Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.
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ABSTRACT:
SUBMITTER: Mazumder TH
PROVIDER: S-EPMC4373688 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.
Mazumder Tarikul Huda TH Chakraborty Supriyo S
PloS one 20150325 3
TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed ...[more]
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Project description:BackgroundCodon usage bias (CUB) analysis is an effective method for studying specificity, evolutionary relationships, and mRNA translation and discovering new genes among various species. In general, CUB analysis is mainly performed within one species or between closely related species and no such study has been applied among species with distant genetic relationships. Here, seven Rosales species with high economic value were selected to conduct CUB analysis.ResultsThe results showed that the average GC1, GC2 and GC3 contents were 51.08, 40.52 and 43.12%, respectively, indicating that the A/T content is more abundant and the Rosales species prefer A/T as the last codon. Neutrality plot and ENc plot analysis revealed that natural selection was the main factor leading to CUB during the evolution of Rosales species. All 7 Rosales species contained three high-frequency codons, AGA, GTT and TTG, encoding Arg, Val and Leu, respectively. The 7 Rosales species differed in high-frequency codon pairs and the distribution of GC3, though the usage patterns of closely related species were more consistent. The results of the biclustering heat map among 7 Rosales species and 20 other species were basically consistent with the results of genome data, suggesting that CUB analysis is an effective method for revealing evolutionary relationships among species at the family or order level. In addition, chlorophytes prefer using G/C as ending codon, while monocotyledonous and dicotyledonous plants prefer using A/T as ending codon.ConclusionsThe CUB pattern among Rosales species was mainly affected by natural selection. This work is the first to highlight the CUB patterns and characteristics of Rosales species and provides a new perspective for studying genetic relationships across a wide range of species.
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Project description:The tumor suppressor gene TP53, one of the most frequently mutated genes, is recognized as the guardian of genome and can provide a significant barrier to neoplastic transformation and tumor progression. Traditional theory believes that TP53 mutations are equal among cancer types. However, to date, no study has explored the TP53 mutation profile from a holistic and systematic standpoint to discovery its relevance and feature with cancers. Mutation signature, an unbiased approach to identify the mutational processes, can be a potent indicator for exploring mutation-driven tumor occurrence and progression. In this research, several features such as hotspots, mutability and mutation signature of somatic TP53 mutations derived from 18 types of cancer tissues from cBioPortal were analyzed and manifested the organizational preference among cancers. Mutation signatures found in almost all cancer types were Signature 6 related to mismatch repair deficiency, and Signature 1 that reflects the natural decomposition of 5-methylcytosine into thymine associated with aging. Meanwhile, several signatures of TP53 mutations displayed tissue-selective. Mutations enriched in bladder, skin, lung cancer were associated with signatures of APOBEC activity (Signature 2 and 13), alkylating agents (Signature 11), and tobacco smoke (Signature 4), respectively. Moreover, Signature 4 and 29 associated with tobacco smoking or chewing found in lung, sarcoma, esophageal, and head and neck cancer may be related to their smoking history. In addition, several digestive cancers, including colorectal, stomach, pancreatic and esophageal cancers, showed the high correlation in context and mutation signature profiles. Our study suggests that the tissue-selective activity of mutational processes would reflect the tissue-specific enrichment of TP53 mutations and provides a new perspective to understand the relevance of diverse diseases based on the spectrum of TP53 mutations.
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Project description:BACKGROUND:Polyomaviruses (PyVs) have a wide range of hosts, from humans to fish, and their effects on hosts vary. The differences in the infection characteristics of PyV with respect to the host are assumed to be influenced by the biochemical function of the LT-Ag protein, which is related to the cytopathic effect and tumorigenesis mechanism via interaction with the host protein. METHODS:We carried out a comparative analysis of codon usage patterns of large T-antigens (LT-Ags) of PyVs isolated from various host species and their functional domains and sequence motifs. Parity rule 2 (PR2) and neutrality analysis were applied to evaluate the effects of mutation and selection pressure on codon usage bias. To investigate evolutionary relationships among PyVs, we carried out a phylogenetic analysis, and a correspondence analysis of relative synonymous codon usage (RSCU) values was performed. RESULTS:Nucleotide composition analysis using LT-Ag gene sequences showed that the GC and GC3 values of avian PyVs were higher than those of mammalian PyVs. The effective number of codon (ENC) analysis showed host-specific ENC distribution characteristics in both the LT-Ag gene and the coding sequences of its domain regions. In the avian and fish PyVs, the codon diversity was significant, whereas the mammalian PyVs tended to exhibit conservative and host-specific evolution of codon usage bias. The results of our PR2 and neutrality analysis revealed mutation bias or highly variable GC contents by showing a narrow GC12 distribution and wide GC3 distribution in all sequences. Furthermore, the calculated RSCU values revealed differences in the codon usage preference of the LT-AG gene according to the host group. A similar tendency was observed in the two functional domains used in the analysis. CONCLUSIONS:Our study showed that specific domains or sequence motifs of various PyV LT-Ags have evolved so that each virus protein interacts with host cell targets. They have also adapted to thrive in specific host species and cell types. Functional domains of LT-Ag, which are known to interact with host proteins involved in cell proliferation and gene expression regulation, may provide important information, as they are significantly related to the host specificity of PyVs.
