral pathogens have been observed for a myriad of host-virus systems. As such, numerous studies have investigated codon usage and codon bias in an effort to better understand how species evolve. Numerous metrics have been developed to identify biases in codon usage. In addition, a few data repositories of codon bias data are available, differing in the metrics reported as well as the number and taxonomy of strains examined. DESCRIPTION: We have created a new web resource called the Codon Bias Database (CBDB) which provides information regarding the codon bias within the set of highly expressed genes for 300+ bacterial genomes. CBDB was developed to provide a resource for researchers investigating codon bias in bacteria, facilitating comparisons between strains and species. Furthermore, the site was created to serve those studying adaptation in phage; the genera selected for this first release of CBDB all have sequenced, annotated bacteriophages. The annotations and sequences for the highly expressed gene set are available for each strain in addition to the strain's codon bias measurements. CONCLUSIONS: Comparing species and strains provides a comprehensive look at how codon usage has been shaped over evolutionary time and can elucidate the putative mechanisms behind it. The Codon Bias Database provides a centralized repository of look-up tables and codon usage bias measures for a wide variety of genera, species and strains. Through our analysis of the variation in codon usage within the strains presently available, we find that most members of a genus have a codon composition most similar to other members of its genus, although not necessarily other members of its species.
| S-EPMC3463423 | biostudies-other
Project description:The codon composition of coding sequences plays an important role in the regulation of gene expression. Herein, we report systematic differences in the usage of synonymous codons among Arabidopsis thaliana genes that are expressed specifically in distinct tissues. Although we observed that both regionally and transcriptionally associated mutational biases were associated significantly with codon bias, they could not explain the observed differences fully. Similarly, given that transcript abundances did not account for the differences in codon usage, it is unlikely that selection for translational efficiency can account exclusively for the observed codon bias. Thus, we considered the possible evolution of codon bias as an adaptive response to the different abundances of tRNAs in different tissues. Our analysis demonstrated that in some cases, codon usage in genes that were expressed in a broad range of tissues was influenced primarily by the tissue in which the gene was expressed maximally. On the basis of this finding we propose that genes that are expressed in certain tissues might show a tissue-specific compositional signature in relation to codon usage. These findings might have implications for the design of transgenes in relation to optimizing their expression.
| S-EPMC3454886 | biostudies-other
Project description:Although the mapping of codon to amino acid is conserved across nearly all species, the frequency at which synonymous codons are used varies both between organisms and between genes from the same organism. This variation affects diverse cellular processes including protein expression, regulation, and folding. Here, we mathematically model an additional layer of complexity and show that individual codon usage biases follow a position-dependent exponential decay model with unique parameter fits for each codon. We use this methodology to perform an in-depth analysis on codon usage bias in the model organism Escherichia coli. Our methodology shows that lowly and highly expressed genes are more similar in their codon usage patterns in the 5'-gene regions, but that these preferences diverge at distal sites resulting in greater positional dependency (pD, which we mathematically define later) for highly expressed genes. We show that position-dependent codon usage bias is partially explained by the structural requirements of mRNAs that results in increased usage of A/T rich codons shortly after the gene start. However, we also show that the pD of 4- and 6-fold degenerate codons is partially related to the gene copy number of cognate-tRNAs supporting existing hypotheses that posit benefits to a region of slow translation in the beginning of coding sequences. Lastly, we demonstrate that viewing codon usage bias through a position-dependent framework has practical utility by improving accuracy of gene expression prediction when incorporating positional dependencies into the Codon Adaptation Index model.
| S-EPMC4069614 | biostudies-literature
Project description:We propose a simple, sensitive measure of synonymous codon usage bias, the Relative Codon Adaptation Index (rCAI), as a way to discriminate better between highly biased and unbiased regions, compared with the widely used Codon Adaptation Index (CAI). CAI is a geometric mean of the relative usage of codons in a gene, and is calculated using the codon usage table trained with a set of highly expressed genes. In contrast, rCAI is computed by subtracting the background codon usage trained with two noncoding frames of highly expressed genes from the codon usage in the coding frame. rCAI has higher signal-to-noise ratio than CAI, considering that noncoding frames would not show codon bias. Translation efficiency and protein abundance correlates comparably or better with rCAI than CAI or other measures such as 'effective number of codons' and 'SCUMBLE offsets'. Within overlapping coding regions, one of the two coding frames dominates in codon usage bias according to rCAI. Presumably, rCAI could substitute CAI in diverse applications.
| S-EPMC2880845 | biostudies-literature