SEARCH · PubMed Health

Results for “Codon”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1988

Codon usage in selected AT-rich bacteria.

The relationship between DNA base composition and codon bias in very AT-rich bacteria was analyzed. Five clostridial genes, five mycoplasmal genes and three rickettsial genes constituted the data base. In the genes of these three organisms, the rule for codon bias was very simple: use U or A in the first and third positions of the codon when possible. This was contrasted with the bias found in Bacillus subtilis and Escherichia coli. The rule for Bacillus subtilis was equally straightforward: use all codons without bias. Only in E. coli, amongst the species examined, did the codon bias appear to be a complicated codon 'choice'.

Adenine↗

PubMed1981

Preferential codon usage in genes.

We present a method which permits comparison of the preferential use of degenerate codons within any gene. The method makes use of the triplet frequencies in the noncoding frames to assess whether a preference is specific to the reading frame. Preference is given a statistical meaning by use of the analysis of variance coupled to Duncan's multiple range test. Preferential use of degenerate codons is gene-specific and independent of gene size. The data suggest that any correlation between codon frequency distribution and tRNA levels is unreliable. In those animal genes examined, codons ending in C or G are preferred; in animal viruses tested, codons ending in U or A are preferred. Similarly, the bacterial genes and the genes of single-stranded DNA phages that we analyzed differed from each other as well as from eukaryotic genes in the third base of the codon.

Animals↗

PubMed1992

Codon usage in the G+C-rich Streptomyces genome.

The codon usage (CU) patterns of 64 genes from the Gram+ prokaryotic genus Streptomyces were analysed. Despite the extremely high overall G+C content of the Streptomyces genome (estimated at 0.74), individual genes varied in G+C content from 0.610 to 0.797, and had third codon position G+C contents (GC3s) that varied from 0.764 to 0.983. The variation in GC3s explains a significant proportion of the variation in CU patterns. This is consistent with an evolutionary model of the Streptomyces genome where biased mutation pressure has led to a high average G+C content with random variation about the mean, although the variation observed is greater than that expected from a simple binomial model. The only gene in the sample that can be confidently predicted to be highly expressed, EF-Tu of Streptomyces coelicolor A3(2) (GC3s = 0.927), shows a preference for a third position C in several of the four codon families, and for CGY and GGY for Arg and Gly codons, respectively (Y = pyrimidine); similar CU patterns are found in highly expressed genes of the G+C-rich Micrococcus luteus genome. It thus appears that codon usage in Streptomyces is determined predominantly by mutation bias, with weak translational selection operating only in highly expressed genes. We discuss the possible consequences of the extreme codon bias of Streptomyces and consider how it may have evolved. A set of CU tables is provided for use with computer programs that locate protein-coding regions.

Base Composition↗

PubMed1995

Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli.

Within Escherichia coli and other species, a clear codon bias exists among the 61 amino acid codons found within the population of mRNA molecules, and the level of cognate tRNA appears directly proportional to the frequency of codon usage. Given this situation, one would predict translational problems with an abundant mRNA species containing an excess of rare low tRNA codons. Such a situation might arise after the initiation of transcription of a cloned heterologous gene in the E. coli host. Recent studies suggest clusters of AGG/AGA, CUA, AUA, CGA or CCC codons can reduce both the quantity and quality of the synthesized protein. In addition, it is likely that an excess of any of these codons, even without clusters, could create translational problems.

Arginine↗

PubMed2005

Translational effects of differential codon usage among intragenic domains of new genes in Drosophila.

Evolved codon usages often pose a technical challenge over the expressing of eukaryotic genes in microbial systems because of changed translational machinery. In the present study, we investigated the translational effects of intragenic differential codon usage on the expression of the new Drosophila gene, jingwei (jgw), a chimera derived from two unrelated parental genes: Ymp and Adh. We found that jgw possesses a strong intragenic differential usage of synonymous codons, i.e. the Adh-derived C-domain has a significantly higher codon bias than that of the Ymp-derived N-domain (P=0.0023 by t-test). Additional evolutionary analysis revealed the heterogeneous distribution of rare codons, implicating its role in gene regulation and protein translation. The in vitro expression of jgw further demonstrated that the heterogeneous distribution of rare codons has played a role in regulating gene expression, particularly, affecting the quality of protein translation.

Alcohol Dehydrogenase↗

PubMed2004

The relationship between synonymous codon usage and protein structure in Escherichia coli and Homo sapiens.

