Codon usage pattern and evolutionary forces of mitochondrial ND genes among orders of class Amphibia.

In this study, we used a bioinformatics approach to analyze the nucleotide composition and pattern of synonymous codon usage in mitochondrial ND genes in three amphibian groups, that is, orders Anura, Caudata, and Gymnophiona to identify the commonality and the differences of codon usage as no research work was reported yet. The high value of the effective number of codons revealed that the codon usage bias (CUB) was low in mitochondrial ND genes among the orders. Nucleotide composition analysis suggested that for each gene, the compositional features differed among Anura, Caudata, and Gymnophiona and the GC content was lower than AT content. Furthermore, a highly significant difference (p < .05) for GC content was found in each gene among the orders. The heat map showed contrasting patterns of codon usage among different ND genes. The regression of GC12 on GC3 suggested a narrow range of GC3 distribution and some points were located in the diagonal, indicating both mutation pressure and natural selection might influence the CUB. Moreover, the slope of the regression line was less than 0.5 in all ND genes among orders, indicating natural selection might have played the dominant role whereas mutation pressure had played a minor role in shaping CUB of ND genes across orders.

Similarities and dissimilarities of codon usage in mitochondrial ATP genes among fishes, aves, and mammals.

In this study, we used bioinformatic approach to analyze the compositional features and codon usage bias (CUB) of ATP6 and ATP8 genes among three groups, namely, fishes, aves, and mammals which thrive in three different habitats as no work was reported yet. The coding sequences of these genes were retrieved from the National Center for Biotechnology Information to explore the similarities and dissimilarities of codon usage of each gene among these groups. Low values of synonymous codon usage order in fishes, aves, and mammals for ATP6 and ATP8 genes suggested that the CUB of ATP6 and ATP8 genes was low. In ATP6 gene, overall GC contents in fishes, aves and mammals were (mean ± SD) 44.09 ± 3.10, 46.65 ± 1.90, and 39.41 ± 2.89%, respectively, whereas in ATP8 gene, the overall GC contents were 42.76 ± 4.38, 44.16 ± 2.43, and 34.19 ± 3.82% in fishes, aves, and mammals, that is, both genes were found to be AT rich. In ATP6 gene, the codon AGC was overrepresented in fishes but under-represented in aves and mammals, whereas in ATP8 gene, the codon GCC was overrepresented in fishes but underrepresented in aves and mammals. The pattern of codon usage was different in these genes and varied among groups as evident from correspondence analysis. The slope of the regression line in neutrality plot was lower than 0.5, which revealed that the role of natural selection was higher than mutation pressure in shaping the CUB in ATP6 and ATP8 genes.

Codon usage trend in genes associated with obesity.

Obesity is not only a social menace but also an economic burden as it reduces productivity and increases health care cost. We used bioinformatic tools to analyze the CUB of obesity associated genes and compared with housekeeping genes (control) to explore the similarities and differences between two data sets as no work was reported yet. The mean effective number of codons (ENC) in genes associated with obesity and housekeeping gene was 50.45 and 52.03 respectively, indicating low CUB. The relative synonymous codon usage (RSCU) suggested that codons namely CTG and GTG were over-represented in both obesity and housekeeping genes while under-represented codons were TCG, TTA, CTA, CCG, CAA, CGT, ATA, ACG, GTA and GCG in obesity genes and TCG, TTA, CCG, ATA, ACG, GTA, and GCG in housekeeping genes. t test analysis suggested that 11 codons namely TTA (Leu), TTG (Leu), CCG (Pro), CAC (His), CAA (Gln), CAG (Gln), CGT (Arg), AGA (Arg), ATA (Ile), ATT (Ile) and GCG (Ala) were significantly differed (p < 0.05 or p < 0.01) between obesity and housekeeping genes. Highly significant correlation was observed between GC12 and GC3 in obesity and housekeeping genes i.e. r = 0.580** and r = 0.498** (p < 0.01) respectively indicating the effect of directional mutation pressure present in all codon positions.

Genome-wide comparison of codon usage dynamics in mitochondrial genes across different species of amphibian genus Bombina.

