Strand-specific Mutational Bias Research Articles

The nucleotide usages significantly impact synonymous codon usage in Mycoplasma hyorhinis.

Five annotated genomes of Mycoplasma hyorhinis were analyzed for clarifying evolutionary dynamics driving the overall codon usage pattern. Information entropy used for estimating nucleotide usage pattern at the gene level indicates that multiple evolutionary dynamics participate in forcing nucleotide usage bias at every codon position. Moreover, nucleotide usage bias directly contributes to synonymous codon usage biases with two different extremes. The overrepresented codons tended to have A/T in the third codon position, and the underrepresented codons strongly used G/C in the third position. Furthermore, correspondence analysis and neutrality plot reflect an obvious interplay between mutation pressure and natural selection mediating codon usage in M. hyorhinis genome. Due to significant bias in usages between A/T and G/C at the gene level, different selective forces have been proposed to contribute to codon usage preference in M. hyorhinis genome, including nucleotide composition constraint derived from mutation pressure, translational selection involved in natural selection, and strand-specific mutational bias represented by different nucleotide skew index. The systemic analyses of codon usage for M. hyorhinis can enable us to better understand the mechanisms of evolution in this species.

Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.

The effect of multiple evolutionary selections on synonymous codon usage of genes in the Mycoplasma bovis genome.

Mycoplasma bovis is a major pathogen causing arthritis, respiratory disease and mastitis in cattle. A better understanding of its genetic features and evolution might represent evidences of surviving host environments. In this study, multiple factors influencing synonymous codon usage patterns in M. bovis (three strains’ genomes) were analyzed. The overall nucleotide content of genes in the M. bovis genome is AT-rich. Although the G and C contents at the third codon position of genes in the leading strand differ from those in the lagging strand (p<0.05), the 59 synonymous codon usage patterns of genes in the leading strand are highly similar to those in the lagging strand. The over-represented codons and the under-represented codons were identified. A comparison of the synonymous codon usage pattern of M. bovis and cattle (susceptible host) indicated the independent formation of synonymous codon usage of M. bovis. Principal component analysis revealed that (i) strand-specific mutational bias fails to affect the synonymous codon usage pattern in the leading and lagging strands, (ii) mutation pressure from nucleotide content plays a role in shaping the overall codon usage, and (iii) the major trend of synonymous codon usage has a significant correlation with the gene expression level that is estimated by the codon adaptation index. The plot of the effective number of codons against the G+C content at the third codon position also reveals that mutation pressure undoubtedly contributes to the synonymous codon usage pattern of M. bovis. Additionally, the formation of the overall codon usage is determined by certain evolutionary selections for gene function classification (30S protein, 50S protein, transposase, membrane protein, and lipoprotein) and translation elongation region of genes in M. bovis. The information could be helpful in further investigations of evolutionary mechanisms of the Mycoplasma family and heterologous expression of its functionally important proteins.

Analysis of the genome and proteome composition of Bdellovibrio bacteriovorus: Indication for recent prey-derived horizontal gene transfer

The genome/proteome composition of Bdellovibrio bacteriovorus, the predatory microorganism that preys on other Gram-negative bacteria, has been analyzed. The study elucidates that translational selection plays a major role in genome compositional variation with higher intensity compared to other deltaproteobacteria. Other sources of variations having relatively minor contributions are local GC-bias, horizontal gene transfer and strand-specific mutational bias. The study identifies a group of AT-rich genes with distinct codon composition that is presumably acquired by Bdellovibrio recently from Gram-negative prey-bacteria other than deltaproteobacteria. The proteome composition of this species is influenced by various physico-chemical factors, viz, alcoholicity, residue-charge, aromaticity and hydropathy. Cell-wall-surface-anchor-family (CSAPs) and transporter proteins with distinct amino acid composition and specific secondary-structure also contribute notably to proteome compositional variation. CSAPs, which are low molecular-weight, outer-membrane proteins with highly disordered secondary-structure, have preference toward polar-uncharged residues and cysteine that presumably help in prey-predator interaction by providing particular bonds of attachment.

