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PubMed2003

Factors affecting codon usage in Yersinia pestis.

The complete genome of Yersinia pestis which was the causative agent of the systemic invasive infectious disease classically referred as plague, had been recently sequenced. In order to have a further insight into the synonymous codon usage evolution, factors shaping synonymous codon usage pattern of Yersinia pestis were analyzed in this paper. The coding sequences larger than or equal to 300 bp were used in codon usage analysis. Though "G"+"C" content in Y. pestis genome was slightly lower (47.64%), the highly expressed genes tended to use "C" or "G" at synonymous sites compared with lowly expressed genes. Conversely, lowly expressed genes tended to prefer "A" or "T" at synonymous positions. Gene expression level was strongly correlated with the first axis of the correspondence analysis (COA) (R=0.63, P<0.0001). By the analyses of the codon usage pattern of highly and lowly expressed genes, it was confirmed that gene expression level was partially responsible for the codon usage bias. GC-skew analysis showed that codon usage suffered replication-transcriptional selection. Codon adaptation index (CAI), frequency of "C"+"G" at the synonymous third position of codon (GC3s) and the effective number of codons (Nc) values showed some differences among different gene length groups. "G"+"C" content of genes was strongly correlated with the first axis of the COA (R=0.72, P<0.0001). It could be concluded that gene expressivity, replication-transcriptional selection, gene length and gene composition constraints were the main affecting factors of codon usage variation in Y. pestis.

Amino Acids↗
PubMed2004

A systematic method to identify genomic islands and its applications in analyzing the genomes of Corynebacterium glutamicum and Vibrio vulnificus CMCP6 chromosome I.

MOTIVATION: Some genomic islands contain horizontally transferred genes, which play critical roles in altering the genotypes and phenotypes of organisms, and horizontal gene transfer has been recognized as a universal event throughout bacterial evolution. A windowless method to display the distribution of genomic GC content, the cumulative GC profile, is proposed to identify genomic islands in genomes whose complete genome sequences are available. Two new indices are proposed to assess the codon usage bias and amino acid usage bias in genomic islands. RESULTS: A 211 kb genomic island (CGGI-1) has been identified in the genome of Corynebacterium glutamicum, and three genomic islands VVGI-1, VVGI-2 and VVGI-3, with lengths 167, 40 and 33 kb, respectively, have been identified in the genome of Vibrio vulnificus CMCP6 chromosome I. The CGGI-1 is flanked by two approximately 500 bp direct repeats, and utilizes a Val-tRNA as the integration site. For the VVGI-1 and VVGI-2, each has an integrase gene at 5' junction. All the identified genomic islands show unusual GC content, codon usage and amino acid usage, compared with the rest of the genomes. In addition, it is found that genomic islands are fairly homogenous in terms of GC content variation. An index, h, to quantify the homogeneity of GC content for genomic islands is proposed, and it is shown that h is less than 0.1 for all the genomic islands analyzed. The cumulative GC profile, as well as various indices to assess the codon usage bias, amino acid usage bias and homogeneity of the genomic islands, will be useful in the analysis of other genomes. AVAILABILITY: Programs used in this work and numerical results are available upon request.

Algorithms↗
PubMed2002

DNA thermodynamic pressure: a potential contributor to genome evolution.

Codon usage bias is a feature of living organisms. The origin of this bias might be explained not only by external factors but also by the nature of the structure of deoxyribonucleic acid (DNA) itself. We have developed a point mutation simulation program of coding sequences, in which nucleotide replacement follows thermodynamic criteria. For this purpose we calculated the hydrogen bond-like and electrostatic energies of non-canonical base pairs in a 5 bp neighbourhood. Although the rate of non-canonical base pair formation is extremely low, such pairs occur with a preference towards a guanine (G) or cytosine (C) rather than an adenine (A) or thymine (T) replacement due to thermodynamic considerations. This feature, according to the simulation program, should result in an increase in the GC content of the genome over evolutionary time. In addition, codon bias towards a higher GC usage is also predicted. DNA sequence analysis of genes of the Trypanosomatidae lineage supported the hypothesis that DNA thermodynamic pressure is a driving force that impels increases in GC content and GC codon bias.