The biological phenomenon where some synonymous codons are repeatedly preferred to others in gene transcripts is called codon usage bias (CUB). The analysis of CUB is not only helpful in evolutionary biology but also in improving the expression level of exogenous genes in the host cell by codon optimization. The overall nucleotide composition analysis demonstrated an unequal distribution of four nucleobases and T% was the highest in all seven species. The genes were AT-rich, evident from overall low GC content. In addition, third codon position analysis indicated that in four Bombina species namely, Bombina fortinuptialis, Bombina lichuanensis, Bombina maxima, Bombina microdeladigitora, nucleobase A3/T3 was the preferred one, whereas A3/C3 was favored in Bombina bombina, Bombina orientalis, and Bombina variegata. Influence of mutation pressure on codon distribution and codon bias was evident from correlation analysis. Correspondence analysis demonstrated that compositional bias driven by mutation pressure along with natural selection acted on CUB of mitochondrial genes. Neutrality plot revealed that natural selection played a major role whereas mutation pressure had a minor but significant role. Our phylogenetic analyses showed that closely linked species belonging to the same genus were noticeably separated in different clades.

Understanding the codon usage patterns of mitochondrial CO genes among Amphibians.

A universal phenomenon of using synonymous codons unequally in coding sequences known as codon usage bias (CUB) is observed in all forms of life. Mutation and natural selection drive CUB in many species but the relative role of evolutionary forces varies across species, genes and genomes. We studied the CUB in mitochondrial (mt) CO genes from three orders of Amphibia using bioinformatics approach as no work was reported yet. We observed that CUB of mt CO genes of Amphibians was weak across different orders. Order Caudata had higher CUB followed by Gymnophiona and Anura for all genes and CUB also varied across genes. Nucleotide composition analysis showed that CO genes were AT-rich. The AT content in Caudata was higher than that in Gymnophiona while Anura showed the least content. Multiple investigations namely nucleotide composition, correspondence analysis, parity plot analysis showed that the interplay of mutation pressure and natural selection caused CUB in these genes. Neutrality plot suggested the involvement of natural selection was more than the mutation pressure. The contribution of natural selection was higher in Anura than Gymnophiona and the lowest in Caudata. The codons CGA, TGA, AAA were found to be highly favoured by nature across all genes and orders.

Silencing lung cancer genes using miRNAs identified by 7mer-seed matching.

Lung cancer (LC) is the main cause of cancer-associated deaths in both men and women globally with a very high mortality rate. The microRNAs (miRNAs) are a class of noncoding RNAs consisting of 18-25 nucleotides. They inhibit translation of protein through binding to complementary target mRNAs. The non-coding miRNAs are recognized as potent biomarkers for detection, development and treatment of malignancy. In this study, we screened a set of 12 genes over expressed in small cell lung cancer, non small cell lung cancer and the genes involved in both categories and their binding sites for human miRNAs as no work was reported yet. Screening of human miRNAs revealed that a few genes showed numerous miRNA binding sites. Free energy values of mRNA sequences revealed that they might acquire compact folded structure causing complexity for miRNAs to interact. GC content in the target site was relatively higher than that of their flanks. It was observed through analysis of cosine similarity metric and compAI parameters that the genes related to lung cancer were encoded with non optimal codons and thus might be translationally less efficient for producing polypeptides. Gene ontology analysis was carried out to understand the diverse functions of these 12 genes.

Analysis of compositional properties and codon usage bias of mitochondrial CYB gene in anura, urodela and gymnophiona.

We delineated the pattern of synonymous codon usage bias (CUB) and its determinants in mitochondrial CYB gene of respiratory chain across different amphibian groups namely orders anura, urodela and gymnophiona. We observed that CUB was low in CYB gene of amphibia. The gymnophionans had comparatively high bias followed by urodeles and anurans. The codons namely TCA, CCA, CAA, CGA, TGA, AAA and ACA were over-represented in all three orders. The codons such as GCC and TCC were over-represented in anura whereas in urodela, the over-represented codons were TTA, CTA, ATA, GTA, GAA, GGA and GCA. In gymnophiona, GCC, TTA, CTA, ATA, GTA, GAA and GGA codons were over-represented. The regression analysis between effective number of codons (ENC) and nucleobase at the 3rd position revealed that nucleobase A and C influenced CUB positively in order anura, while in urodela and gymnophiona, nucleobase A and T influenced the CUB positively. Mutation pressure and natural selection mutually illustrate the CUB of CYB gene (complex III gene) of amphibia as elucidated by correlation analysis between 3rd nucleotide in a codon and overall nucleotide content of the gene. However, neutrality plot showed that natural selection was the dominant evolutionary factor of CUB.