The role of silent position in the codon on the protein structure is an interesting and yet unclear problem. In this paper, 563 Homo sapiens genes and 417 Escherichia coli genes coding for proteins with four different folding types have been analyzed using variance analysis, a multivariate analysis method newly used in codon usage analysis, to find the correlation between amino acid composition, synonymous codon, and protein structure in different organisms. It has been found that in E. coli, both amino acid compositions in differently folded proteins and synonymous codon usage in different gene classes coding for differently folded proteins are significantly different. It was also found that only amino acid composition is different in different protein classes in H. sapiens. There is no universal correlation between synonymous codon usage and protein structure in these two different organisms. Further analysis has shown that GC content on the second codon position can distinguish coding genes for different folded proteins in both organisms.

Amino Acid Sequence↗

PubMed2004

Selection on codon usage in Drosophila americana.

Synonymous codons are not used at random, significantly influencing the base composition of the genome. The selection-mutation-drift model proposes that this bias reflects natural selection in favor of a subset of preferred codons. Previous estimates in Drosophila of the intensity of selective forces involved seem too large to be reconciled with theoretical predictions of the level of codon bias. This probably results from confounding effects of the demographic histories of the species concerned. We have studied three species of the virilis group of Drosophila, which are more likely to satisfy the assumptions of the evolutionary models. We analyzed the patterns of polymorphism and divergence in a sample of 18 genes and applied a new method for estimating the intensity of selection on synonymous mutations based on the frequencies of unpreferred mutations among polymorphic sites. This yielded estimates of selection intensities (N(e)s) of the order of 0.65, which is more compatible with the observed levels of codon bias. Our results support the action of both selection and mutational bias on codon usage bias and suggest that codon usage and genome base composition in the D. americana lineage are in approximate equilibrium. Biased gene conversion may also contribute to the observed patterns.

Animals↗

PubMed2005

TGF-beta1 codon 25 gene polymorphism is associated with cirrhosis in patients with hereditary hemochromatosis.

Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism with variable penetrance. Only a minority of C282Y homozygotes develop clinical overt disease and cirrhosis. The phenotypic heterogeneity of HHC may be due to host genetic factors influencing fibrogenesis such as cytokine gene polymorphisms. In this respect, we investigated the impact of functional genetic polymorphisms of TGF-beta1 (codon 10 Leu/Pro, codon 25 Arg/Pro), TNF-alpha (-308 G/A, -238 G/A) and angiotensinogen (-6 G/A) on the development of cirrhosis in HHC. One hundred and forty-nine (111 male, mean age: 51.0+/-12.9) C282Y homozygotes who underwent liver biopsy were studied. Genotyping was performed by RFLP analysis. TGF-beta1 codon 25 genotypes Arg/Pro and Pro/Pro were more common in patients with cirrhosis than in those without (23.6% vs. 7.4%, p = 0.005). In contrast, the distribution of TGF-beta1 codon 10, TNF-alpha and angiotensinogen genotypes was not different. Logistic regression analysis identified male sex, age, serum ferritin and TGF-beta1 codon 25 Arg/Pro and Pro/Pro as independent predictors for the presence of cirrhosis. The adjusted odds ratio for TGF-beta1 codon 25 Arg/Pro and Pro/Pro was 2.8 (95% CI 1.4-5.7, p = 0.004). In conclusion, C282Y homozygotes carrying TGF-beta1 genotypes Arg/Pro and Pro/Pro are more likely to develop cirrhosis than those with genotype Arg/Arg.

Adult↗

PubMed2006

Over-representation of Chi sequences caused by di-codon increase in Escherichia coli K-12.

Chi sequences (5'-GCTGGTGG-3') are cis-acting 8 bp sequence elements that enhance homologous recombination promoted by the RecBCD pathway in Escherichia coli. The genome of E. coli K-12 MG1655 contains 1009 Chi sequences and this frequency far exceeds the expected value for occurrence of an 8 bp sequence in a genome of this size. It is generally thought that the over-representation of Chi sequences indicates that they have been selected for during evolution because of their function in recombination. The genes from three E. coli strains (K-12, O157 and CFT) were classified into three categories (island, match to other E. coli, and backbone). Island genes have a different base composition and codon usage in comparison with those in the backbone genes, therefore they were relatively new and not yet adapted to the base composition patterns and codon usage typical of the recipient genome. The over-representation of Chi sequences was examined by comparing Chi frequencies and codon frequencies between island and backbone genes. The difference in the CTGGTG di-codon frequency between the backbone and island genes was correlated with the frequency of Chi sequences which were translated in the Leu-Val (-G/CTG/GTG/G-) reading frame in the K-12 strain. These results suggest that the main reading frame of Chi sequences increased as a result of the di-codon CTG-GTG increasing under a genome-wide pressure for adapting to the codon usage and base composition of the E. coli K-12 strain, and that the RecBCD recombinase might adjust its recognition sequence to a frequently occurring oligomer such as G-CTG-GTG-G.

