Codon Bias Patterns of E. coli's Interacting Proteins.
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ABSTRACT:
SUBMITTER: Dilucca M
PROVIDER: S-EPMC4643964 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The genetic code is necessarily degenerate with 64 possible nucleotide triplets being translated into 20 amino acids. Eighteen out of the 20 amino acids are encoded by multiple synonymous codons. While synonymous codons are clearly equivalent in terms of the information they carry, it is now well established that they are used in a biased fashion. There is currently no consensus as to the origin of this bias. Drawing on ideas from stochastic thermodynamics we derive from first principles a mathematical model describing the statistics of codon usage bias. We show that the model accurately describes the distribution of codon usage bias of genomes in the fungal and bacterial kingdoms. Based on it, we derive a new computational measure of codon usage bias-the distance D capturing two aspects of codon usage bias: (i) differences in the genome-wide frequency of codons and (ii) apparent non-random distributions of codons across mRNAs. By means of large scale computational analysis of over 900 species across two kingdoms of life, we demonstrate that our measure provides novel biological insights. Specifically, we show that while codon usage bias is clearly based on heritable traits and closely related species show similar degrees of bias, there is considerable variation in the magnitude of D within taxonomic classes suggesting that the contribution of sequence-level selection to codon bias varies substantially within relatively confined taxonomic groups. Interestingly, commonly used model organisms are near the median for values of D for their taxonomic class, suggesting that they may not be good representative models for species with more extreme D, which comprise organisms of medical and agricultural interest. We also demonstrate that amino acid specific patterns of codon usage are themselves quite variable between branches of the tree of life, and that some of this variability correlates with organismal tRNA content.
| S-EPMC7061699 | biostudies-literature
Project description:Trends associated with codon usage in molluscum contagiosum virus (MCV) and factors governing the evolution of codon usage have not been investigated so far. In this study, attempts were made to decipher the codon usage trends and discover the major evolutionary forces that influence the patterns of codon usage in MCV with special reference to sub-types 1 and 2, MCV-1 and MCV-2, respectively. Three hypotheses were tested: (1) codon usage patterns of MCV-1 and MCV-2 are identical; (2) SCUB (synonymous codon usage bias) patterns of MCV-1 and MCV-2 slightly deviate from that of human host to avoid affecting the fitness of host; and (3) translational selection predominantly shapes the SCUB of MCV-1 and MCV-2. Various codon usage indices viz. relative codon usage value, effective number of codons and codon adaptation index were calculated to infer the nature of codon usage. Correspondence analysis and correlation analysis were performed to assess the relative contribution of silent base contents and significance of codon usage indices in defining bias in codon usage. Among the tested hypotheses, only the second and third hypotheses were accepted.
| S-EPMC8703355 | biostudies-literature
Project description:BackgroundCodon bias is a phenomenon of non-uniform usage of codons whereas codon context generally refers to sequential pair of codons in a gene. Although genome sequencing of multiple species of dipteran and hymenopteran insects have been completed only a few of these species have been analyzed for codon usage bias.Methods and principal findingsHere, we use bioinformatics approaches to analyze codon usage bias and codon context patterns in a genome-wide manner among 15 dipteran and 7 hymenopteran insect species. Results show that GAA is the most frequent codon in the dipteran species whereas GAG is the most frequent codon in the hymenopteran species. Data reveals that codons ending with C or G are frequently used in the dipteran genomes whereas codons ending with A or T are frequently used in the hymenopteran genomes. Synonymous codon usage orders (SCUO) vary within genomes in a pattern that seems to be distinct for each species. Based on comparison of 30 one-to-one orthologous genes among 17 species, the fruit fly Drosophila willistoni shows the least codon usage bias whereas the honey bee (Apis mellifera) shows the highest bias. Analysis of codon context patterns of these insects shows that specific codons are frequently used as the 3'- and 5'-context of start and stop codons, respectively.ConclusionsCodon bias pattern is distinct between dipteran and hymenopteran insects. While codon bias is favored by high GC content of dipteran genomes, high AT content of genes favors biased usage of synonymous codons in the hymenopteran insects. Also, codon context patterns vary among these species largely according to their phylogeny.
| S-EPMC3422295 | biostudies-literature
Project description:Choanoflagellates and filastereans are the closest known single celled relatives of Metazoa within Holozoa and provide insight into how animals evolved from their unicellular ancestors. Codon usage bias has been extensively studied in metazoans, with both natural selection and mutation pressure playing important roles in different species. The disparate nature of metazoan codon usage patterns prevents the reconstruction of ancestral traits. However, traits conserved across holozoan protists highlight characteristics in the unicellular ancestors of Metazoa. Presented here are the patterns of codon usage in the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta, as well as the filasterean Capsaspora owczarzaki. Codon usage is shown to be remarkably conserved. Highly biased genes preferentially use GC-ending codons, however there is limited evidence this is driven by local mutation pressure. The analyses presented provide strong evidence that natural selection, for both translational accuracy and efficiency, dominates codon usage bias in holozoan protists. In particular, the signature of selection for translational accuracy can be detected even in the most weakly biased genes. Biased codon usage is shown to have coevolved with the tRNA species, with optimal codons showing complementary binding to the highest copy number tRNA genes. Furthermore, tRNA modification is shown to be a common feature for amino acids with higher levels of degeneracy and highly biased genes show a strong preference for using modified tRNAs in translation. The translationally optimal codons defined here will be of benefit to future transgenics work in holozoan protists, as their use should maximise protein yields from edited transgenes.
