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PubMed1992

Rates of mitochondrial DNA evolution in sharks are slow compared with mammals.

The rate of mitochondrial DNA (mtDNA) evolution has been carefully calibrated only in primates. Similarity between the primate calibration and rates estimated for other vertebrates has led to widespread assumption of a constant molecular clock in vertebrates even though this has never been rigorously tested. We report here the examination of mtDNA sequence variation for 13 species of sharks from two orders that are well represented in the fossil record to test the constancy hypothesis. Nucleotide substitution rates in the cytochrome b and cytochrome oxidase I genes in sharks are seven- to eightfold slower than in primates or ungulates. This difference in substitution rate cannot be explained by nucleotide composition bias, codon-usage bias, selection, or choice of genes sequenced, and was confirmed by comparing species recently separated by the rise of the Isthmus of Panama. Such differences in mtDNA substitution rates among taxa indicate that it is inappropriate to use a calibration for one group to estimate divergence times or demographic parameters for another group. High-resolution studies of molecular evolutionary rates require taxon-specific calibrations.

Animals↗
PubMed2001

Catalyzing bacterial speciation: correlating lateral transfer with genetic headroom.

Unlike crown eukaryotic species, microbial species are created by continual processes of gene loss and acquisition promoted by horizontal genetic transfer. The amounts of foreign DNA in bacterial genomes, and the rate at which this is acquired, are consistent with gene transfer as the primary catalyst for microbial differentiation. However, the rate of successful gene transfer varies among bacterial lineages. The heterogeneity in foreign DNA content is directly correlated with amount of genetic headroom intrinsic to a bacterial species. Genetic headroom reflects the amount of potentially dispensable information--reflected in codon usage bias and codon context bias--that can be transiently sacrificed to allow experimentation with functions introduced by gene transfer. In this way, genetic headroom offers a potential metric for assessing the propensity of a lineage to speciate.

Bacteria↗
PubMed2005

Analysis of synonymous codon usage in H5N1 virus and other influenza A viruses.

In this study, we calculated the codon usage bias in H5N1 virus and performed a comparative analysis of synonymous codon usage patterns in H5N1 virus, five other evolutionary related influenza A viruses and a influenza B virus. Codon usage bias in H5N1 genome is a little slight, which is mainly determined by the base compositions on the third codon position. By comparing synonymous codon usage patterns in different viruses, we observed that the codon usage pattern of H5N1 virus is similar with other influenza A viruses, but not influenza B virus, and the synonymous codon usage in influenza A virus genes is phylogenetically conservative, but not strain-specific. Synonymous codon usage in genes encoded by different influenza A viruses is genus conservative. Compositional constraints could explain most of the variation of synonymous codon usage among these virus genes, while gene function is also correlated to synonymous codon usages to a certain extent. However, translational selection and gene length have no effect on the variations of synonymous codon usage in these virus genes.

Base Composition↗
PubMedDate not supplied

Analysis of genomic G + C content, codon usage, initiator codon context and translation termination sites in Tetrahymena thermophila.

In recent years, the amount of molecular sequencing data from Tetrahymena thermophila has dramatically increased. We analyzed G + C content, codon usage, initiator codon context and stop codon sites in the extremely A + T rich genome of this ciliate. Average G + C content was 38% for protein coding regions, 21% for 5' non-coding sequences, 19% for 3' non-coding sequences, 15% for introns, 19% for micronuclear limited sequences and 17% for macronuclear retained sequences flanking micronuclear specific regions. The 75 available T. thermophila protein coding sequences favored codons ending in T and, where possible, avoided those with G in the third position. Highly expressed genes were relatively G + C-rich and exhibited an extremely biased pattern of codon usage while developmentally regulated genes were more A + T-rich and showed less codon usage bias. Regions immediately preceding Tetrahymena translation initiator codons were generally A-rich. For the 60 stop codons examined, the frequency of G in the end + 1 site was much higher than expected whereas C never occupied this position.

Animals↗
PubMed2003

Genomic background drives the divergence of duplicated amylase genes at synonymous sites in Drosophila.

