Arif Uddin

Codon usage bias and phylogenetic analysis of mitochondrial ND1 gene in pisces, aves, and mammals

Abstract The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters. The codon usage bias of MT-ND1 was low but the expression level was high as revealed from high ENC and CAI value. Correspondence analysis (COA) suggests that the pattern of codon usage for MT-ND1 gene is not same across species and that compositional constraint played an important role in codon usage pattern of this gene among pisces, aves, and mammals. From the regression equation of GC12 on GC3, it can be inferred that the natural selection might have played a dominant role while mutation pressure played a minor role in influencing the codon usage patterns. Further, ND1 gene has a discrepancy with cytochrome B (CYB) gene in preference of codons as evident from COA. The codon usage bias was low. It is influenced by nucleotide composition, natural selection, mutation pressure, length (number) of amino acids, and relative dinucleotide composition. This study helps in understanding the molecular biology, genetics, evolution of MT-ND1 gene, and also for designing a synthetic gene.

miRNAs and ovarian cancer: An overview†

Ovarian cancer (OC) is the sixth most common cancer in women globally. However, even with the advances in detection and therapeutics it still represents the most dangerous gynecologic malignancy in women of the industrialized countries. The discovery of micro‐RNAs (miRNA), a small noncoding RNA molecule targeting multiple mRNAs and regulation of gene expression by triggering translation repression and/or RNA degradation, has revealed the existence of a new array for regulation of genes involved in cancer. This review summarizes the current knowledge regarding the role of miRNAs expression in OC. It also provides information about potential clinical relevance of circulating miRNAs for OC diagnosis, prognosis, and therapeutics. The identification of functional targets for miRNAs represents a major obstacle in our understanding of microRNA function in OC, but significant progress is being made. The better understanding of the role of microRNA expression in ovarian cancer may provide new array for the detection, diagnosis, and therapy of the OC.

Factors influencing codon usage of mitochondrial ND1 gene in pisces, aves and mammals

Animal mitochondrial genome harbours 13 protein coding genes which regulate the process of respiration. The mitochondrial NADH dehydrogenase 1 (MT-ND1) gene, one of the 13 protein-coding genes, encodes the NADH dehydrogenase 1 enzyme of the respiratory chain. Analysis of codon usage bias (CUB) acquires importance for better understanding of the molecular biology, new gene discovery, design of transgenes and gene evolution. The MT-ND1 gene seems to be a good candidate for analyzing codon usage pattern, since no work has yet been reported. Moreover, it is still not clear which factors significantly influence the codon usage pattern. In the present study, comparative analysis of codon usage pattern, expression level and influencing factors for MT-ND1 gene from 100 different species each of pisces, aves and mammals were used for CUB analysis. Our result suggests that the gene is AT rich in pisces, aves and mammals and most of the nucleotides significantly differ among them as revealed from t-test. CUB was not remarkable as reflected by high value of effective number of codons and it also significantly differs among pisces, aves and mammals. Although we found that CUB is mainly influenced by natural selection and mutation pressure for MT-ND1 gene as suggested by correlation and correspondence analysis but neutrality plot further revealed that natural selection played a major role and mutation pressure played a minor role in codon usage pattern. Additionally, t-test analysis showed that the MT-ND1 gene has a wide significant discrepancy in codon choices in pisces, aves and mammals. This study has contributed to boost our understanding about the mechanism of distribution of the codons and the factors that may influence the evolution of the MT-ND1 gene.

Codon usage bias and its influencing factors for Y-linked genes in human

The non-uniform usage of synonymous codons during translation of a protein is the codon usage bias and is mainly influenced by natural selection and mutation pressure. We have used bioinformatic approaches to analyze codon usage bias of human Y-linked genes. Effective number of codon (ENC) suggested that the overall extent of codon usage bias of genes was low. The relative synonymous codon usage (RSCU) analysis revealed that AGA and CTG codons were over-represented in Y-linked genes. Compositional constraint under mutation pressure influenced the codon usage pattern as revealed by the correspondence analysis (COA). Parity plot suggests that both natural selection and mutation pressure might have influenced the codon usage bias of Y-linked genes.

