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At least 145 records · Page 8Linked to original sources
PubMed1999

Codon bias and mutability in HIV sequences.

A survey of the patterns of synonymous codon preference in the HIV env gene reveals a correlation between the codon bias and the mutability requirements of different regions of the protein. At hypervariable regions in gp120 one finds a greater proportion of codons that tend to mutate nonsynonymously, but to a target that is similar in hydrophobicity and volume. We argue that this strategy results from a compromise between the selective pressure placed on the virus by the induced immune response, which favors amino acid substitutions in the complementarity determining regions, and the negative selection against missense mutations that violate structural constraints of the env protein.

Codon↗
PubMed1996

Ribosome-mediated translational pause and protein domain organization.

Because regions on the messenger ribonucleic acid differ in the rate at which they are translated by the ribosome and because proteins can fold cotranslationally on the ribosome, a question arises as to whether the kinetics of translation influence the folding events in the growing nascent polypeptide chain. Translationally slow regions were identified on mRNAs for a set of 37 multidomain proteins from Escherichia coli with known three-dimensional structures. The frequencies of individual codons in mRNAs of highly expressed genes from E. coli were taken as a measure of codon translation speed. Analysis of codon usage in slow regions showed a consistency with the experimentally determined translation rates of codons; abundant codons that are translated with faster speeds compared with their synonymous codons were found to be avoided; rare codons that are translated at an unexpectedly higher rate were also found to be avoided in slow regions. The statistical significance of the occurrence of such slow regions on mRNA spans corresponding to the oligopeptide domain termini and linking regions on the encoded proteins was assessed. The amino acid type and the solvent accessibility of the residues coded by such slow regions were also examined. The results indicated that protein domain boundaries that mark higher-order structural organization are largely coded by translationally slow regions on the RNA and are composed of such amino acids that are stickier to the ribosome channel through which the synthesized polypeptide chain emerges into the cytoplasm. The translationally slow nucleotide regions on mRNA possess the potential to form hairpin secondary structures and such structures could further slow the movement of ribosome. The results point to an intriguing correlation between protein synthesis machinery and in vivo protein folding. Examination of available mutagenic data indicated that the effects of some of the reported mutations were consistent with our hypothesis.

Bacterial Proteins↗
PubMed1999

The evolution of codon preferences in Drosophila: a maximum-likelihood approach to parameter estimation and hypothesis testing.

Synonymous codon usage in related species may differ as a result of variation in mutation biases, differences in the overall strength and efficiency of selection, and shifts in codon preference-the selective hierarchy of codons within and between amino acids. We have developed a maximum-likelihood method to employ explicit population genetic models to analyze the evolution of parameters determining codon usage. The method is applied to twofold degenerate amino acids in 50 orthologous genes from D. melanogaster and D. virilis. We find that D. virilis has significantly reduced selection on codon usage for all amino acids, but the data are incompatible with a simple model in which there is a single difference in the long-term Ne, or overall strength of selection, between the two species, indicating shifts in codon preference. The strength of selection acting on codon usage in D. melanogaster is estimated to be |Nes| approximately 0.4 for most CT-ending twofold degenerate amino acids, but 1.7 times greater for cysteine and 1.4 times greater for AG-ending codons. In D. virilis, the strength of selection acting on codon usage for most amino acids is only half that acting in D. melanogaster but is considerably greater than half for cysteine, perhaps indicating the dual selection pressures of translational efficiency and accuracy. Selection coefficients in orthologues are highly correlated (rho = 0.46), but a number of genes deviate significantly from this relationship.

Amino Acids↗
PubMed2000

In vivo misreading by tRNA overdose.

Rpb5-H147R is an AT-GC transition replacing CAC(His) by CGC(Arg) at a conserved and critical position of ABC27 (Rpb5p), one of the five common and essential subunits shared by all three eukaryotic RNA polymerases. This mutation is viable at 25 degrees C, but has a lethal phenotype at 34 degrees C. A search for dosage-dependent suppressors identified five distinct clones that all bear a copy of the tRNA(His)GUG gene. Suppression was also observed with a small genomic insert bearing this tRNA gene and no other coding sequences, under conditions where there is a sevenfold increase in the cellular concentration of tRNA(His)GUG. Overexpressing tRNA(Arg)ICG, which normally decodes the suppressed CGC codon, counteracted suppression. Suppression is codon specific because it was abolished when replacing CGC by its synonymous codons CGA, CGU, or AGA, but was not detectably affected by several nucleotide substitutions modifying the surrounding sequence and is thus largely insensitive to the nucleotide context. It is proposed that overexpressing tRNA(His)GUG extends its decoding properties from CAC(His) to the noncognate CGC(Arg) codon through an illegitimate U x G pairing at the middle base of the anticodon. Accordingly, tRNA(His)GUG would compete with tRNA(Arg)ICG for chain elongation and generate a significant level of misreading errors under normal growth conditions.