Compositional properties and codon usage of TP73 gene family.

The TP73 gene is considered as one of the members of TP53 gene family and shows much homology to p53 gene. TP73 gene plays a pivotal role in cancer studies in addition to other biological functions. Codon usage bias (CUB) is the phenomenon of unequal usage of synonymous codons for an amino acid wherein some codons are more frequently used than others and it reveals the evolutionary relationship of a gene. Here, we report the pattern of codon usage in TP73 gene using various bioinformatic tools as no work was reported yet. Nucleotide composition analysis suggested that the mean nucleobase C was the highest, followed by G and the gene was GC rich. Correlation analysis between codon usage and GC3 suggested that most of the GC-ending codons showed positive correlation while most of the AT-ending codons showed negative correlation with GC3 in the coding sequences of TP73 gene variants in human. The CUB is moderate in human TP73 gene as evident from intrinsic codon deviation index (ICDI) analysis. Nature selected against two codons namely ATA (isoleucine) and AGA (arginine) in the coding sequences of TP73 gene during the course of evolution. A significant correlation (p < 0.05) was found between overall nucleotide composition and its composition at the 3rd codon position, indicating that both mutation pressure and natural selection might influence the CUB. The correlation analysis between ICDI and biochemical properties of protein suggested that variation of CUB was associated with degree of hydrophobicity and length of protein.

Analysis of codon usage patterns and influencing factors in Nipah virus.

Codon usage bias (CUB) is the unequal usage of synonymous codons of an amino acid in which some codons are used more often than others and is widely used in understanding molecular biology, genetics, and functional regulation of gene expression. Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes fatal disease in both humans and animals. NiV was first identified during an outbreak of a disease in Malaysia in 1998 and then occurred periodically since 2001 in India, Bangladesh, and the Philippines. We used bioinformatics tools to analyze the codon usage patterns in a genome-wide manner among 11 genomes of NiV as no work was reported yet. The compositional properties revealed that the overall GC and AT contents were 41.96 and 58.04%, respectively i.e. Nipah virus genes were AT-rich. Correlation analysis between overall nucleotide composition and its 3rd codon position suggested that both mutation pressure and natural selection might influence the CUB across Nipah genomes. Neutrality plot revealed natural selection might have played a major role while mutation pressure had a minor role in shaping the codon usage bias in NiV genomes.

Compositional features and codon usage pattern of TP63 gene.

The tumor protein p63encoded by the gene TP63 acts as a homologue of p53 protein. TP63 gene is the transformation factor with two initiation sites for transcriptional process and is related with stress, signal transduction and cell cycle control. The biasness in the preference of a few codons more frequently over other synonymous codons is the codon usage bias (CUB). Natural selection and mutational pressure are the two prime evolutionary forces acting on CUB. Here, the bioinformatic based analysis was performed to investigate the base distribution and CUB of TP63transcript variants (isoforms) as no work was performed earlier. Analysis of compositional features revealed variation in base content across TP63 gene isoforms and the GC content was more than 50%, indicating GC richness of its isoforms. The mean effective number of codons (ENC), a measure of CUB, was 51.83, i.e. overall CUB of TP63 gene was low. Among 13 isoforms of TP63 gene, nature selected against the CTA codon in 8 isoforms and favored five over-represented (RSCU > 1.6) codons namely CTG, CAG, ATC, AAC and GCC during evolution. Correlation between overall nucleotide composition and its 3rd codon position revealed that both mutational pressure and natural selection moulded its CUB. Further, the correlation between ENC and aromaticity depicted that variation of CUB was related to the degree of aromaticity of p63 protein.