Supriyo Chakraborty

Interplay between miRNAs and human diseases

MicroRNAs (miRNAs) are endogenous, non‐coding RNAs, which have evoked a great deal of interest due to their importance in many aspects of homeostasis and diseases. MicroRNAs are stable and are essential components of gene regulatory networks. They play a crucial role in healthy individuals and their dysregulations have also been implicated in a wide range of diseases, including diabetes, cardiovascular disease, kidney disease, and cancer. This review summarized the current understanding of interactions between miRNAs and different diseases and their role in disease diagnosis and therapy.

Codon usage trend in mitochondrial CYB gene

Here we reported the pattern of codon usage and the factors which influenced the codon usage pattern in mitochondrial cytochrome B (MT-CYB) gene among pisces, aves and mammals. The F1 axis of correspondence analysis showed highly significant positive correlation with nucleobases A3, C and C3 and significant negative correlation with T and T3 while F2 of correspondence analysis showed significant positive correlation with C and C3 and significant negative correlation with A and A3. From the neutrality plot, it was evident that the GC12 was influenced by mutation pressure and natural selection with a ratio of 0.10/0.90=0.11 in pisces, 0.024/0.976=0.0245 in aves and in mammals 0.215/0.785=0.273, which indicated that the role of natural selection was more than mutation pressure on structuring the bases at the first and second codon positions. Natural selection played the major role; but compositional constraint and mutation pressure also played a significant role in codon usage pattern. Analysis of codon usage pattern has contributed to the better understanding of the mechanism of distribution of codons and the evolution of MT-CYB gene.

Synonymous codon usage pattern in mitochondrial CYB gene in pisces, aves, and mammals

Abstract Cytochrome b (CYB) protein plays an important role in complex III of the mitochondrial oxidative phosphorylation. Codon usage is the phenomenon of non-uniform usage of synonymous codons. In the present study, we report the pattern of codon usage in MT-CYB gene using various codon usage parameters. Nucleotide composition such as % of C and T was higher than A and G in pisces. In aves, % of A and C was higher than T and G but in mammals, A and T was higher than C and G. Heat map shows that AT-ending codons were mostly negative and GC-ending codons were mostly positive. From the heat map based on RSCU values, it is evident that codon usage prefers A/C at the third codon position and it was less towards T/G in its third codon position. The codons absent in pisces were AGT (except Toxotes chatareus), TGT, and CAG (except Elasma zonatum). The codons such as AGT (except Falco peregrinus), CGT (except Vidua chalybeata), and ACG (except Aythya americana) were absent in aves whereas, in mammals, the absent codons were namely CAG (except Canis familiaris) and ACG (except Rattus norvegicus). Codon usage bias was low in pisces, aves, and mammals. The frequency of leucine was the highest in the amino acid and cysteine was the lowest. Correlation analysis further suggests that mutation pressure is mainly responsible for codon usage pattern. Natural selection might also play a vital role in codon usage pattern but it was weaker than mutation pressure.

Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species

TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

Codon usage pattern in human SPANX genes.

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.

Expression levels and codon usage patterns in nuclear genes of the filarial nematode Wucheraria bancrofti and the blood fluke Schistosoma haematobium

Synonymous codons are used with different frequencies, a phenomenon known as codon bias, which exists in many genomes and is mainly resolute by mutation and selection. To elucidate the genetic characteristics and evolutionary relationship of Wucheraria bancrofti and Schistosoma haematobium we examined the pattern of synonymous codon usage in nuclear genes of both the species. The mean overall GC contents of W. bancrofti and S. haematobium were 43.41 and 36.37%, respectively, which suggests that genes in both the species were AT rich. The value of the High Effective Number of Codons in both species suggests that codon usage bias was weak. Both species had a wide range of P3 distribution in the neutrality plot, with a significant correlation between P12 and P3. The codons were closer to the axes in correspondence analysis, suggesting that mutation pressure influenced the codon usage pattern in these species. We have identified the more frequently used codons in these species, most codons ending with an A or T. The nucleotides A/T and C/G were not proportionally used at the third position of codons, which reveals that natural selection might influence the codon usage patterns. The regression equation of P12 on P3 suggests that natural selection might have played a major role, while mutational pressure played a minor role in codon usage pattern in both species. These results form the basis of exploring the evolutionary mechanisms and the heterologous expression of medically important proteins of W. bancrofti and S. haematobium.

Codon bias and gene expression of mitochondrial ND2 gene in chordates

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 3rd 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 MTND2 gene is not associated with expression level. Mutation pressure and natural selection affect the codon usage pattern in MT-ND 2 gene.

Computational prediction of submergence responsive microRNA and their binding position within the genome of Oryza sativa.

Background: MicroRNAs (miRNAs) are small noncoding RNAs which play crucial role in response to the adverse biotic and abiotic stress conditions at the post transcriptional level. The functions of the miRNAs are generally based on complementarity to their target region. Results: We used the online tool psRNA Target for the identification of submergence responsive miRNA using the gene expression profile related to the submergence condition. We wrote a perl script for the prediction of miRNA target gene. The position based feature of the script increases the overall specificity of the program. Our perl script performed well on the genomic data of Oryza sativa and produced significant results with their positions. These results were analyzed on the basis of complementarity and the statistical scores are used to find out the most probable binding regions. These predicted binding regions are aligned with their respective miRNAs to find out the consensus sequence. We scored the alignment using a position dependent, mismatch penalty system. We also identified the rate of conservation of bases at a particular position for all the predicted binding regions and it was found that all the predicted binding regions maintain above 70% rate of conservation of bases. Conclusion: Our approach provides a novel framework for screening the genome of Oryza sativa. It can be broadly applied to identify complementarity specific miRNA targets computationally by doing a little modification of the script depending on the type of the miRNA.

Prediction of gene expression and codon usage in human parasitic helminths

AbstractnCodon usage bias refers to the differences in the occurrence frequency of synonymous codons. To understand the patterns of codon usage in mitochondrial genes we used bioinformatic approaches to analyze the protein coding sequences of W. bancrofti and S. haematobium as no work was reported earlier. It was found that the ENC value ranged from 43 to 60 with a mean of 46.91 in W. bancrofti but varied from 49 to 60 with a mean of 45.17 in S. haematobium, respectively. In W. bancrofti a significant positive correlation was found between ENC and GC3% (rxa0=xa00.826**, pxa0<xa00.01), but in S. haematobium significant correlation was found between ENC and GC3% (rxa0=xa00.983**, pxa0<xa00.01). Principal component analysis suggests that the pattern of codon usage significantly differed between W. bancrofti and S. haematobium. Neutrality plot reveals that natural selection played a major role while mutation pressure played a minor role in codon usage pattern in the mitochondrial protein coding genes of W. bancrofti and S. haematobium. Various factors namely nucleotide composition, natural selection and mutation pressure affected the codon usage pattern.

Codon usage pattern and prediction of gene expression level in Bungarus species

Codon bias study in an organism gains significance in understanding the molecular mechanism as well as the functional conservation of gene expression during the course of evolution. The prime focus in this study is to compare the codon usage patterns among the four species belonging to the genus Bungarus (B. multicinctus, B. fasciatus, B. candidus and B. flaviceps) using several codon bias parameters. Our results suggested that relatively low codon bias exists in the coding sequences of the selected species. The compositional constraints together with gene expression level might influence the patterns of codon usage among the genes of Bungarus species. Both natural selection and mutation pressure affect the codon usage pattern in Bungarus species as evident from correspondence analysis. Neutrality plot indicates that natural selection played a major role while mutation pressure played a minor role in codon usage pattern of the genes in Bungarus species.