Base Composition↗

PubMed2006

AT2-AT3-profiling: a new look at synonymous codon usage.

The teleology of synonymous codon usage (SCU) still awaits a unifying concept. Here the 2nd codon letter of human mRNA-codons was graphically, aided by a computer program, put in relation to the 3rd codon letter, the carrier of SCU: AT2, the density of A+T in 2nd codon position, behaves to AT3, the analogous density of the 3rd codon position, mostly in an inverse fashion that can be expressed as typical figures: mRNAs with an overall AT-density below 50% have a tendency to produce bulky figures called "red dragons" (when redness is attributed to graph-areas, where AT3< AT2), while mRNAs with an AT-density above 50% produce a pattern called "harlequin" consisting of alternating red and blue (blueness, in analogy, when AT3>AT2) diamonds. With more diversion of AT3 from AT2, the harlequin patterns can assume the pattern of a "blue dragon". By analysing the mRNA of known proteins, these patterns can be correlated with certain functional regions: proteins with multiple transmembrane passages show bulky "red dragons", structural proteins with a high glycine- and proline content such as collagen result in "blue dragons". Non-coding mRNAs tend to show a balance between AT2 and AT3 and hence "harlequin patterns". Signal peptides usually code red due to a low AT3 with an AT2-density at the expectance level. With this technique DNA-sequences of as yet unknown functional meaning were scanned. When stretches of harlequin patterns appear interrupted by red or blue dragons, closer scrutiny of these stretches can reveal ORFs which deserve to be looked at more closely for their protein-informational content. At least in humans, SCU appears to follow protein-dependent AT2-density in a reciprocal fashion and does not seem to serve the purpose of influencing mRNA secondary structure which is discussed in depth.

Animals↗

PubMed2004

Lack of association between Caucasian lung cancer risk and O6-methylguanine-DNA methyltransferase-codon 178 genetic polymorphism.

The formation of DNA adducts is thought to be a critical step for the induction of chemically induced cancer. O(6)-Methylguanine-DNA methyltransferase (MGMT) is a ubiquitously expressed enzyme that repairs DNA adducts formed by alkylating carcinogens. Thus, genetic polymorphisms of the MGMT that could result in differences in MGMT activity are potential risk factors for cancer. In the present study, we established a convenient and reliable genotyping method for the MGMT codon 178 polymorphism, a Lys (AAG) to Arg (AGG) substitution, using restriction fragment length polymorphism (RFLP), and studied differences in the distribution of this polymorphism in 92 Caucasian lung cancer patients and 85 controls. Frequencies of the "A" and "G" alleles (MGMT codon 178, AAG and AGG, respectively) were 0.91 and 0.09, respectively. The genetic polymorphism of the MGMT codon 178 was linked with that of the MGMT codon 143 (P < 0.05). The distribution of the MGMT codon 178 genetic polymorphism was not significantly different between lung cancer patients and controls. Thus, our study suggests that the MGMT codon 178 (and possibly 143) polymorphisms do not appear to markedly affect lung cancer risk for this population. In addition, we found an apparent 10bp-deletion in the intron before exon 5 by DNA sequencing. Because this "deletion" was observed in all sequenced samples (N = 20), the previously reported human (Caucasian) MGMT gene sequence should be revised to exclude this 10bp segment.

Codon↗

PubMed2005

A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codon.

During eukaryotic translation initiation, ribosomal 43S complexes scan mRNAs for the correct AUG codon at which to begin translation. Start codon recognition triggers GTP hydrolysis, committing the complex to engagement at that point on the mRNA. While fidelity at this step is essential, the nature of the codon recognition event and the mechanism by which it activates GTP hydrolysis are poorly understood. Here we report the changes that occur within the 43S.mRNA complex in response to AUG codon recognition. eIF1 and eIF1A are key players in assembly of 43S.mRNA complexes capable of locating initiation codons. We observed FRET between these two factors when bound to the 40S subunit. Using steady-state FRET, anisotropy, and kinetic analyses, we demonstrate that start codon recognition results in a conformational change and release of eIF1 from the ribosome. These rearrangements probably play a role in triggering GTP hydrolysis and committing the complex to downstream events.