Algorithms↗
PubMed2000

Studies on codon usage in Entamoeba histolytica.

Codon usage bias of Entamoeba histolytica, a protozoan parasite, was investigated using the available DNA sequence data. Entamoeba histolytica having AT rich genome, is expected to have A and/or T at the third position of codons. Overall codon usage data analysis indicates that A and/or T ending codons are strongly biased in the coding region of this organism. However, multivariate statistical analysis suggests that there is a single major trend in codon usage variation among the genes. The genes which are supposed to be highly expressed are clustered at one end, while the majority of the putatively lowly expressed genes are clustered at the other end. The codon usage pattern is distinctly different in these two sets of genes. C ending codons are significantly higher in the putatively highly expressed genes suggesting that C ending codons are translationally optimal in this organism. In the putatively lowly expressed genes A and/or T ending codons are predominant, which suggests that compositional constraints are playing the major role in shaping codon usage variation among the lowly expressed genes. These results suggest that both mutational bias and translational selection are operational in the codon usage variation in this organism.

Animals↗
PubMed2004

Codon usage and bias in mitochondrial genomes of parasitic platyhelminthes.

Sequences of the complete protein-coding portions of the mitochondrial (mt) genome were analysed for 6 species of cestodes (including hydatid tapeworms and the pork tapeworm) and 5 species of trematodes (blood flukes and liver- and lung-flukes). A near-complete sequence was also available for an additional trematode (the blood fluke Schistosoma malayensis). All of these parasites belong to a large flatworm taxon named the Neodermata. Considerable variation was found in the base composition of the protein-coding genes among these neodermatans. This variation was reflected in statistically-significant differences in numbers of each inferred amino acid between many pairs of species. Both convergence and divergence in nucleotide, and hence amino acid, composition was noted among groups within the Neodermata. Considerable variation in skew (unequal representation of complementary bases on the same strand) was found among the species studied. A pattern is thus emerging of diversity in the mt genome in neodermatans that may cast light on evolution of mt genomes generally.

Amino Acid Sequence↗
PubMed1994

Divergence in codon usage of Lactobacillus species.

We have analyzed codon usage patterns of 70 sequenced genes from different Lactobacillus species. Codon usage in lactobacilli is highly biased. Both inter-species and intra-species heterogeneity of codon usage bias was observed. Codon usage in L. acidophilus is similar to that in L. helveticus, but dissimilar to that in L. bulgaricus, L. casei, L. pentosus and L. plantarum. Codon usage in the latter three organisms is not significantly different, but is different from that in L. bulgaricus. Inter-species differences in codon usage can, at least in part, be explained by differences in mutational drift. L. bulgaricus shows GC drift, whereas all other species show AT drift. L. acidophilus and L. helveticus rarely use NNG in family-box (a set of synonymous) codons, in contrast to all other species. This result may be explained by assuming that L. acidophilus and L. helveticus, but not other species examined, use a single tRNA species for translation of family-box codons. Differences in expression level of genes are positively correlated with codon usage bias. Highly expressed genes show highly biased codon usage, whereas weakly expressed genes show much less biased codon usage. Codon usage patterns at the 5'-end of Lactobacillus genes is not significantly different from that of entire genes. The GC content of codons 2-6 is significantly reduced compared with that of the remainder of the gene. The possible implications of a reduced GC content for the control of translation efficiency are discussed.

Base Sequence↗
PubMed1995

Intrastrand parity rules of DNA base composition and usage biases of synonymous codons.

When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2). Significant deviations from the parity rules in the third codon letters of the four-codon amino acids result mostly from selective biases rather than mutational biases between the two strands of DNA during evolution. The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance. The present analysis shows that, although the PR2 violation is common in the third codon letters of four-codon amino acids, the contribution of PR2 violation to the DNA G + C content of the third codon position is small and, in majority of cases, mildly counteracts the effect of the directional mutation pressure on the G + C content.

Animals↗
PubMed1994

Selection on silent sites in the rodent H3 histone gene family.