In some Drosophila species, there are two types of greatly diverged amylase (Amy) genes (Amy clusters 1 and 2), each encoding active amylase isozymes. Cluster 1 is located at the middle of its chromosomal arm, and the region has a normal local recombination rate. However, cluster 2 is near the centromere, and this region is known to have a reduced recombination rate. Although nonsynonymous substitutions follow a molecular clock, synonymous substitutions were accelerated in cluster 2 after gene duplications. This resulted in a higher GC content at the third codon position (GC3) and codon usage bias in cluster 1, and lower GC3 content and codon usage bias in the cluster 2. However, no systematic difference in GC content was observed in the first and second codon positions or the 3'-flanking regions. Therefore, differences in local recombination rate rather than mutation bias might explain the divergence at synonymous sites between the two Amy clusters within species (Hill-Robertson effect). Alternatively, the different patterns and levels of expression between the two clusters may imply that the reduced expression level in cluster 2 caused by chromatin potentiation decreased the codon bias. Both of these hypotheses imply the importance of the genomic background as a driving force of divergence between non-tandemly duplicated genes.

3' Flanking Region↗
PubMed1998

Codon usage and gene function are related in sequences of Arabidopsis thaliana.

In this paper, the relationship between codon usage and the physiological pattern of expression of a gene is investigated while considering a dataset of 815 nuclear genes of Arabidopsis thaliana. Factorial Correspondence Analysis, a commonly used multivariate statistical approach in codon usage analysis, was used in order to analyse codon usage bias gene by gene. The analysis reveals a single major trend in codon usage among genes in Arabidopsis. At one end of the trend lie genes with a highly G/C biased codon usage. This group contains mainly photosynthetic and housekeeping genes which are known to encode the most abundant proteins of the vegetal cell. At the other extreme lie genes with a weaker A/T-biased codon usage. This group contain genes with various functions which exhibits most of the time a strong tissue-specific pattern of expression in relation, for example, to stress conditions. These observations were confirmed by the detailed analysis of codon usage in the multigene family of tubulins and appear to be general in plant species, even as distant from Arabidopsis thaliana as a monocotyledonous plant such as maize.

Arabidopsis↗
PubMed1999

Synonymous and nonsynonymous substitution rates in diatoms: a comparison between chloroplast and nuclear genes.

Rates of synonymous and nonsynonymous nucleotide substitutions and codon usage bias (ENC) were estimated for a number of nuclear and chloroplast genes in a sample of centric and pennate diatoms. The results suggest that DNA evolution has taken place, on an average, at a slower rate in the chloroplast genes than in the nuclear genes: a rate variation pattern similar to that observed in land plants. Synonymous substitution rates in the chloroplast genes show a negative association with the degree of codon usage bias, suggesting that genes with a higher degree of codon usage bias have evolved at a slower rate. While this relationship has been shown in both prokaryotes and multicellular eukaryotes, it has not been demonstrated before in diatoms.

Cell Nucleus↗
PubMed2003

A survey of codon and amino acid frequency bias in microbial genomes focusing on translational efficiency.

Unequal use of synonymous codons has been found in several prokaryotic and eukaryotic genomes. This bias has been associated with translational efficiency. The prevalence of this bias across lineages is currently unknown. Here, a new method (GCB) to measure codon usage bias is presented. It uses an iterative approach for the determination of codon scores and allows the computation of an index of codon bias suitable for interspecies comparison. A server to calculate GCB-values of individual genes as well as a list of compiled results are available at www.g21.bio.uni-goettingen.de. The method was applied to complete bacterial genomes. The relation of codon usage bias with amino acid composition and the choice of stop codons were determined and discussed.

Amino Acids↗
PubMed2006

Factors influencing synonymous codon and amino acid usage biases in Mimivirus.

Synonymous codon and amino acid usage biases have been investigated in 903 Mimivirus protein-coding genes in order to understand the architecture and evolution of Mimivirus genome. As expected for an AT-rich genome, third codon positions of the synonymous codons of Mimivirus carry mostly A or T bases. It was found that codon usage bias in Mimivirus genes is dictated both by mutational pressure and translational selection. Evidences show that four factors such as mean molecular weight (MMW), hydropathy, aromaticity and cysteine content are mostly responsible for the variation of amino acid usage in Mimivirus proteins. Based on our observation, we suggest that genes involved in translation, DNA repair, protein folding, etc., have been laterally transferred to Mimivirus a long ago from living organism and with time these genes acquire the codon usage pattern of other Mimivirus genes under selection pressure.

Amino Acids↗
PubMedDate not supplied

Cluster analysis of the codon use frequency of MHC genes from different species.