Anticodon↗
PubMed1998

Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli.

The relationship between gene length and synonymous codon usage bias was investigated in Drosophila melanogaster, Escherichia coli and Saccharomyces cerevisiae. Simulation studies indicate that the correlations observed in the three organisms are unlikely to be due to sampling errors or any potential bias in the methods used to measure codon usage bias. The correlation was significantly positive in E.coli genes, whereas negative correlations were obtained for D. melanogaster and S.cerevisiae genes. When only ribosomal protein genes were used, whose expression levels are assumed to be similar, E.coli and S.cerevisiae showed significantly positive correlations. For the two eukaryotes, the distribution of effective number of codons was different in short genes (300-500 bp) compared with longer genes; this was not observed in E.coli. Both positive and negative correlations can be explained by translational selection. Energetically costly longer genes have higher codon usage bias to maximize translational efficiency. Selection may also be acting to reduce the size of highly expressed proteins, and the effect is particularly pronounced in eukaryotes. The different relationships between codon usage bias and gene length observed in prokaryotes and eukaryotes may be the consequence of these different types of selection.

Animals↗
PubMed1987

Adjustment of the tRNA population to the codon usage in chloroplasts.

In chloroplasts there is a correlation between the amounts of tRNAs specific for a given amino acid and the codons specifying this amino acid. Furthermore, for the amino acids coded for by more than one codon, the population of isoaccepting tRNAs is adjusted to the frequency of synonymous codons used in chloroplast protein genes. A comparison by two-dimensional gel electrophoresis of the tRNA populations extracted from chloroplasts and from chloroplast polysomes shows that all chloroplast tRNAs are involved in protein biosynthesis.

Chloroplasts↗
PubMed1991

Nucleotide sequence of the Escherichia coli recJ chromosomal region and construction of recJ-overexpression plasmids.

The nucleotide sequence of the recJ gene of Escherichia coli K-12 and two upstream coding regions was determined. Three regions were identified within these two upstream genes that exhibited weak to moderate promoter activity in fusions to the galK gene and are candidates for the recJ promoter. recJ appeared to be poorly translated: the recJ nucleotide sequence revealed a suboptimal initiation codon GUG, no discernible ribosome-binding consensus sequence, and relatively nonbiased synonymous codon usage. Comparison of the sequence of this region of the chromosome with DNA data bases identified the gene immediately downstream of recJ as prfB, which encodes translational release factor 2 and has been mapped near recJ at 62 min. No significant homology between recJ and other previously sequenced regions of DNA was detected. However, protein sequence comparisons with a gene upstream of recJ, denoted xprB, revealed significant homology with several site-specific recombination proteins. Its genetic function is presently unknown. Knowledge of the nucleotide sequence of recJ allowed the construction of a plasmid from which overexpression of RecJ protein could be induced. Supporting the notion that translation of recJ is limiting, a strong T7 bacteriophage promoter upstream of recJ did not, by itself, allow high-level expression of RecJ protein. The addition of a ribosome-binding sequence fused to the initiator GTG of recJ in this construction was necessary to promote expression of high levels of RecJ protein.

Amino Acid Sequence↗
PubMed1986

Structure of the Escherichia coli K12 regulatory gene tyrR. Nucleotide sequence and sites of initiation of transcription and translation.

The nucleotide sequence of 1964 base pairs of the Escherichia coli K12 chromosome containing the autogenously regulated regulatory gene tyrR has been determined. The site of initiation of transcription of tyrR has been mapped by primer-extension analysis, and the initiation codon has been identified by site-specific deletion mutagenesis. The nucleotide sequence predicts a subunit molecular weight of 53,099 for the TyrR protein. Codon usage in the tyrR structural gene shows a bias toward those synonymic codons which are used rarely in efficiently expressed E. coli genes. The nucleotide sequence of a 22-base pair region adjacent to the promoter and distal to the structural gene exhibits considerable identity with corresponding regions of other genes regulated by tyrR. It is proposed that this is a site for repression by the TyrR protein.