Role of miRNAs in lung cancer

Lung cancer (LC) is the leading cause of cancer-related deaths all over the world, among both men and women, with an incidence of over 200,000 new cases per year coupled with a very high mortality rate. LC comprises of two major clinicopathological categories: small-cell (SCLC) and nonsmall-cell lung carcinoma (NSCLC). The microRNAs (miRNAs) are small noncoding RNAs, usually 18-25 nucleotides long, which repress protein translation through binding to complementary target mRNAs. The miRNAs regulate many biological processes including cell cycle regulation, cellular growth, proliferation, differentiation, apoptosis, metabolism, neuronal patterning, and aging. This review summarizes the role of miRNAs expression in LC. It also provides information about the miRNAs as biomarker and therapeutic target for lung cancer. Understanding the role of miRNAs in LC may provide insights into the diagnosis and treatment strategy for LC.

Nucleotide composition and codon usage bias of SRY gene

The SRY gene is present within the sex‐determining region of the Y chromosome which is responsible for maleness in mammals. The nonuniform usage of synonymous codons in the mRNA transcript for encoding a particular amino acid is the codon usage bias (CUB). Analysis of codon usage pattern is important to understand the genetic and molecular organisation of a gene. It also helps in heterologous gene expression, design of primer and synthetic gene. However, the analysis of codon usage bias of SRY gene was not yet studied. We have used bioinformatic tools to analyse codon usage bias of SRY gene across mammals. Codon bias index (CBI) indicated that the overall extent of codon usage bias was weak. The relative synonymous codon usage (RSCU) analysis suggested that most frequently used codons had an A or C at the third codon position. Compositional constraint played an important role in codon usage pattern as evident from correspondence analysis (CA). Significant correlation among nucleotides constraints indicated that both mutation pressure and natural selection affect the codon usage pattern. Neutrality plot suggested that natural selection might play a major role, while mutation pressure might play a minor role in codon usage pattern in SRY gene in different species of mammals.

Codon Usage Pattern of Genes Involved in Central Nervous System

Codon usage bias (CUB) is the non-uniform usage of synonymous codons in which some codons are more preferred to others in the transcript. Analysis of codon usage bias has applications in understanding the basics of molecular biology, genetics, gene expression, and molecular evolution. To understand the patterns of codon usage in genes involved in the central nervous system (CNS), we used bioinformatic approaches to analyze the protein-coding sequences of genes involved in the CNS. The improved effective number of codons (ENC) suggested that the overall codon usage bias was low. The relative synonymous codon usage (RSCU) revealed that the most frequently occurring codons had a G or C at the third codon position. The codons namely TCC, AGC, CTG, CAG, CGC, ATC, ACC, GTG, GCC, GGC, and CGG (average RSCUu2009>u20091.6) were over-represented. Both mutation pressure and natural selection might affect the codon usage pattern as evident from correspondence and parity plot analyses. The overall GC content (59.93) was higher than AT content, i.e., genes were GC-rich. The correlation of GC12 with GC3 suggested that mutation pressure might affect the codon usage pattern.

Preference of A/T ending codons in mitochondrial ATP6 gene under phylum Platyhelminthes: Codon usage of ATP6 gene in Platyhelminthes

