Codon Usage Preferences

Codon usage bias plays an important role in the regulation of gene expression. A couple of measures are widely used to quantify the codon usage in genes. On the other hand, no quantitative endeavour has been made to compare the pattern of codon usage diversity within and between different genes of  Camellia sinensis and Brassica campestris . Nucleotide composition and its relationship with codon usage bias were analyzed. Additionally, the rare codons were identified by computing the recurrence of event of all codons in coding sequences of C. sinensis and B. campestris . The host cell, Escherichia coli used universally, failed to express smoothly many eukaryotic genes. For this, the authors prognosticated the codons showing the highest and the lowest expressivity of the coding sequences of  C. sinensis and B. campestris , in E. coli K12 strain to improve the expression level of the genes. Key words : Codon usage bias, gene expressivity, codon usage pattern, residual value, synonymous...

Background: SPANX (sperm protein coupled with the nucleus in the X chromosome) genes play a crucial role in human spermatogenesis. Codon usage bias (CUB) is a well-known phenomenon that exists in many genomes and mainly determined by mutation and selection. CUB is species specific and a unique characteristic of a genome. Analysis of compositional features and codon usage pattern of SPANX genes in human has contributed to explore the molecular biology of this gene. In our current study, we have retrieved the sequences of different variants of SPANX gene from NCBI using accession number and a perl script was used to analyze the nucleotide composition and the parameters for codon usage bias. Results: Our results showed that codon usage bias is low as measured by codon bias index (CBI) and most of the GC ending codons were positively correlated with GC bias as indicated by GC3. That mutation pressure and natural selection affect the codon usage pattern were revealed by correspondence analysis (COA) and neutrality plot. Moreover, the neutrality plot further suggested that the role of natural selection is higher than mutation pressure on SPANX genes. Conclusions: The codon usage bias in SPANX genes is not very high and the role of natural selection dominates over mutation pressure in the codon usage of human SPANX genes.

One of the central issues of evolutionary genomics is to find out the adaptive strategies of microorganisms to stabilize nucleic acid molecules under high temperature. Thermal adaptation hypothesis gives a link between G+C content and growth temperature if there is a considerable variation of guanine and cytosine content between species. However, there has been a long-standing debate regarding the correlations between genomic GC content and optimal growth temperature (Topt). We urged that adaptation to growth at high temperature requires a coordinated set of evolutionary changes affecting: (i) nucleic acid thermostability and (ii) stability of codon-anticodon interactions. Moreover, in Bacillaceae family we have demonstrated that a higher genomic GC level do not have any role in stabilizing mRNA secondary structure at high growth temperature. Comparative analysis between homologous sequences of thermophilic Thermus thermophilus and mesophilic Deinococcus radiodurans suggests that increased levels of GC contents in the coding sequence corresponding to strand structure of Thermus thermophilus genes have stabilizing effect on the mRNA secondary structure, whereas increased levels of GC contents in coding sequences corresponding to aperiodic structure have destabilizing effect on the mRNA secondary structure. In this perspective, a critical review of thermal adaptation hypothesis is further advocated.

Translation elongation efficiency is largely thought of as the sum of decoding efficiencies for individual codons. Here, we find that adjacent codon pairs modulate translation efficiency. Deploying an approach in Saccharomyces cerevisiae that scored the expression of over 35,000 GFP variants in which three adjacent codons were randomized, we identified 17 pairs of adjacent codons associated with reduced expression. For many pairs, codon order is obligatory for inhibition, implying a more complex interaction than a simple additive effect. Inhibition mediated by adjacent codons occurs during translation itself as GFP expression is restored by increased tRNA levels or by non-native tRNAs with exact-matching anticodons. Inhibition operates in endogenous genes, based on analysis of ribosome profiling data. Our findings suggest translation efficiency is modulated by an interplay between tRNAs at adjacent sites in the ribosome, and that this concerted effect needs to be considered in predicting the functional consequences of codon choice.