| S-EPMC6188563 | 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:To study the roles of translational accuracy, translational efficiency, and the Hill-Robertson effect in codon usage bias, we studied the intragenic spatial distribution of synonymous codon usage bias in four prokaryotic (Escherichia coli, Bacillus subtilis, Sulfolobus tokodaii, and Thermotoga maritima) and two eukaryotic (Saccharomyces cerevisiae and Drosophila melanogaster) genomes. We generated supersequences at each codon position across genes in a genome and computed the overall bias at each codon position. By quantitatively evaluating the trend of spatial patterns using isotonic regression, we show that in yeast and prokaryotic genomes, codon usage bias increases along translational direction, which is consistent with purifying selection against nonsense errors. Fruit fly genes show a nearly symmetric M-shaped spatial pattern of codon usage bias, with less bias in the middle and both ends. The low codon usage bias in the middle region is best explained by interference (the Hill-Robertson effect) between selections at different codon positions. In both yeast and fruit fly, spatial patterns of codon usage bias are characteristically different from patterns of GC-content variations. Effect of expression level on the strength of codon usage bias is more conspicuous than its effect on the shape of the spatial distribution.
| S-EPMC1448744 | biostudies-literature
Project description:BackgroundThe expression of heterologous proteins in Escherichia coli is strongly affected by codon bias. This phenomenon occurs when the codon usage of the mRNA coding for the foreign protein differs from that of the bacterium. The ribosome pauses upon encountering a rare codon and may detach from the mRNA, thereby the yield of protein expression is reduced. Several bacterial strains have been engineered to overcome this effect. However, the increased rate of translation may lead to protein misfolding and insolubilization. In order to prove this assumption, the solubility of several recombinant proteins from plants was studied in a codon bias-adjusted E. coli strain.ResultsThe expression of eight plant proteins in Escherichia coli BL21(DE3)-pLysS and BL21(DE3)-CodonPlus-pRIL was systematically studied. The CodonPlus strain contains extra copies of the argU, ileY, and leuW tRNA genes, which encode tRNAs that recognize the codons AGA/AGG, AUA and CUA, respectively (RIL codons). The level of expression and solubility of the recombinant proteins were analyzed by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. We found that for all proteins the solubility was at least 25% in the BL21(DE3)-pLysS strain. However, when expressed in the BL21(DE3)-CodonPlus-pRIL strain, proteins having more than 5% of amino acids coded by RIL codons were localized mainly in the insoluble fraction. Also, their expression caused retarded growth and low cell yield in the codon bias-adjusted strain at all temperatures tested. On the contrary, the solubility of proteins containing less than 5% of amino acids coded by RIL codons remained unchanged in both strains and their expression caused no effect on cell growth.ConclusionOur results show that the expression of heterologous proteins coded by high RIL codon content coding sequences in a codon bias-adjusted strain is detrimental for their solubility. Our data support the hypothesis that the possible elimination of translational pauses that increase translation rate leads to protein misfolding and aggregation. This stresses the importance of strain selection according to codon content in any scheme where a large amount of biologically active product is desirable.
| S-EPMC2723077 | biostudies-literature
Project description:Human respiratory viruses are of vastly different virulence, giving rise to symptoms ranging from common cold to severe pneumonia or even death. Although this most likely impacts molecular evolution of the corresponding viruses, the specific differences in their evolutionary patterns remain largely unknown. By comparing structural and nonstructural genes within respiratory viruses, greater similarities in codon usage bias (CUB) between nonstructural genes and humans were observed in weakly virulent viruses, whereas in strongly virulent viruses, it was structural genes whose CUBs were more similar to that of humans. Further comparisons between genomes of weakly and strongly virulent coronaviruses revealed greater similarities in CUBs between strongly virulent viruses and humans. Finally, using phylogenetic independent contrasts, dissimilation of viral CUB from that of humans was observed in SARS-CoV-2. Our work revealed distinct CUB evolutionary patterns between weakly and strongly virulent viruses, a previously unrecognized interaction between CUB and virulence in respiratory viruses.
| S-EPMC8704784 | biostudies-literature
Project description:Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins--perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair--a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function--which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins--perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor--which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation.
| S-EPMC3179510 | 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