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Project description:Miscanthus is not only a perennial fiber biomass crop, but also valuable breeding resource for its low-nutrient requirements, photosynthetic efficiency and strong adaptability to environment. In the present study, the codon usage patterns of five different Miscanthus plants and other two related species were systematically analyzed. The results indicated that the cp genomes of the seven representative species were preference to A/T bases and A/T-ending codons. In addition, 21 common high-frequency codons and 4-11 optimal codons were detected in the seven chloroplast genomes. The results of ENc-plot, PR2-plot and neutrality analysis revealed the codon usage patterns of the seven chloroplast genomes are influenced by multiple factors, in which nature selection is the main influencing factor. Comparative analysis of the codon usage frequencies between the seven representative species and four model organisms suggested that Arabidopsis thaliana, Populus trichocarpa and Saccharomyces cerevisiae could be considered as preferential appropriate exogenous expression receptors. These results might not only provide important reference information for evolutionary analysis, but also shed light on the way to improve the expression efficiency of exogenous gene in transgenic research based on codon optimization.
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Project description:Coding sequence evolution is influenced by both natural selection and neutral evolutionary forces. In many species, the effects of mutation bias, codon usage and GC-biased gene conversion (gBGC) on gene sequence evolution have not been detailed. Quantification of how these forces shape substitution patterns is therefore necessary to understand the strength and direction of natural selection. Here, we used comparative genomics to investigate the association between base composition and codon usage bias on gene sequence evolution in butterflies and moths (Lepidoptera), including an in-depth analysis of underlying patterns and processes in one species, Leptidea sinapis. The data revealed significant G/C to A/T substitution bias at third codon position with some variation in the strength among different butterfly lineages. However, the substitution bias was lower than expected from previously estimated mutation rate ratios, partly due to the influence of gBGC. We found that A/T-ending codons were overrepresented in most species, but there was a positive association between the magnitude of codon usage bias and GC-content in third codon positions. In addition, the tRNA-gene population in L. sinapis showed higher GC-content at third codon positions compared to coding sequences in general and less overrepresentation of A/T-ending codons. There was an inverse relationship between synonymous substitutions and codon usage bias indicating selection on synonymous sites. We conclude that the evolutionary rate in Lepidoptera is affected by a complex interaction between underlying G/C -> A/T mutation bias and partly counteracting fixation biases, predominantly conferred by overall purifying selection, gBGC and selection on codon usage.
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Project description:Background and Aims:Studies on codon usage in monocots have focused on grasses, and observed patterns of this taxon were generalized to all monocot species. Here, non-grass monocot species were analysed to investigate the differences between grass and non-grass monocots. Methods:First, studies of codon usage in monocots were reviewed. The current information was then extended regarding codon usage, as well as codon-pair context bias, using four completely sequenced non-grass monocot genomes (Musa acuminata, Musa balbisiana, Phoenix dactylifera and Spirodela polyrhiza) for which comparable transcriptome datasets are available. Measurements were taken regarding relative synonymous codon usage, effective number of codons, derived optimal codon and GC content and then the relationships investigated to infer the underlying evolutionary forces. Key Results:The research identified optimal codons, rare codons and preferred codon-pair context in the non-grass monocot species studied. In contrast to the bimodal distribution of GC3 (GC content in third codon position) in grasses, non-grass monocots showed a unimodal distribution. Disproportionate use of G and C (and of A and T) in two- and four-codon amino acids detected in the analysis rules out the mutational bias hypothesis as an explanation of genomic variation in GC content. There was found to be a positive relationship between CAI (codon adaptation index; predicts the level of expression of a gene) and GC3. In addition, a strong correlation was observed between coding and genomic GC content and negative correlation of GC3 with gene length, indicating a strong impact of GC-biased gene conversion (gBGC) in shaping codon usage and nucleotide composition in non-grass monocots. Conclusion:Optimal codons in these non-grass monocots show a preference for G/C in the third codon position. These results support the concept that codon usage and nucleotide composition in non-grass monocots are mainly driven by gBGC.
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Project description:Codon usage bias (CUB), the uneven use of synonymous codons, is a ubiquitous observation in virtually all organisms examined. The pattern of codon usage is generally similar among closely related species, but differs significantly among distantly related organisms, e.g., bacteria, yeast, and Drosophila. Several explanations for CUB have been offered and some have been supported by observations and experiments, although a thorough understanding of the evolutionary forces (random drift, mutation bias, and selection) and their relative importance remains to be determined. The recently available complete genome DNA sequences of twelve phylogenetically defined species of Drosophila offer a hitherto unprecedented opportunity to examine these problems. We report here the patterns of codon usage in the twelve species and offer insights on possible evolutionary forces involved.(1) Codon usage is quite stable across 11/12 of the species: G- and especially C-ending codons are used most frequently, thus defining the preferred codons. (2) The only amino acid that changes in preferred codon is Serine with six species of the melanogaster group favoring TCC while the other species, particularly subgenus Drosophila species, favor AGC. (3) D. willistoni is an exception to these generalizations in having a shifted codon usage for seven amino acids toward A/T in the wobble position. (4) Amino acids differ in their contribution to overall CUB, Leu having the greatest and Asp the least. (5) Among two-fold degenerate amino acids, A/G ending amino acids have more selection on codon usage than T/C ending amino acids. (6) Among the different chromosome arms or elements, genes on the non-recombining element F (dot chromosome) have the least CUB, while genes on the element A (X chromosome) have the most. (7) Introns indicate that mutation bias in all species is approximately 2:1, AT:GC, the opposite of codon usage bias. (8) There is also evidence for some overall regional bias in base composition that may influence codon usage.Overall, these results suggest that natural selection has acted on codon usage in the genus Drosophila, at least often enough to leave a footprint of selection in modern genomes. However, there is evidence in the data that random forces (drift and mutation) have also left patterns in the data, especially in genes under weak selection for codon usage for example genes in regions of low recombination. The documentation of codon usage patterns in each of these twelve genomes also aids in ongoing annotation efforts.
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