Cête d׳Ivoire continues to have the highest HIV-1 prevalence rate in West Africa, although the infection number is in constant decline. The external envelope protein of the viruses is a likely site of selection, and responsible for receptor binding and entry into host cells, and therefore constitutes an ideal region with which to investigate the evolutionary processes acting on HIV-1. In this study, we analyse 189 envelope glycoprotein V3 loop region sequences of viruse isolates from 1995 to 2009, from HIV-1 untreated patients living in Cête d׳Ivoire, to decipher the temporal relationship between disease diversity, divergence and selection. Our analyses show that the nonsynonymous and synonymous ratio (dN/dS) was lower than 1 for viral populations analysed within 15 years, which showed the sequences did not undergo adequate immune pressure. The phylogenetic tree of the sequences analysed demonstrated distinctly long internal branches and short external branches, suggesting that only...

Analysis of codon usage pattern is important to understand the genetic and evolutionary characteristics of genomes. We have used bioinformatic approaches to analyze the codon usage bias (CUB) of the genes located in human Y chromosome. Codon bias index (CBI) indicated that the overall extent of codon usage bias was low. The relative synonymous codon usage (RSCU) analysis suggested that approximately half of the codons out of 59 synonymous codons were most frequently used, and possessed a T or G at the third codon position. The codon usage pattern was different in different genes as revealed from correspondence analysis (COA). A significant correlation between effective number of codons (ENC) and various GC contents suggests that both mutation pressure and natural selection affect the codon usage pattern of genes located in human Y chromosome. In addition, Y-linked genes have significant difference in GC contents at the second and third codon positions, expression level, and codon us...

Background: Mitochondrial ND gene, which encodes NADH dehydrogenase, is the first enzyme of the mitochondrial electron transport chain. Leigh syndrome, a neurodegenerative disease caused by mutation in the ND2 gene (T4681C), is associated with bilateral symmetric lesions in basal ganglia and subcortical brain regions. Therefore, it is of interest to analyze mitochondrial DNA to glean information for evolutionary relationship. This study highlights on the analysis of compositional dynamics and selection pressure in shaping the codon usage patterns in the coding sequence of MT-ND2 gene across pisces, aves and mammals by using bioinformatics tools like effective number of codons (ENC), codon adaptation index (CAI), relative synonymous codon usage (RSCU) etc. Results: We observed a low codon usage bias as reflected by high ENC values in MT-ND2 gene among pisces, aves and mammals. The most frequently used codons were ending with A/C at the 3 rd position of codon and the gene was AT rich in all the three classes. The codons TCA, CTA, CGA and TGA were over represented in all three classes. The F1 correspondence showed significant positive correlation with G, T3 and CAI while the F2 axis showed significant negative correlation with A and T but significant positive correlation with G, C, G3, C3, ENC, GC, GC1, GC2 and GC3. Conclusions: The codon usage bias in MT-ND2 gene is not associated with expression level. Mutation pressure and natural selection affect the codon usage pattern in MT-ND 2 gene.

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage (RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein al...

Analysis of synonymous codon usage pattern in the genome of a thermophilic cyanobacterium, Thermosynechococcus elongatus BP-1 using multivariate statistical analysis revealed a single major explanatory axis accounting for codon usage variation in the organism. This axis is correlated with the GC content at third base of synonymous codons (GC3s) in correspondence analysis taking T. elongatus genes. A negative correlation was observed between effective number of codons i.e. Nc and GC3s. Results suggested a mutational bias as the major factor in shaping codon usage in this cyanobacterium. In comparison to the lowly expressed genes, highly expressed genes of this organism possess significantly higher proportion of pyrimidine-ending codons suggesting that besides, mutational bias, translational selection also influenced codon usage variation in T. elongatus. Correspondence analysis of relative synonymous codon usage (RSCU) with A, T, G, C at third positions (A3s, T3s, G3s, C3s, respectively) also supported this fact and expression levels of genes and gene length also influenced codon usage. A role of translational accuracy was identified in dictating the codon usage variation of this genome. Results indicated that although mutational bias is the major factor in shaping codon usage in T. elongatus, factors like translational selection, translational accuracy and gene expression level also influenced codon usage variation.

tRNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs) derived from tRNAs. tRFs are highly abundant in many cell types including stem cells and cancer cells, and are found in all domains of life. Beyond translation control, tRFs have several functions ranging from transposon silencing to cell proliferation control. However, the analysis of tRFs presents specific challenges and their biogenesis is not well understood. They are very heterogeneous and highly modified by numerous post-transcriptional modifications. Here we describe a bioinformatic pipeline to study tRFs populations and shed light onto tRNA fragments biogenesis. Indeed, we used small RNAs Illumina sequencing datasets extracted from wild type and mutant Drosophila ovaries affecting two different highly conserved steps of tRNA biogenesis: 5'pre-tRNA processing (RNase-P subunit Rpp30) and tRNA 2'-O-methylation (CG7009 and CG5220). Using our pipeline, we show how defects in tRNA biogenesis affect nuclea...