The relative synonymous codon use frequency of 135 MHC genes from four mammal species (Homo sapiens, Pan troglodyte, Macaca mulanta and Rattus norvegicus) is analyzed using a hierarchical cluster method. The result suggests that gene function is the dominant factor that determines codon usage bias, while species is a minor factor that determines further difference in codon usage bias for genes with similar functions. The conclusion may be useful in gene classification and gene function prediction.

Animals↗
PubMed2001

Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes.

Understanding the factors responsible for variations in mutation patterns and selection efficacy along chromosomes is a prerequisite for deciphering genome sequences. Population genetics models predict a positive correlation between the efficacy of selection at a given locus and the local rate of recombination because of Hill-Robertson effects. Codon usage is considered one of the most striking examples that support this prediction at the molecular level. In a wide range of species including Caenorhabditis elegans and Drosophila melanogaster, codon usage is essentially shaped by selection acting for translational efficiency. Codon usage bias correlates positively with recombination rate in Drosophila, apparently supporting the hypothesis that selection on codon usage is improved by recombination. Here we present an exhaustive analysis of codon usage in C. elegans and D. melanogaster complete genomes. We show that in both genomes there is a positive correlation between recombination rate and the frequency of optimal codons. However, we demonstrate that in both species, this effect is due to a mutational bias toward G and C bases in regions of high recombination rate, possibly as a direct consequence of the recombination process. The correlation between codon usage bias and recombination rate in these species appears to be essentially determined by recombination-dependent mutational patterns, rather than selective effects. This result highlights that it is necessary to take into account the mutagenic effect of recombination to understand the evolutionary role and impact of recombination.

Animals↗
PubMed2004

Analysis of factors shaping codon usage in the mitochondrion genome of Oryza sativa.

In this paper, the main factors shaping codon usage in the mitochondrion genome of rice were reported. Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The results showed that the main trend was strongly correlated with the gene expression level assessed by the 'Codon Adaptation Index' value, a result that was confirmed by the distribution of genes along the first axis. From the results that there were two significant correlations between axis 1 coordinates and the GC, GC3s content at silent sites of each sequence, and clearly significant correlations between the 'Effective Number of Codons' values and GC, GC3s content, we inferred that codon usage bias was affected by gene nucleotide composition also. In addition, the hydrophobicity of each protein also played some roles in shaping codon usage in this organelle, which could be confirmed by the significant correlation between the positions of genes placed on the first axis and the hydrophobicity value of each protein. In summary, natural selection played a crucial role, nucleotide mutational bias and amino acid composition only in a minor way, in shaping codon usage in the mitochondrion genome of rice. Notably, 21 codons defined firstly as 'optimal codons' might provide some more useful information for gene engineering and/or evolution studying.

Journal Article↗
PubMed2002

Influence of the leuX-encoded tRNA5(Leu) on the regulation of gene expression in pathogenic Escherichia coli.

The leuX gene encoding the minor tRNA5(Leu) is important for the expression of several virulence factors of pathogenic Escherichia coli strains. The differential usage of minor codons to control the expression of specialized genes has been proposed to be a general mechanism of bacteria to regulate gene expression at the posttranscriptional level. The minor codon usage theory foots on the biased codon usage of bacterial genes and the selective availability of tRNA isoacceptors. We aimed at the further investigation of the regulatory role of the tRNA5(Leu) for gene expression in pathogenic E. coli. For this purpose, the molecular mechanism underlying the tRNA5(Leu)-dependent regulation of different virulence-associated genes of pathogenic E. coli as well as the regulation of leuX transcription under various growth conditions were investigated in detail. The global impact of the presence or absence of the leuX-encoded tRNA on gene expression of the uropathogenic E. coli strain 536 was studied by proteome analysis. The obtained results argue for a general importance of the tRNA5(Leu) for gene expression of E. coli and the involvement of this tRNA in global regulatory networks.

Animals↗
PubMed1994

Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases.

