[Synonymous codon usage at the ends of double-stranded regions in the secondary structure of mRNA].
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Bacteriophages↗
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Codon usage tabulated from the GenBank genetic sequence data.
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Animals↗
Codon usage tabulated from the GenBank genetic sequence data.
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Amino Acids↗
Translation rate modification by preferential codon usage: intragenic position effects.
We present a model for calculating the protein production rate as a function of the translation rate. The model takes into account that the elongation rate along an mRNA molecule is non-uniform as a result of different tRNA availabilities for different codons. Initiation of ribosomes on an mRNA is normally the rate-limiting step in the translation process, and blocking of the initiation site can be avoided if the codons closest to this site allow fast translation by the ribosome. Hence, different selective forces may act on the choice of synonymous codons in the initiation region than elsewhere on a given mRNA. We show that the elongation rate along the whole mRNA influences the production rate of abundant proteins, whereas only the elongation rate in the initiation region is of importance for the production rate of rare proteins. We also present an analysis of the codon distribution along known mRNAs coding for abundant and rare proteins.
Bacterial Proteins↗
Preliminary indication of unusual codon usage in the DNA coding sequence of the attachment protein of Mycoplasma pneumoniae.
From a Mycoplasma pneumoniae genomic library, three recombinant clones encoding approximately one-third of the attachment (P1) gene were identified. P1 fusion proteins expressed by these clones in Escherichia coli were found to be much smaller than expected from the sizes of the cloned DNA fragments. Nucleotide sequence analysis revealed the presence of UGA codons in the open reading frames of two of the clones, explaining the incomplete translation of the inserts. Sequencing data further revealed that two of the recombinant clones did have similar but not identical carboxyl-end sequences. This finding suggests the existence of more than one genomic DNA sequence coding for the 3'-end of the P1 gene. Potential transcriptional regulatory sequences, a possible termination signal at the 3'-end of the P1 gene and possible promoter-like structures, have been recognized.
Amino Acid Sequence↗
Strong homology between the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase of two species of Acetabularia and the occurrence of unusual codon usage.
Amino acid sequences of the small subunit of ribulose-1,5-bisphosphate carboxylase (SSU) of Acetabularia cliftonii and A. mediterranea were derived from five cDNA sequences of each of the two species of algae and by direct amino acid sequence determination of the isolated protein. An homology of more than 96% between the proteins indicates the close relationship between the two algae. All ten cDNAs in the reading frame display the termination codons TAA and/or TAG at various positions, which seem to code for the amino acid glutamine when compared with the amino acid sequence from the mature protein. This is reminiscent of proteins from ciliates where TAA and TAG also code for glutamine.
Acetabularia↗
Efficient synthesis of secreted murine interleukin-2 by Saccharomyces cerevisiae: influence of 3'-untranslated regions and codon usage.
Several expression vectors were compared which directed the synthesis of secreted murine interleukin-2 (mIL2) in the culture medium of Saccharomyces cerevisiae. We used the prepro-sequence of the alpha 1 mating-factor precursor as a secretion signal in S. cerevisiae in combination with different promoters. The yield of mature mIL2 was significantly improved by deleting the major part of the 3'-untranslated region (UTR). In Northern-blotting experiments we showed that a destabilizing sequence present in the 3' UTR might be responsible for rapid degradation of the mIL2 mRNA. The highest expression (about 10 micrograms/ml) was obtained under control of the GAL1 promoter in an S. cerevisiae strain where the regulatory GAL4 gene was overexpressed. No difference in expression level was observed in a construct wherein twelve consecutive codons were replaced by optimal codons for S. cerevisiae.
Animals↗
Codon usage and mistranslation. In vivo basal level misreading of the MS2 coat protein message.
The coat protein of the small RNA virus MS2 shows charge heterogeneity in vivo. In most strains there is a basic satellite of the native protein. We have shown that this basic satellite is greatly diminished or absent in strains with the streptomycin-resistant allele, rpsL, a mutation which leads to increased translational accuracy. Further, the satellite is present in cells where the coat protein is encoded by duplex DNA. Tryptic digests of the satellite show that it contains new lysine-containing peptides which appear to be the same as those found in derivatives of coat protein which have a lysine for asparagine substitution. Sequencing of the NH2-terminal 19 amino acids of the satellite protein shows that the asparagine codon AAU at amino acid 12 is misread approximately 8 times more frequently than the AAC at amino acid 3. We conclude that the satellite species is the result of basal level lysine for asparagine substitution. These substitutions are most likely caused by preferential misreading of AAU codons at a frequency of approximately 5 X 10(-3), 10-fold higher than the average error frequency.