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage (RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein al...

Analysis of synonymous codon usage pattern in the genome of a thermophilic cyanobacterium, Thermosynechococcus elongatus BP-1 using multivariate statistical analysis revealed a single major explanatory axis accounting for codon usage variation in the organism. This axis is correlated with the GC content at third base of synonymous codons (GC3s) in correspondence analysis taking T. elongatus genes. A negative correlation was observed between effective number of codons i.e. Nc and GC3s. Results suggested a mutational bias as the major factor in shaping codon usage in this cyanobacterium. In comparison to the lowly expressed genes, highly expressed genes of this organism possess significantly higher proportion of pyrimidine-ending codons suggesting that besides, mutational bias, translational selection also influenced codon usage variation in T. elongatus. Correspondence analysis of relative synonymous codon usage (RSCU) with A, T, G, C at third positions (A3s, T3s, G3s, C3s, respectively) also supported this fact and expression levels of genes and gene length also influenced codon usage. A role of translational accuracy was identified in dictating the codon usage variation of this genome. Results indicated that although mutational bias is the major factor in shaping codon usage in T. elongatus, factors like translational selection, translational accuracy and gene expression level also influenced codon usage variation.

The phenotypes of biological systems are to some extent robust to genotypic changes. Such robustness exists on multiple levels of biological organization. We analyzed this robustness for two categories of amino acids in proteins. Specifically, we studied the codons of amino acids that bind or do not bind small molecular ligands. We asked to what extent codon changes caused by mutation or mistranslation may affect physicochemical amino acid properties or protein folding. We found that the codons of ligand-binding amino acids are on average more robust than those of non-binding amino acids. Because mistranslation is usually more frequent than mutation, we speculate that selection for error mitigation at the translational level stands behind this phenomenon. Our observations suggest that natural selection can affect the robustness of very small units of biological organization.

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage (RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein also influence the codon usage variation of genes to some extent. A comparison of the relative synonymous codon usage between 10% each of highly and lowly expressed genes determines 23 optimal codons, which are statistically over represented in the former group of genes and may provide useful information for salt-stressed gene prediction and gene-transformation. Furthermore, genes for regulatory functions; mobile and extrachromosomal element functions; and cell envelope are observed to be highly expressed. The study could provide insight into the gene expression response of halophilic bacteria and facilitate establishment of effective strategies to develop salt-tolerant crops of agronomic value.

OPTIMIZER is an on-line application that optimizes the codon usage of a gene to increase its expression level. Three methods of optimization are available: the 'one amino acid-one codon' method, a guided random method based on a Monte Carlo algorithm, and a new method designed to maximize the optimization with the fewest changes in the query sequence. One of the main features of OPTIMIZER is that it makes it possible to optimize a DNA sequence using pre-computed codon usage tables from a predicted group of highly expressed genes from more than 150 prokaryotic species under strong translational selection. These groups of highly expressed genes have been predicted using a new iterative algorithm. In addition, users can use, as a reference set, a precomputed table containing the mean codon usage of ribosomal protein genes and, as a novelty, the tRNA gene-copy numbers. OPTIMIZER is accessible free of charge at http://genomes.urv.es/ OPTIMIZER.

Cells control the efficiency of translation with various protein regulatory factors. Using computational approaches, both Tuller et al. and Cannarozzi et al. now find that translational efficiency is also hardwired into the transcript sequence. Tuller et al. show that messages often start with codons that correspond to rare transfer RNAs (tRNAs). This forms an early elongation "ramp" that fosters slow translation and may maximize the efficiency of protein production. Cannarozzi et al. find that once a codon for a particular amino acid is used, the subsequent codons for that amino acid are likely to be the same, despite the availability of multiple codons for each amino acid. This correlation is highly conserved across organisms and is shown to increase translation speed, suggesting that tRNAs are recycled and channeled by the ribosome.