Codon, Initiator↗

PubMed2005

The associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer.

Variations in p53 codon 72 have been identified as significant predisposing factors for various cancers, but molecular mechanisms remain unclear. We investigated associations of p53 overexpression with codon 72 variants and other factors with esophageal cancer. Status of p53 overexpression was determined by immunohistochemical staining. Codon 72 polymorphisms and mutation of p53 was identified by PCR-RFLP and direct sequencing from exons 4 to 9, respectively. We evaluated 126 patients who underwent esophagectomy in the National Taiwan University Hospital, and found that the status of p53 overexpression was significantly influenced by presence of codon 72 polymorphisms. After adjustment for other possible confounders, the incidence of p53 overexpression was significantly decreased in patients with Pro/Pro genotype with an odds ratio (OR) of 0.21 (95% CI: 0.067-0.64) (p = 0.0065) compared with incidence in patients with Arg/Arg genotype. The incidence of p53 overexpression was additively increased with environmental exposure to cigarette smoke, alcohol, and areca quid. When compared with individuals exposed to only one of these environmental risk factors, patients who had exposure to two or three risk factors had ORs of 6.11 (95% CI: 1.80-20.75) and 6.22 (95% CI: 1.81-21.34) for p53 overexpression, respectively. Elderly patients (age >70 years) were also more likely to have p53 overexpression, with an OR of 5.63 (95% CI: 1.53-20.64) compared with overexpression among patients aged less than 55 years. Forty-one patients received further evaluation of p53 mutation. There was also a higher incidence of, but without reaching a statistical significance, p53 mutation in patients with p53 overexpression (OR[95% CI]: 2.18 [0.52-9.6]) and codon 72 Arg/Arg genotype (OR [95% CI] of 0.8 [0.13-4.2], comparing genotypes of Pro/Pro and Arg/Pro with Arg/Arg). Our data provide the first observations that the presence of p53 codon 72 variants can be a significant factor influencing p53 overexpression in esophageal cancer, with overexpression also influenced by combined or prolonged environmental exposures.

Aged↗

PubMed2004

Intranasal administration of an Escherichia coli-expressed codon-optimized rotavirus VP6 protein induces protection in mice.

We are developing rotavirus vaccines based on the VP6 protein of the human G1P[8] [corrected] [J. Virol. 73 (1999) 7574] CJN strain of rotavirus. One prototype candidate consisting of MBP::VP6::His6, a chimeric protein of maltose-binding protein, VP6 and hexahistidine, was expressed mainly as truncated polypeptides in Escherichia coli BL21(DE3) cells. A possible reason for this extensive truncation is the high frequencies of rare bacterial codons within the rotavirus VP6 gene. Expression of truncated recombinant VP6 was found to be reduced, and expression of complete VP6 protein was simultaneously increased, when the protein was expressed in Rosetta(DE3)pLacI E. coli cells that contain increased amounts of transfer RNAs for a selection of rare codons. The same observation was made when a synthetic codon-optimized CJN-VP6 gene was expressed in E. coli BL21 or Rosetta cells. To increase protein recovery, recombinant E. coli cells were treated with 8M urea. Denatured, full-length MBP::VP6::His6 protein was then purified and used for intranasal vaccination of BALB/c mice (2 doses administered with E. coli heat-labile toxin LT(R192G) as adjuvant). Following oral challenge with the G3P[16] [corrected] [J. Virol. 76 (2002) 560] EDIM strain of murine rotavirus, protection levels against fecal rotavirus shedding were comparable (P>0.05) between groups of mice immunized with denatured codon-optimized or native (not codon-optimized) immunogen with values ranging from 87 to 99%. These protection levels were also comparable to those found after immunization with non-denatured CJN VP6. Thus, expression of complete rotavirus VP6 protein was greatly enhanced by codon optimization, and the protection elicited was not affected by denaturation of recombinant VP6.

Administration, Intranasal↗

PubMed2005

Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP(5) glycoprotein and improves immune response in challenged pigs.

Pigs exposed to GP(5) protein of PRRSV by means of DNA immunization develop specific neutralizing and protecting antibodies. Herein, we report on the consequences of codon bias, and on the favorable outcome of the systematic replacement of native codons of PRRSV ORF5 gene with codons chosen to reflect more closely the codon preference of highly expressed mammalian genes. Therefore, a synthetic PRRSV ORF5 gene (synORF5) was constructed in which 134 nucleotide substitutions were made in comparison to wild-type gene (wtORF5), such that 59% (119) of wild-type codons were replaced with known preferable codons in mammalian cells. In vitro expression in mammalian cells of synORF5 was considerably increased comparatively to wtORF5, following infection with tetracycline inducible replication-defective human adenoviral vectors (hAdVs). After challenge inoculation, SPF pigs vaccinated twice with recombinant hAdV/synORF5 developed earlier and higher antibody titers, including virus neutralizing antibodies to GP(5) than pigs vaccinated with hAdV/wtORF5. Data obtained from animal inoculation studies suggest direct correlation between expression levels of immunogenic structural viral proteins and immune response.