Amino Acid Sequence↗
PubMed1992

DNA sequence variability at the rplX locus of Bacillus subtilis.

The pattern and extent of DNA sequence variability at the rplX locus (encoding ribosomal protein L24) has been investigated in nine strains of Bacillus subtilis. Overall, there is a very low level of nucleotide diversity, even at silent sites, which is probably due to selection among synonymous codons. By analogy with Escherichia coli, there may also be some effect of the relative proximity of rplX to the chromosomal origin of replication. The small number of nucleotide substitutions are non-randomly distributed: all of the synonymous changes are in valine codons. From the sequence differences the strains can be divided into two groups, which are not coincident with their previous classification; this observation is consistent with recombination among strains.

Amino Acid Sequence↗
PubMedDate not supplied

Codon equilibrium II: Its use in estimating silent-substitution rates.

We study the equilibrium in the use of synonymous codons by eukaryotic organisms and find five equations involving substitution rates that we believe embody the important implications of equilibrium for the process of silent substitution. We then combine these five equations with additional criteria to determine sets of substitution rates applicable to eukaryotic organisms. One method employs the equilibrium equations and a principle of maximum entropy to find the most uniform set of rates consistent with equilibrium. In a second method we combine the equilibrium equations with data on the man-mouse divergence to determine that set of rates that is most neutral yet consistent with both types of data (i.e., equilibrium and divergence data). Simulations show this second method to be quite reliable in spite of significant saturation in the substitution process. We find that when divergence data are included in the calculation of rates, even though these rates are chosen to be as neutral as possible, the strength of selection inferred from the nonuniformity of the rates is approximately doubled. Both sets of rates are applied to estimate the human-mouse divergence time based on several independent subsets of the divergence data consisting of the quartet, C- or T-ending duet, and A- or G-ending duet codon sets. Both rate sets produce patterns of divergence times that are shortest for the quartet data, intermediate for the CT-ending duets, and longest for the AG-ending duets. This indicates that rates of transitions in the duet-codon sets are significantly higher than those in the quartet-codon sets; this effect is especially marked for A----G, the rate of which in duets must be about double that in quartets.

Animals↗
PubMed1997

Rare codons are not sufficient to destabilize a reporter gene transcript in tobacco.

In plants, as in other eukaryotes, most synonymous codons of the genetic-code are not used with equal frequency, but instead some codons are preferred, whereas others are rare. Circumstantial evidence led to the suggestion that rare codons have a negative influence on mRNA stability. To address this question experimentally, rare codons encoded by a Bacillus thuringiensis (B.t.) toxin gene (cryIA(c)) or a synthetic sequence were introduced into a phytohemagglutinin (PHA) reporter gene. In neither case was the mRNA stability appreciably diminished in stably transformed tobacco cell cultures nor was the accumulation of mRNA in transgenic plants affected. Thus rare codons do not appear to be sufficient to cause rapid degradation of the PHA mRNA and potentially other mRNAs in plants.

Cell Line↗
PubMed1990

Codon discrimination due to presence of abundant non-cognate competitive tRNA.

It has been thought that preferential use of synonymous codons provides high efficiency and fidelity of protein synthesis through specific codon-anticodon interactions. In yeast genes, some codon boxes seem to prefer a codon which is unsuited for its cognate anticodon. Now, we propose that codon usage biases may arise due to presence of abundant non-cognate competitive tRNA capable of misreading a codon by C-U or G-U pairing in the middle position.

Codon↗
PubMed1998

Silent mutations in the Escherichia coli ompA leader peptide region strongly affect transcription and translation in vivo.

In order to test the effect of silent mutations on the regulation of gene expression, we monitored several steps of transcription and translation of the ompA gene in vivo , in which some or all codons between codons 6 and 14, frequently used in Escherichia coli , had been exchanged for infrequent synonymous codons. Northern blot analysis revealed an up to 4-fold reduction in the half-life of the mutated messengers and a >10-fold reduction in their steady-state amounts. Western blot analysis showed a 10-fold reduction in the amount of OmpA protein. Use of a system expressing a Rho-specific anti-terminator allowed us to detect a strong transcription polarity effect in the silent mutants. These results demonstrate that silent mutations can severely inhibit several steps of gene expression in E. coli and that code degeneracy is efficiently exploited in this species for setting signals for gene control and regulation.