Amino Acid Sequence↗
Co-evolution of base composition and codon usage in Xenopus laevis and human globin genes with long-range DNA organization of their genome.
Eucaryotic DNA is punctuated by many A+T-rich segments that we named A+T-rich linkers. Two types of these A+T-rich linkers can be distinguished: (i) isolated A+T-rich linkers, and (ii) A+T-rich linkers crowded in clusters. We have analysed the distribution of A+T-rich linker across the alpha- and beta-globin gene domain in Xenopus laevis and human genomes using isodenaturation and electron microscopy. Comparison of our data with those previously obtained for the avian globin genes leads us to conclude that genes can be harboured indifferently in either domain. A correlation is established between the presence of A+T-rich linker inside introns and flanking regions and the A+T content of the coding sequence. For the coding sequence, a high A+T content is strongly correlated with high A+T content in the codon's third position and weakly in the first position.
Animals↗
Codon usage and secondary structure of MS2 phage RNA.
MS2 is an RNA bacteriophage (3569 bases). The secondary structure of the RNA has been determined, and is known to play an important role in regulating translation. Paired regions of the genome have a higher G+C content than unpaired regions. It has been suggested that this reflects selection for high G+C content to encourage pairing, but a re-analysis of the data together with computer simulation suggest that it is an automatic consequence in any RNA sequence of the way it folds up to minimise its free energy. It has also been suggested that the three registers in which pairing can occur in a coding region are used differentially to optimise the use of the redundancy of the genetic code, but re-analysis of the data shows only weak statistical support for this hypothesis.
Base Composition↗
Codon usage table for Xenopus laevis.
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Animals↗
Models of nearly neutral mutations with particular implications for nonrandom usage of synonymous codons.
The population dynamics of nearly neutral mutations are studied using a single-site and a multisite model. In the latter model, the nucleotides in a sequence are completely linked and the selection schemes employed are additive, multiplicative, and additive with a threshold. Although the third selection scheme is very different from the first two, the three schemes produce identical results for a wide range of parameter values. Thus the present study provides a general theory for the population dynamics of nearly neutral mutations because the results can also be used to draw inferences about other selection schemes such as stabilizing selection and synergistic selection. It is shown that the number of slightly deleterious mutations accumulated in a sequence can be considerably larger under the multisite model than under the single-site model, particularly if the sequence is long or if the mutation rate per site is high. The results show that even a very slight selective difference between synonymous codons can produce a strong bias in codon usage. Three alternative explanations for the strong bias in codon usage in bacterial and yeast genes are considered. The implications of the present results for molecular evolution are discussed.
Biological Evolution↗
The 'effective number of codons' used in a gene.
A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request.
Animals↗
Stable structure of thermophilic proton ATPase beta subunit.
F1-ATPase is the major enzyme for ATP synthesis in mitochondria, chloroplasts, and bacterial plasma membranes. F1-ATPase obtained from thermophilic bacterium PS3 (TF1) is the only ATPase which can be reconstituted from its primary structure. Its beta subunit constitutes the catalytic site, and is capable of forming hybrid F1's with E. coli alpha and gamma subunits. Since the stability of TF1 resides in its primary structure, we cloned a gene coding for TF1, and the primary structure of the beta subunit was deduced from the nucleotide sequence of the gene to compare the sequence with those of beta's of three major categories of F1's; prokaryotic membranes, chloroplasts, and mitochondria. The following results were obtained. Homology: The primary structure of the TF1 beta subunit (473 residues, Mr = 51,995.6) showed 89.3% homology with 270 residues which are identical in the beta subunits from human mitochondria, spinach chloroplasts, and E. coli. It contained regions homologous to several nucleotide-binding proteins. Secondary structure: The deduced alpha-helical (30.1%) and beta-sheet (22.3%) contents were consistent with those determined from the circular dichroism spectra. Residues forming reverse turns (Gly and Pro) were highly conserved among the F1 beta subunits. Substituted residues and stability of TF1: We compared the amino acid sequence of the TF1 beta subunit with those of the other F1 beta subunits mentioned above. The observed substitutions in the thermophilic subunit increased its propensities to form secondary structures, and its external polarity to form tertiary structure. Codon usage: The codon usage of the TF1 beta gene was found to be unique. The changes in codons that achieved these amino acid substitutions were much larger than those caused by minimal mutations, and the third letters of the optimal codons were either guanine or cytosine, except in codons for Gln, Lys, and Glu.