Animals↗

PubMed2005

Synonymous codon usage bias in 16 Staphylococcus aureus phages: implication in phage therapy.

To reveal the factors influencing architecture of protein-coding genes in staphylococcal phages, relative synonymous codon usage variation has been investigated in 920 protein-coding genes of 16 staphylococcal phages. As expected for AT rich genomes, there are predominantly A and T ending codons in all 16 phages. Both Nc plot and correspondence analysis on relative synonymous codon usage indicates that mutation bias influences codon usage variation in the 16 phages. Correspondence analysis also suggests that translational selection and gene length also influence the codon usage variation in the phages to some extent and codon usage in staphylococcal phages is phage-specific but not S. aureus-specific. Further analysis indicates that among 16 staphylococcal phages, 44AHJD, P68 and K may be extremely virulent in nature as most of their genes have high translation efficiency. If this is true, then above three phages may be useful for curing staphylococcal infections.

Animals↗

PubMed2005

Synonymous codon usage in adenoviruses: influence of mutation, selection and protein hydropathy.

Trends in synonymous codon usage in adenoviruses have been examined through the multivariate statistical analysis on the annotated protein-coding regions of 22 adenoviral species, for which complete genome sequences are available. One of the major determinants of such trends is the G+C content at third codon positions of the genes, the average value of which varied from one viral genome to other depending on the overall mutational bias of the species. G3S and C3S interacted synergistically along the first principal axis of correspondence analysis on the Relative Synonymous Codon Usage of adenoviral genes, but antagonistically along the second principal axis. The intra-genomic variation in codon usage pattern in adenoviruses is generally influenced by asymmetrical mutational bias in two DNA strands. Other major determinants of the trends are the natural selection, putatively operative at the level of translation and quite interestingly, hydropathy of the encoded proteins. The trends in codon usage, though characterized by distinct virus-specific mutational bias, do not exhibit any sign of host-specificity. Significant variations are observed in synonymous codon choice in structural and nonstructural genes of adenoviruses.

Adenoviridae↗

PubMed2006

Efficient expression of the 15-kDa form of infectious pancreatic necrosis virus VP5 by suppression of a UGA codon.

Infectious pancreatic necrosis virus (IPNV), a member of the Birnaviridae family, encodes a nonstructural VP5 protein from a small open reading frame (ORF), which overlaps with a major ORF encoding pVP2, VP4 and VP3 proteins. In majority of the Sp strains of IPNV sequenced to date, VP5 gene codes for a 15-kDa protein. However, we have shown that in highly virulent strains, there is a premature in-frame stop codon (UGA) at nucleotide (nt) position 427, (preceding the 15-kDa stop codon at nt position 511) which could encode a 12-kDa protein. Using reverse genetics, we recovered recombinant rNVI15, rNVI15-15K and rNVI15-DeltaVP5 viruses (which could encode 12 or 15-kDa VP5 or lack the expression of VP5, respectively) and demonstrated that VP5 is dispensable for viral replication in vivo but is not involved in virulence (Santi, N., Song, H., Vakharia, V. N., Evensen, Ø., 2005a. Infectious pancreatic necrosis virus VP5 is dispensable for virulence and persistence. J. Virol. 79, 9206-9216). Here, we utilized these viruses to investigate the gene expression of VP5 in vitro. Our results indicate that a 15-kDa VP5 is produced in rNVI15-infected cells, albeit at lower levels than in rNVI15-15K-infected cells, suggesting that the opal stop codon at nt 427 is suppressed. Furthermore, to examine translational suppression of the opal stop codon in VP5 gene, we constructed plasmids containing VP5-specific sequence and employed a yeast-based bicistronic dual-luciferase reporter system (Harger, J.W., Dinman, J.D., 2003. An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae. RNA 9, 1019-1024). Our results demonstrate that the VP5 sequence (with or without a stop codon) yielded approximately 13% termination suppression and the efficiency is directly related to the base immediately 3' of the termination codon, C>A>U>G.

Animals↗