Selection promoting differential use of synonymous codons has been shown for several unicellular organisms and for Drosophila, but not for mammals. Selection coefficients operating on synonymous codons are likely to be extremely small, so that a very large effective population size is required for selection to overcome the effects of drift. In mammals, codon-usage bias is believed to be determined exclusively by mutation pressure, with differences between genes due to large-scale variation in base composition around the genome. The replication-dependent histone genes are expressed at extremely high levels during periods of DNA synthesis, and thus are among the most likely mammalian genes to be affected by selection on synonymous codon usage. We suggest that the extremely biased pattern of codon usage in the H3 genes is determined in part by selection. Silent site G + C content is much higher than expected based on flanking sequence G + C content, compared to other rodent genes with similar silent site base composition but lower levels of expression. Dinucleotide-mediated mutation bias does affect codon usage, but the affect is limited to the choice between G and C in some fourfold degenerate codons. Gene conversion between the two clusters of histone genes has not been an important force in the evolution of the H3 genes, but gene conversion appears to have had some effect within the cluster on chromosome 13.

Animals↗
PubMed1999

The nonrandom location of synonymous codons suggests that reading frame-independent forces have patterned codon preferences.

Biased codon usage is common in eukaryotic and prokaryotic genes. Evidence from Escherichia, Saccharomyces, and Drosophila indicates that it favors translational efficiency and accuracy. However, to date no functional advantages have been identified in the codon-anticodon interactions involving the most frequently used (preferred) codons. Here we present evidence that forces not related to the individual codon-anticodon interaction may be involved in determining which synonymous codons are preferred or avoided. We show that the "off-frame" trinucleotide motif preferences inferrable from Drosophila coding regions are often in the same direction as Drosophila's "in-frame" codon preferences, i.e., its codon usage. The off-frame preferences were inferred from the nonrandomness of the location of confamilial synonymous codons along coding regions-a pattern often described as a context dependence of nucleotide choice at synonymous positions or as codon-pair bias. We relied on randomizations of the location of confamilial codons that do not alter, and cannot be influenced by, the encoded amino acid sequences, codon usage, or base composition of the genes examined. The statistically significant congruency of in-frame and off-frame trinucleotide preferences suggests that the same kind of reading-frame-independent force(s) may also influence synonymous codon choice. These forces may have produced biases in codon usage that then led to the evolution of the translational advantages of these motifs as preferred codons. Under this scenario, tRNA pool size differences between preferred and nonpreferred codons initially were evolved to track the default overrepresentation of codons with preferred motifs. The motif preference hypothesis can explain the structuring of codon preferences and the similarities in the codon usages of distantly related organisms.

Amino Acid Sequence↗
PubMed2003

Evolution of the GC content of the histone 3 gene in seven Drosophila species.

The molecular evolution of the histone multigene family was studied by cloning and determining the nucleotide sequences of the histone 3 genes in seven Drosophila species, D. takahashii, D. lutescens, D. ficusphila, D. persimilis, D.pseudoobscura, D. americana and D. immigrans. CT repeats, a TATA box and an AGTG motif in the 5' region, and a hairpin loop and purine-rich motifs (CAA(T/G)GAGA) in the 3' region were conserved even in distantly related species. In D. hydei and D.americana, the GC content at the third codon position in the protein coding region was relatively low (49% and 45%), while in D. takahashii and D. lutescens it was relatively high (64% and 65%). The non- significant correlation between the GC contents in the 3' region and at the third codon position as well as the evidence of less constraint in the 3' region suggested that mutational bias may not be the major mechanism responsible for the biased nucleotide change at the third codon position or for codon usage bias.

Animals↗
PubMed1984

A method for measuring the non-random bias of a codon usage table.

We describe a new statistical method for measuring bias in the codon usage table of a gene. The test is based on the multinomial and Poisson distributions. The method is used to scan DNA sequences and measure the strength of codon preference. For E. Coli we show that the strength of codon preference is related to levels of gene expression. The method can also be used to compare base triplet frequencies with those expected from the base composition. This second type of codon bias test is useful for distinguishing coding from non-coding regions.