The enigmatic mitochondrial genome of Rhabdopleura compacta(Pterobranchia) reveals insights into selection of an efficient tRNA system and supports monophyly of Ambulacraria

BackgroundThe Hemichordata comprises solitary-living Enteropneusta and colonial-living Pterobranchia, sharing morphological features with both Chordata and Echinodermata. Despite their key role for understanding deuterostome evolution, hemichordate phylogeny is controversial and only few molecular data are available for phylogenetic analysis. Furthermore, mitochondrial sequences are completely lacking for pterobranchs. Therefore, we determined and analyzed the complete mitochondrial genome of the pterobranch Rhabdopleura compacta to elucidate deuterostome evolution. Thereby, we also gained important insights in mitochondrial tRNA evolution.ResultsThe mitochondrial DNA of Rhabdopleura compacta corresponds in size and gene content to typical mitochondrial genomes of metazoans, but shows the strongest known strand-specific mutational bias in the nucleotide composition among deuterostomes with a very GT-rich main-coding strand. The order of the protein-coding genes in R. compacta is similar to that of the deuterostome ground pattern. However, the protein-coding genes have been highly affected by a strand-specific mutational pressure showing unusual codon frequency and amino acid composition. This composition caused extremely long branches in phylogenetic analyses. The unusual codon frequency points to a selection pressure on the tRNA translation system to codon-anticodon sequences of highest versatility instead of showing adaptations in anticodon sequences to the most frequent codons. Furthermore, an assignment of the codon AGG to Lysine has been detected in the mitochondrial genome of R. compacta, which is otherwise observed only in the mitogenomes of some arthropods. The genomes of these arthropods do not have such a strong strand-specific bias as found in R. compacta but possess an identical mutation in the anticodon sequence of the tRNALys.ConclusionA strong reversed asymmetrical mutational constraint in the mitochondrial genome of Rhabdopleura compacta may have arisen by an inversion of the replication direction and adaptation to this bias in the protein sequences leading to an enigmatic mitochondrial genome. Although, phylogenetic analyses of protein coding sequences are hampered, features of the tRNA system of R. compacta support the monophyly of Ambulacraria. The identical reassignment of AGG to Lysine in two distinct groups may have occurred by convergent evolution in the anticodon sequence of the tRNALys.

Strand‐specific mutational bias influences codon usage of weakly expressed genes in Escherichia coli

According to the selection-mutation-drift theory of molecular evolution, mutation predominates in determining codon usage bias (CUB) in weakly expressed genes (WEG) whereas selection predominates in determining CUB in highly expressed genes (HEG). Strand-specific mutational bias causes compositional asymmetry of the nucleotides between leading and lagging strands (LaS) in bacterial chromosomes. Keeping in view the aforementioned points, CUB between the strands were compared in Escherichia coli chromosome. In comparison with HEG, codon usage of WEG was observed to be more biased toward strands: G ending codons were significantly more in leading strands than in LaS and the reverse was true for the C ending codons. In case of WEG, the GC(3) skews were found to be significantly different between the strands. This suggests that strand-specific mutational bias influences codon usage of WEG to a greater extent than that of HEG. The differential effect of strand-specific mutational bias in E. coli might be attributed to stronger purifying selection in the HEG than the WEG. The observation here in E. coli supports the SMD theory of molecular evolution.

Codon Usages of Genes on Chromosome, and Surprisingly, Genes in Plasmid are Primarily Affected by Strand-specific Mutational Biases in Lawsonia intracellularis

In this study, the factors driving genome-wide patterns of codon usages in Lawsonia intracellularis genome are determined. For genes on the chromosome of the bacterium, it is found that the most important source of variation results from strand-specific mutational biases. A lesser trend of variation is attributable to genes that are presumed as horizontally transferred. These putative alien genes are unusually GC richer than the other genes, whereas horizontally transferred genes have been observed to be AT rich in bacteria with medium and relatively low G + C contents. Hydropathy of encoded protein and expression level are also found to influence codon usage. Therefore, codon usage in L. intracellularis chromosome is the result of a complex balance among the different mutational and selectional factors. When analyzing genes in the largest plasmid, for the first time it is found that the strand-specific mutational biases are responsible for the primary variation of codon usages in plasmid. Genes, particularly highly expressed genes of this plasmid, are mainly located on the leading strands and this supposed to be the effects exerted by replicational–transcriptional selection. These facts suggest that this plasmid adopts the similar mechanism of replication as the chromosome in L. intracellularis. Common characters among the 10 bacteria in whose genomes the strand-specific mutational biases are the primary source of variation of codon usage are also investigated. For example, it is found that genes dnaT and fis that are involved in DNA replication initiation and re-initiation pathways are absent in all of the 10 bacteria.