Unequal usage of synonymous codons in the gene transcript for an amino acid is known as codon usage bias (CUB). It is a unique property of gene as well as genome. Mutation and natural selection are known to be the major factors that influence CUB. Other factors encompass gene expression level, GC content, codon position, recombination rate, RNA stability and gene length. CUB analysis helps in in-depth understanding of the molecular biology, genetics and genome evolution in a species. We used bioinformatic methods to explore the pattern of CUB in MT-ATP6 gene in different classes of platyhelminthes. The analysis is based on genetic code of translational table 14 of National Center of Biotechnology Information (NCBI) where the codon AAA codes for asparagine and TAA for tyrosine amino acid. The synonymous codon usage order (SCUO), an index of CUB, values in different classes namely cestoda, monogenea, rabditophora, trematoda and turbellaria of platyhelminths were found to be 0.43, 0.32, 0.49, 0.40 and 0.36, respectively which suggest that the codon usage bias of ATP6 gene was low (SCUOu2009<u20090.50). Highly significant correlation (pu2009<u20090.001) was found between SCUO and various GC contents indicating that GC composition had an influence on CUB. From the relative synonymous codon usage (RSCU) analysis on codons, we found most of the over-represented codons in all the classes were A/T ending types, which suggested that the preferred codons were influenced by compositional constraints. The PR2 plot revealed asymmetric usage of AT and GC bases among the four fold degenerate codon families with greater usage of G and T over A and C. Highly significant correlation (pu2009<u20090.001) was found between overall nucleotide composition and its 3rd codon position suggesting that both natural selection and mutation pressure might have influenced the CUB among different classes. Neutrality analysis revealed that natural selection might play a major role. Mutational responsive index (MRI) and translational selection (P2) values elucidated that selection for translational efficiency moderately affected the codon usage bias in MT-ATP6 gene.

Analysis of codon usage pattern of mitochondrial protein-coding genes in different hookworms

The phenomenon of unequal usage of synonymous codons encoding an amino acid in which some codons are more preferred to others is the codon usage bias (CUB) and it is species specific. Analysis of CUB helps in understanding evolution at molecular level and acquires significance in mRNA translation, design of transgenes and new gene discovery. In our current study, we analyzed synonymous codon usage pattern and the factors influencing it on mitochondrial protein coding genes of 6 different hookworms i.e. Ancylostoma ceylanicum, Ancylostoma duodenale, Necator americanus, Ancylostoma tubaeforme, Ancylostoma caninum and Uncinaria sanguinis as no work was reported yet. The effective number of codons for mitochondrial genes suggested that codon usage bias was high in most species. The GC content was lower than AT content i.e. genes were AT rich as indicated by nucleotide composition analysis. The overall nucleotide composition along with its composition at 3rd codon position and correspondence analysis suggested that both natural selection and mutation pressure might have affected the codon usage bias in mitochondrial genes. However, neutrality plot revealed that mutation pressure might have played a major role in A. ceylanicum while natural selection might have played the dominant role in Ancylostoma duodenale, Necator americanus, Ancylostoma tubaeforme, Ancylostoma caninum and Uncinaria sanguinis.

Transcript free energy positively correlates with codon usage bias in mitochondrial genes of Calypogeia species (Calypogeiaceae, Marchantiophyta)

Abstract The present study attempts to focus on the pattern of codon usage bias (CUB) in mitochondrial genes among four species of Calypogeia viz. C. arguta, C. integristipula, C. neogaea and C. suecica along with the factors influencing their CUB as no work was reported yet. The four taxa exhibit noticeable difference in their morphological features, habitat preference and growth forms. To understand the patterns of codon usage in Calypogeia mitochondrial genomes, we used bioinformatic tools to analyze the mitochondrial protein-coding sequences of four Calypogeia. In our current study, the mean nucleobase T was the highest while G was the lowest in all four species. The overall GC content was higher than AT content i.e. genes were AT rich. The CUB was low in mitochondrial genes of C. arguta, C. integristipula, C. neogaea and C. suecica, respectively as revealed from low synonymous codon usage order (SCUO) values. Heat map study revealed that most of the GC and AT ending codons showed positive correlations between codon usage and GC3. From the neutrality plot, the slope of the regression line indicated that natural selection might have played a major role over mutation pressure in shaping the CUB of mitochondrial genes in these four taxa. Highly significant (pu2009<u2009.01) correlation was found between mRNA free energy (mFE) and SCUO for entire mRNA which suggested that the release of higher energy by entire mRNA is associated with higher degree of codon usage bias. Further, highly significant (pu2009<u2009.01) negative correlation of mFE for entire mRNA was found with GC, GC1, GC2 and GC3 in all the four taxa. This indicated that higher GC content might have induced the release of lesser energy by mRNA molecules.