Base Sequence↗
PubMed1996

Molecular evolution of ependymin and the phylogenetic resolution of early divergences among euteleost fishes.

The rate and pattern of DNA evolution of ependymin, a single-copy gene coding for a highly expressed glycoprotein in the brain matrix of teleost fishes, is characterized and its phylogenetic utility for fish systematics is assessed. DNA sequences were determined from catfish, electric fish, and characiforms and compared with published ependymin sequences from cyprinids, salmon, pike, and herring. Among these groups, ependymin amino acid sequences were highly divergent (up to 60% sequence difference), but had surprisingly similar hydropathy profiles and invariant glycosylation sites, suggesting that functional properties of the proteins are conserved. Comparison of base composition at third codon positions and introns revealed AT-rich introns and GC-rich third codon positions, suggesting that the biased codon usage observed might not be due to mutational bias. Phylogenetic information content of third codon positions was surprisingly high and sufficient to recover the most basal nodes of the tree, in spite of the observation that pairwise distances (at third codon positions) were well above the presumed saturation level. This finding can be explained by the high proportion of phylogenetically informative nonsynonymous changes at third codon positions among these highly divergent proteins. Ependymin DNA sequences have established the first molecular evidence for the monophyly of a group containing salmonids and esociforms. In addition, ependymin suggests a sister group relationship of electric fish (Gymnotiformes) and Characiformes, constituting a significant departure from currently accepted classifications. However, relationships among characiform lineages were not completely resolved by ependymin sequences in spite of seemingly appropriate levels of variation among taxa and considerably low levels of homoplasy in the data (consistency index = 0.7). If the diversification of Characiformes took place in an "explosive" manner, over a relatively short period of time this pattern should also be observed using other phylogenetic markers. Poor conservation of ependymin's primary structure hinders the design of efficient primers for PCR that could be used in wide-ranging fish systematic studies. However, alternative methods like PCR amplification from cDNA used here should provide promising comparative sequence data for the resolution of phylogenetic relationships among other basal lineages of teleost fishes.

Amino Acid Sequence↗
PubMed1988

Characterization of catalase transcripts and their differential expression in maize.

In maize, the three unlinked catalase (EC 1.11.1.6) structural genes (Cat1, Cat2 and Cat3) are differentially expressed temporally, spatially and in response to environmental signals in the developing seedling. In order to understand more fully the molecular mechanisms involved in catalase gene expression, full-length cDNA clones representing the maize Cat1, Cat2 and Cat3 transcripts were isolated and characterized. DNA sequence analysis confirmed that each cDNA encodes a unique catalase protein. Gene-specific probes for the three maize catalase cDNAs were isolated and used to probe blots of poly(A)+ RNA isolated from various maize tissues. Cat1 mRNA was found in scutella, milky endosperm of immature kernels, leaves and epicotyls. The Cat2 mRNA was present primarily in post-germinative scutella, with lower levels in leaves and epicotyls. Cat3 mRNA was detected primarily in epicotyls and, to a lesser extent, in leaves and scutella. The gene-specific probes hybridized with maize genomic DNA blots in simple, but unique patterns, indicating that there is one, or a very few copies of each catalase gene. The coding region of the Cat3 cDNA comprised 66% G + C, which led to a strong codon usage bias in this gene. This codon bias was also seen with the Cat2 transcripts, but not with those for Cat1. A high degree of similarity was found between the maize catalase nucleic acid and deduced amino-acid sequences and those of sweet potato and rat liver catalase.

Amino Acid Sequence↗
PubMed2006

The evolution of biased codon and amino acid usage in nematode genomes.