The Mitochondrial Genome of a Deep-Sea Bamboo Coral (Cnidaria, Anthozoa, Octocorallia, Isididae): Genome Structure and Putative Origins of Replication Are Not Conserved Among Octocorals

Octocoral mitochondrial (mt) DNA is subject to an exceptionally low rate of substitution, and it has been suggested that mt genome content and structure are conserved across the subclass, an observation that has been supported for most octocorallian families by phylogenetic analyses using PCR products spanning gene boundaries. However, failure to recover amplification products spanning the nad4L-msh1 gene junction in species from the family Isididae (bamboo corals) prompted us to sequence the complete mt genome of a deep-sea bamboo coral (undescribed species). Compared to the "typical" octocoral mt genome, which has 12 genes transcribed on one strand and 5 genes on the opposite (cox2, atp8, atp6, cox3, trnM), in the bamboo coral genome a contiguous string of 5 genes (msh1, rnl, nad2, nad5, nad4) has undergone an inversion, likely in a single event. Analyses of strand-specific compositional asymmetry suggest that (i) the light-strand origin of replication was also inverted and is adjacent to nad4, and (ii) the orientation of the heavy-strand origin of replication (OriH) has reversed relative to that of previously known octocoral mt genomes. Comparative analyses suggest that intramitochondrial recombination and errors in replication at OriH may be responsible for changes in gene order in octocorals and hexacorals, respectively. Using primers flanking the regions at either end of the inverted set of five genes, we examined closely related taxa and determined that the novel gene order is restricted to the deep-sea subfamily Keratoisidinae; however, we found no evidence for strand-specific mutational biases that may influence phylogenetic analyses that include this subfamily of bamboo corals.

Insect mitochondrial genomics 2: the complete mitochondrial genome sequence of a giant stonefly,Pteronarcys princeps, asymmetric directional mutation bias, and conserved plecopteran A+T-region elements

Mitochondrial (mt) genome sequences of insects are receiving renewed attention in molecular phylogentic studies, studies of mt-genome rearrangement, and other unusual molecular phenomena, such as translational frameshifting. At present, the basal neopteran lineages are poorly represented by mt-genome sequences. Complete mt-genome sequences are available in the databases for only the Orthoptera and Blatteria; 9 orders are unrepresented. Here, we present the complete mt-genome sequence of a giant stonefly, Pteronarcys princeps (Plecoptera; Pteronarcyidae). The 16,004 bp genome is typical in its genome content, gene organisation, and nucleotide composition. The genome shows evidence of strand-specific mutational biases, correlated with the time between the initiation of leading and the initiation of lagging strand replication. Comparisons with other insects reveal that this trend is seen in other insect groups, but is not universally consistent among sampled mt-genomes. The A+T region is compared with that of 2 stoneflies in the family Peltoperlidae. Conserved stem-loop structures and sequence blocks are noted between these distantly related families.

Evolutionary Constraints on Codon and Amino Acid Usage in Two Strains of Human Pathogenic Actinobacteria Tropheryma whipplei

The factors governing codon and amino acid usages in the predicted protein-coding sequences of Tropheryma whipplei TW08/27 and Twist genomes have been analyzed. Multivariate analysis identifies the replicational-transcriptional selection coupled with DNA strand-specific asymmetric mutational bias as a major driving force behind the significant interstrand variations in synonymous codon usage patterns in T. whipplei genes, while a residual intrastrand synonymous codon bias is imparted by a selection force operating at the level of translation. The strand-specific mutational pressure has little influence on the amino acid usage, for which the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact. In spite of the intracellular lifestyle, the amino acid usage in highly expressed gene products of T. whipplei follows the cost-minimization hypothesis. The products of the highly expressed genes of these relatively A + T-rich actinobacteria prefer to use the residues encoded by GC-rich codons, probably due to greater conservation of a GC-rich ancestral state in the highly expressed genes, as suggested by the lower values of the rate of nonsynonymous divergences between orthologous sequences of highly expressed genes from the two strains of T. whipplei. Both the genomes under study are characterized by the presence of two distinct groups of membrane-associated genes, products of which exhibit significant differences in primary and potential secondary structures as well as in the propensity of protein disorder.

Synonymous codon usage in environmental chlamydia UWE25 reflects an evolutional divergence from pathogenic chlamydiae

Publication of the complete genome sequence for the Acanthamoeba sp. endosymbiont UWE25 has illuminated the evolution history of chlamydiae. In this study, the codon usage bias in UWE25 and five other species of pathogenic chlamydiae was calculated. It was found that genomic composition constraints are the major source of codon usage variation in UWE25. This result is different from the former observation in pathogenic chlamydiae, whose genomic base composition is more unbiased. Four other factors, such as strand-specific mutational bias, natural selection acting at the level of translation, hydropathy level of each protein and the conservation level of amino acids also have influence in shaping the codon usage in these six species to some extent. Further analysis suggests that the high stability of the UWE25 genome partially account for the difference in codon usage pattern between environmental and pathogenic chlamydiae. Moreover, our results imply that the replicational selection pressure in pathogenic chlamydiae is stronger than that in UWE25. Analyzing the codon usage pattern in the environmental chlamydia and comparing it with that of the pathogenic chlamydiae may provide clues how the chlamydiae have evolved from their common ancestor.