Background: Mitochondrial ND gene, which encodes NADH dehydrogenase, is the first enzyme of the mitochondrial electron transport chain. Leigh syndrome, a neurodegenerative disease caused by mutation in the ND2 gene (T4681C), is associated with bilateral symmetric lesions in basal ganglia and subcortical brain regions. Therefore, it is of interest to analyze mitochondrial DNA to glean information for evolutionary relationship. This study highlights on the analysis of compositional dynamics and selection pressure in shaping the codon usage patterns in the coding sequence of MT-ND2 gene across pisces, aves and mammals by using bioinformatics tools like effective number of codons (ENC), codon adaptation index (CAI), relative synonymous codon usage (RSCU) etc. Results: We observed a low codon usage bias as reflected by high ENC values in MT-ND2 gene among pisces, aves and mammals. The most frequently used codons were ending with A/C at the 3 rd position of codon and the gene was AT rich in all the three classes. The codons TCA, CTA, CGA and TGA were over represented in all three classes. The F1 correspondence showed significant positive correlation with G, T3 and CAI while the F2 axis showed significant negative correlation with A and T but significant positive correlation with G, C, G3, C3, ENC, GC, GC1, GC2 and GC3. Conclusions: The codon usage bias in MT-ND2 gene is not associated with expression level. Mutation pressure and natural selection affect the codon usage pattern in MT-ND 2 gene.

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This study was attempted to focus on the pattern of codon usage bias (CUB) of chloroplast genes in two species of Pisum viz. P. fulvum and P. sativum and to identify the factors which influence CUB. Bioinformatic tools were used to understand codon usage pattern in the protein-coding sequences of Pisum chloroplast genomes. It was found that GC content was lower than AT content in the genes. Low synonymous codon usage order (SCUO) values of genes indicated low CUB in chloroplast genes of Pisum species. Heatmaps showed positive correlations of GC3 with all the GC and AT ending codons. Neutrality plot analysis revealed that natural selection might have played a prominent role over mutation pressure in sculpturing the CUB of chloroplast genes in these two taxa. Positive correlation between SCUO and mRNA free energy (mFE) suggested that higher energy release by entire mRNA was related to high degree of CUB. Further, highly significant (p < .01) negative correlation was found between parameters in pair i.e. mFE-GC, mFE-GC1, mFE-GC2 and mFE for entire mRNA-GC3. This pointed out that higher GC content might have influenced lesser energy release by mRNA molecules of chloroplast genes.

Genital Human Papillomavirus (HPV) infection is a self-limiting and often asymptomatic disease. Genital HPV infection is divided into high-risk HPV (HPV 16 and 18) and low-risk HPV (HPV 6 and 11). Low-risk or non-oncogenic HPV produces a clinical picture of anogenital warts, which may be condylomatous, papules, or keratotic. The subclinical form of genital HPV infection can present with an &quot;aceto-white&quot; lesion found on the cervix that will appear when examined using an acetic acid solution evaluated by colposcopy. Based on the association with cervical cancer and precursor lesions, HPV can also be classified as high-risk (HR-HPV) and low-risk (LR-HPV) oncogenic types. LR-HPV types, such as HPV 6 and 11, can cause generalized genital warts or benign hyperproliferative lesions with a very limited predisposition to malignant progression, while infection with HR-HPV types, HPV 16 and 18, is associated with the development of pre-malignant and cervical lesions. Discussion: Huma...

The purpose of this study is to identify and analyse the putative promoter motifs in the bovine herpes virus which causes several diseases in cattle worldwide including bovine mastitis with large economic impact on dairy industry. Bovine mastitis caused due to virus is often neglected as bacterial infections are held mainly responsible for the disease. Therefore, in this in silico investigation with all the existing experimental data a total of 147 promoter were identified along with their sequences from three genome viz bovine herpes virus 1 (BHV), bovine herpes virus 4 and bovine herpes virus 5, out of which 39 promoters were from bovine herpes virus 4 (BHV 4), 95 from BHV1 and 13 from BHV5 and it was observed that BHV1 and BHV5 have a close evolutionary history. However, they belong to the same subfamily and size of the genome and GC% of BHV1 and BHV5 was almost equal and very high compare to that of BHV4. This analysis may help in designing the live attenuated vaccine against BHV causing bovine mastitis that reduces the incidence of bovine mastitis. Identification of promoters may also help in designing of expression vectors which help in better understanding of the regulation of gene expression. In the era of large genomics and proteomics prediction of promoters in the whole genome is crucial for the advancement of drug discovery and gene therapy.