Amino Acid Sequence↗
Unusual codon bias occurring within insertion sequences in Escherichia coli.
The large open reading frames of insertion sequences from Escherichia coli were examined for their spatial pattern of codon usage bias and distribution of rarely used codons. There is a bias in codon usage that is generally lower toward the terminal ends of the coding regions, which is reflected in the occurrence of an excess of nonpreferred codons in the 3' portions of the coding regions as compared with the 5' portions. In contrast, typical chromosomal genes have a lower codon usage bias toward the 5' ends of the coding regions. These results imply that the selective forces reflected in codon usage bias may differ according to position within the coding sequence. In addition, these constraints apparently differ in important ways between genes contained in insertion sequences and those in the chromosome.
Chromosomes, Bacterial↗
De Novo Assembly and Comparative Analysis of the Complete Mitochondrial Genome of Mesenchytraeus (Annelida, Enchytraeidae).
The Changbai Mountain range is one of the key glacial refugia in Northeast Asia. Mesenchytraeus exhibits high species diversity, strong endemism, and widespread cryptic species in this region, for which mitogenomes provide useful molecular markers for exploring cryptic species complexes. This makes Mesenchytraeus an ideal model for studying mitogenome evolution among closely related lineages; however, no mitogenome data have been reported for this genus to date. In this study, we performed de novo assembly, annotation, and comparative analysis of the mitogenomes of 13 Mesenchytraeus species (14 individuals) from Changbai Mountain. All mitogenomes are typical circular molecules containing 37 genes, but putative control regions are rearranged and consistently located between ATP6 and trnR. All species exhibit annelid-specific strand nucleotide biases, characterized by negative GC skew and near-zero AT skew. Codon usage analysis reveals that codon families with wobble U are significantly biased toward mtDNA codons, whereas those with wobble C or G are biased toward non-mtDNA codons, suggesting a conserved mitochondrial codon usage pattern in annelids. All tRNAs form typical cloverleaf secondary structures except trnS2, which lacks the D-stem and the dihydrouridine (DHU) arm in some species. The putative control regions commonly contain complex palindromic repeats, hairpins, and repetitive elements, and may harbor dual replication origins. Phylogenetic analyses support the monophyly of Mesenchytraeus and reveal significant molecular divergence among morphologically cryptic species. This study provides the first mitogenome dataset for Mesenchytraeus and offers new insights into the evolution and replication mechanisms of mitogenomes in Clitellata and broader Annelida.
Mesenchytraeus↗
Usage of the three termination codons: compilation and analysis of the known eukaryotic and prokaryotic translation termination sequences.
The published translation termination sequences have been compiled and analysed to aid the interpretation of experiments on termination codon usage in the Xenopus oocyte (Bienz et al. 1981). There are significant differences between prokaryotes and eukaryotes concerning the usage of the three termination codons and of tandem stops. In addition viruses show termination strategies that differ from those of their hosts. Preferred context sequences flanking termination codons are described. Contexts vary within the last codon according to the nature of the termination codon, but are uniform within the first triplet following the terminators.
Animals↗
Multilayered nucleotide organization reveals purifying selection and host-driven adaptation in CPV and FPV.
Since feline panleukopenia virus (FPV) is considered the most likely ancestor of canine parvovirus (CPV), comprehensive comparisons of nucleotide organization in corresponding viral genes between CPV and FPV may provide novel insights into the evolutionary dynamics underlying the divergence of these two viruses. Here, we characterize the evolutionary patterns of CPV and FPV genes across multiple levels of nucleotide organization. Both viruses exhibited highly conserved nucleotide usage at nonsynonymous sites, with Ka/Ks patterns consistent with strong purifying selection, whereas synonymous sites showed greater variability. CpG dinucleotides were markedly underrepresented across all four viral genes, suggesting host-associated selective pressure and/or intrinsic nucleotide compositional constraints. Extensive nonrandom biases in synonymous codon usage, codon neighboring nucleotide context, and codon pair usage further revealed fine-scale genomic optimization shaped by natural selection and nucleotide compositional constraints. Structural protein genes (VP1 and VP2) displayed stronger codon usage bias and higher tRNA adaptation than nonstructural genes. Moreover, CPV genes showed greater translational adaptation to feline hosts than to canine hosts. These findings highlight how closely related parvoviruses exploit flexible nucleotide organization to facilitate host adaptation while maintaining essential protein functions.
Animals↗