Evolutionary Forces in Shaping the Codon and Amino Acid Usages in Blochmannia floridanus

Endosymbiotic relationship has great effect on ecological system. Codon and amino acid usages bias of endosymbiotic bacteria Blochmannia floridanus (whose host is an ant Camponotus floridanus) was investigated using experimentally known genes of this organism. Correspondence Analysis on RSCU values show that there exists only one single explanatory major axis that is linked to the strand specific mutational biases. Majority of the genes have a tendency to concentrate on the leading strand, which may be related to the adaptive property related to the replication mechanisms. Amino acid usages were markedly different between the highly and lowly expressed genes in this organism and in particular, GC rich amino acids were found to occur significantly higher in highly expressed genes than the lowly expressed genes. Comparative analyses of the orthologous genes of Escherichia coli and Blochmannia floridanus show that highly expressed genes are significantly more conserved than lowly expressed genes. Based on our results we concluded that strand specific mutational bias is strongly operational in selecting the codon usage in this organism. Replicational-transcriptional selection can be invoked from the presence of majority of highly expressed genes in the leading strand. Conservation of GC rich amino acids in the highly expressed genes to its ancestor is the major source of variation in amino acid usages in the organism. Hydrophobicity of the genes is the second major source in differentiating the genes according to their amino acid usages in this organism.

Synonymous Codon Usage in Bacteria

In most bacteria, synonymous codons are not used with equal frequencies. Different factors have been proposed to contribute to codon usage preference, including translational selection, GC composition, strand-specific mutational bias, amino acid conservation, protein hydropathy, transcriptional selection and even RNA stability. The review discusses these factors and their contribution to bias in synonymous codon usage in bacterial genomes.

Codon usage in Chlamydia trachomatis is the result of strand-specific mutational biases and a complex pattern of selective forces.

The patterns of synonymous codon choices of the completely sequenced genome of the bacterium Chlamydia trachomatis were analysed. We found that the most important source of variation among the genes results from whether the sequence is located on the leading or lagging strand of replication, resulting in an over representation of G or C, respectively. This can be explained by different mutational biases associated to the different enzymes that replicate each strand. Next we found that most highly expressed sequences are located on the leading strand of replication. From this result, replicational-transcriptional selection can be invoked. Then, when the genes located on the leading strand are studied separately, the correspondence analysis detects a principal trend which discriminates between lowly and highly expressed sequences, the latter displaying a different codon usage pattern than the former, suggesting selection for translation, which is reinforced by the fact that Ks values between orthologous sequences from C. trachomatis and Chlamydia pneumoniae are much smaller in highly expressed genes. Finally, synonymous codon choices appear to be influenced by the hydropathy of each encoded protein and by the degree of amino acid conservation. Therefore, synonymous codon usage in C.trachomatis seems to be the result of a very complex balance among different factors, which rises the problem of whether the forces driving codon usage patterns among microorganisms are rather more complex than generally accepted.

Proteome composition and codon usage in spirochaetes: species-specific and DNA strand-specific mutational biases.

The genomes of the spirochaetes Borrelia burgdorferi and Treponema pallidum show strong strand-specific skews in nucleotide composition, with the leading strand in replication being richer in G and T than the lagging strand in both species. This mutation bias results in codon usage and amino acid composition patterns that are significantly different between genes encoded on the two strands, in both species. There are also substantial differences between the species, with T.pallidum having a much higher G+C content than B. burgdorferi. These changes in amino acid and codon compositions represent neutral sequence change that has been caused by strong strand- and species-specific mutation pressures. Genes that have been relocated between the leading and lagging strands since B. burgdorferi and T.pallidum diverged from a common ancestor now show codon and amino acid compositions typical of their current locations. There is no evidence that translational selection operates on codon usage in highly expressed genes in these species, and the primary influence on codon usage is whether a gene is transcribed in the same direction as replication, or opposite to it. The dnaA gene in both species has codon usage patterns distinctive of a lagging strand gene, indicating that the origin of replication lies downstream of this gene, possibly within dnaN. Our findings strongly suggest that gene-finding algorithms that ignore variability within the genome may be flawed.