Bacterial Outer Membrane Proteins↗
PubMed1993

Reduced synonymous substitution rate at the start of enterobacterial genes.

Synonymous codon usage is less biased at the start of Escherichia coli genes than elsewhere. The rate of synonymous substitution between E.coli and Salmonella typhimurium is substantially reduced near the start of the gene, which suggests the presence of an additional selection pressure which competes with the selection for codons which are most rapidly translated. Possible competing sources of selection are the presence of secondary ribosome binding sites downstream from the start codon, the avoidance of mRNA secondary structure near the start of the gene and the use of sub-optimal codons to regulate gene expression. We provide evidence against the last of these possibilities. We also show that there is a decrease in the frequency of A, and an increase in the frequency of G along the E.coli genes at all three codon positions. We argue that these results are most consistent with selection to avoid mRNA secondary structure.

Base Composition↗
PubMed1983

The nucleotide sequence of the rat cytoplasmic beta-actin gene.

The nucleotide sequence of the rat beta-actin gene was determined. The gene codes for a protein identical to the bovine beta-actin. It has a large intron in the 5' untranslated region 6 nucleotides upstream from the initiator ATG, and 4 introns in the coding region at codons specifying amino acids 41/42, 121/122, 267, and 327/328. Unlike the skeletal muscle actin gene and many other actin genes, the beta-actin gene lacks the codon for Cys between the initiator ATG and the codon for the N-terminal amino acid of the mature protein. The usage of synonymous codons in the beta-actin gene is nonrandom, and is similar to that in the rat skeletal muscle and other vertebrate actin genes, but differs from the codon usage in yeast and soybean actin genes.

Actins↗
PubMedDate not supplied

Codon usage in Tetrahymena and other ciliates.

Codon usage in ciliates was examined by analyzing the coding regions of 22 ciliate genes corresponding to a total of 26,142 nucleotides (8,714 codons). It was found that Tetrahymena, Paramecium and the hypotrichs (Oxytricha and Stylonychia) differed in which synonymous codons were used most frequently by their genes. In fact, the codon choices in highly expressed Tetrahymena genes were more similar to those of yeast genes than those of Paramecium genes. The ciliates do not appear to have unusually strong biases in codon usage frequency when compared to other protists such as yeast. The analysis of the Tetrahymena genes indicated that genes which are highly expressed during normal cell growth have a stronger bias towards using the "preferred" codons than those expressed at lower levels during growth or for brief periods during processes such as conjugation. This conforms to what is found in other protists.

Amino Acids↗
PubMed1988

Why the rate of silent codon substitutions is variable within a vertebrate's genome.

Different genes within the murine genome are diverging at different rates. The rate of synonymous codon substitutions in these genes is related to their base composition. It is proposed that the variabilities of rate of mutation accumulation, of codon choice and of average GC content within vertebrate genomes are caused by differences between DNA synthesis in repair and replication, as far as the frequency and compositional bias of mutations introduced by these systems are concerned. DNA repair contributes substantially to the evolution of the DNA domains, which are actively repaired in germline cells and which correspond to regions available for transcription in these cells and to Giemsa-negative bands in stained chromosomes.

Animals↗
PubMed1982

Primary structure of the ompF gene that codes for a major outer membrane protein of Escherichia coli K-12.

The nucleotide sequence of the ompF gene coding for a major outer membrane protein of Escherichia coli K-12 has been determined and the amino acid sequence of the OmpF protein was deduced from it. The OmpF protein contains 340 amino acid residues, and is produced from a precursor having 22 extra amino acid residues, the signal peptide, at the amino terminus. The expected secondary structure of the OmpF protein had a high beta-sheet content with a low alpha-helix content. The promoter region and the transcription termination region of the ompF gene had a significantly high AT content, while the AT content of the coding region was about the same as the average AT content of the E. coli chromosome. Following the termination codon, a typical rho-independent transcription termination signal was observed. The codon usage in the ompF gene was highly nonrandom; the codons preferably utilized are those recognized by the most abundant species of isoaccepting tRNAs or those, among synonymous codons recognized by the same tRNA, that can interact more properly with the anticodon.

Amino Acid Sequence↗