Despite the degeneracy of the genetic code, whereby different codons encode the same amino acid, alternative codons and amino acids are utilized nonrandomly within and between genomes. Such biases in codon and amino acid usage have been demonstrated extensively in prokaryote genomes and likely reflect a balance between the action of mutation, selection, and genetic drift. Here, we quantify the effects of selection and mutation drift as causes of codon and amino acid-usage bias in a large collection of nematode partial genomes from 37 species spanning approximately 700 Myr of evolution, as inferred from expressed sequence tag (EST) measures of gene expression and from base composition variation. Average G + C content at silent sites among these taxa ranges from 10% to 63%, and EST counts range more than 100-fold, underlying marked differences between the identities of major codons and optimal codons for a given species as well as influencing patterns of amino acid abundance among taxa. Few species in our sample demonstrate a dominant role of selection in shaping intragenomic codon-usage biases, and these are principally free living rather than parasitic nematodes. This suggests that deviations in effective population size among species, with small effective sizes among parasites, are partly responsible for species differences in the extent to which selection shapes patterns of codon usage. Nevertheless, a consensus set of optimal codons emerges that is common to most taxa, indicating that, with some notable exceptions, selection for translational efficiency and accuracy favors similar sets of codons regardless of the major codon-usage trends defined by base compositional properties of individual nematode genomes.

Amino Acids↗
PubMed2002

Codon usage by transposable elements and their host genes in five species.

We compared the codon usage of sequences of transposable elements (TEs) with that of host genes from the species Drosophila melanogaster, Arabidopsis thaliana, Caenorhabditis elegans, Saccharomyces cerevisiae, and Homo sapiens. Factorial correspondence analysis showed that, regardless of the base composition of the genome, the TEs differed from the genes of their host species by their AT-richness. In all species, the percentage of A + T on the third codon position of the TEs was higher than that on the first codon position and lower than that in the noncoding DNA of the genomes. This indicates that the codon choice is not simply the outcome of mutational bias but is also subject to selection constraints. A tendency toward higher A + T on the third position than on the first position was also found in the host genes of A. thaliana, C. elegans, and S. cerevisiae but not in those of D. melanogaster and H. sapiens. This strongly suggests that the AT choice is a host-independent characteristic common to all TEs. The codon usage of TEs generally appeared to be different from the mean of the host genes. In the AT-rich genomes of Arabidopsis thaliana, Caenorhabditis elegans, and Saccharomyces cerevisiae, the codon usage bias of TEs was similar to that of weakly expressed genes. In the GC-rich genome of D. melanogaster, however, the bias in codon usage of the TEs clearly differed from that of weakly expressed genes. These findings suggest that selection acts on TEs and that TEs may display specific behavior within the host genomes.

Animals↗
PubMed1992

Characterization of a highly expressed lignin peroxidase-encoding gene from the basidiomycete Phanerochaete chrysosporium.

The genomic clone, LG2, encoding LiP2, the major lignin peroxidase (LiP) isozyme from Phanerochaete chrysosporium strain OGC101, was isolated and characterized. The 5'-untranslated region of LG2 contains sequences similar to CRE and XRE promoter elements. Comparison with its transcript indicates that eight introns, each less than 59 bp, interrupt the coding sequence. Comparison with genes encoding other LiP isozymes shows five related patterns of intron location, whose incidence coincides with described LiP structural subfamilies. Codon bias indices calculated for all known P. chrysosporium genes, including trpC and genes encoding LiP, MnP, and exo-cellobiohydrolase I, demonstrate that LG2 has the most biased codon usage. We conclude that subdivisions of the LiP family may be based on intron location in the encoding genes, and that ranking of isozyme production levels can be estimated by the extent of bias in codon usage in the cognate gene.

Amino Acid Sequence↗
PubMed2025

Automated Machine Learning Tools to Build Regression Models for Schizosaccharomyces pombe Omics Data.

Machine learning is a powerful tool for analyzing biological data and making useful predictions. The surge of biological data from high-throughput omics technologies has raised the need for modeling approaches capable of tackling such amounts of data, which is pivotal to understanding the nature of complex molecular systems. Here, we show how to construct a simple model using automated machine learning (AutoML) to predict protein abundance in Schizosaccharomyces pombe, using data obtained from codon usage bias and quantitative proteomics.

Machine Learning↗
PubMed2006

Variation in synonymous codon use and DNA polymorphism within the Drosophila genome.

A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r(2) approximately 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called 'genetic draft' by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome.

Animals↗