Synonymous codon usage varies considerably among Caenorhabditis elegans genes. Multivariate statistical analyses reveal a single major trend among genes. At one end of the trend lie genes with relatively unbiased codon usage. These genes appear to be lowly expressed, and their patterns of codon usage are consistent with mutational biases influenced by the neighbouring nucleotide. At the other extreme lie genes with extremely biased codon usage. These genes appear to be highly expressed, and their codon usage seems to have been shaped by selection favouring a limited number of translationally optimal codons. Thus, the frequency of these optimal codons in a gene appears to be correlated with the level of gene expression, and may be a useful indicator in the case of genes (or open reading frames) whose expression levels (or even function) are unknown. A second, relatively minor trend among genes is correlated with the frequency of G at synonymously variable sites. It is not yet clear whether this trend reflects variation in base composition (or mutational biases) among regions of the C.elegans genome, or some other factor. Sequence divergence between C.elegans and C.briggsae has also been studied.

Animals↗
PubMed1995

Phylogeny, rates of evolution, and patterns of codon usage among sea urchin retroviral-like elements, with implications for the recognition of horizontal transfer.

Phylogenetic relationships, rates of evolution, and codon usage were investigated in a family of retrotransposons (SURL elements) found in echinoids. The phylogeny of SURL element reverse transcriptase sequences from 10 echinoid species clearly shows the phylogenetic signature of the host taxa as well as paralogous sequences that diverged prior to speciation events. Two subfamilies (1 and 5) of SURL element reverse transcriptase sequences are recognized that diverged prior to the radiation of the Echinometridae. Comparisons of synonymous versus nonsynonymous substitutions indicate that SURL elements have been active in echinoid genomes and have evolved under purifying selection for millions of years. Rates of synonymous substitution for reverse transcriptase are similar to rates of single-copy DNA evolution and to rates of synonymous substitution for the H3 and H4 histone genes, contradicting the assumption that rates of evolution are accelerated in retrotransposons. Finally, codon usage in SURL elements is biased for codons ending in A or U relative to 42 sea urchin nuclear genes. Biased codon usage is sometimes cited as evidence for horizontal transfer, but in the case of SURL elements this bias occurs in spite of a long history of vertical transmission rather than because of horizontal transfer.

Animals↗
PubMed2003

Strand compositional asymmetries of nuclear DNA in eukaryotes.

Both DNA replication and transcription are structurally asymmetric processes. An asymmetric nucleotide substitution pattern has been observed between the leading and the lagging strand, and between the coding and the noncoding strand, in eubacterial, viral, and organelle genomes. Similar studies in eukaryotes have been rare, because the origins of replication in nuclear genomes are mostly unknown and the replicons are much shorter than those of prokaryotes. To circumvent these predicaments, all possible pairs of neighboring genes that are located on different strands of nuclear DNA were selected from the complete genomes of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Plasmodium falciparum, Encephalitozoon cuniculi, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Anopheles gambiae, Mus musculus, and Homo sapiens. For such a pair of genes, one is likely coded from the leading strand and the other from the lagging strand. By examining the introns and the fourfold degenerate sites of codons in the genes of each pair, we found that the relative frequencies of T vs. A and of G vs. C are significantly skewed in most eukaryotes studied. In a gene pair, the potential effects of replication- and transcription-associated mutation bias on strand asymmetry are in the same direction for one gene where leading strand synthesis shares the same template with transcription, while they tend to be canceled out in the other gene. Our study demonstrates that DNA replication-associated and transcription-associated mutation bias and/or selective codon usage bias may affect the strand nucleotide composition asymmetrically in eukaryotic genomes.

Animals↗
PubMed2026

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↗
PubMed2001

Synonymous codon usage, accuracy of translation, and gene length in Caenorhabditis elegans.

In many unicellular organisms, invertebrates, and plants, synonymous codon usage biases result from a coadaptation between codon usage and tRNAs abundance to optimize the efficiency of protein synthesis. However, it remains unclear whether natural selection acts at the level of the speed or the accuracy of mRNAs translation. Here we show that codon usage can improve the fidelity of protein synthesis in multicellular species. As predicted by the model of selection for translational accuracy, we find that the frequency of codons optimal for translation is significantly higher at codons encoding for conserved amino acids than at codons encoding for nonconserved amino acids in 548 genes compared between Caenorhabditis elegans and Homo sapiens. Although this model predicts that codon bias correlates positively with gene length, a negative correlation between codon bias and gene length has been observed in eukaryotes. This suggests that selection for fidelity of protein synthesis is not the main factor responsible for codon biases. The relationship between codon bias and gene length remains unexplained. Exploring the differences in gene expression process in eukaryotes and prokaryotes should provide new insights to understand this key question of codon usage.

Animals↗