Monisha Nath Choudhury

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.

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.

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.

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.

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.

Factors affecting the codon usage bias of SRY gene across mammals

Codon usage bias (CUB) is extensively found in a wide variety genomes and it is mostly affected by mutation pressure and natural selection. Analysis of CUB helps in studying the evolutionary features of a genome. The SRY gene plays an important role in male reproductive organ and a good candidate to study the evolutionary forces, since little work was reported earlier on this gene. We used bioinformatic methods to analyze the protein-coding sequences of SRY gene in 172 different mammalian species to understand the patterns of codon usage and the evolutionary forces acting on it. We found that the codon bias of SRY gene varies widely across mammals. Relative synonymous codon usage (RSCU) value revealed that the codons such as TCG, CCG, CAT, ATT, ACT, GCT, GTT, GCG, GGG and GGT were over-represented. Correspondence analysis indicated that the distribution of codons was more close to the axes indicating that compositional constraints might correlate to codon bias. Z-score analysis on RSCU values of codons identified a set of 11 codons viz. TCT, TTT, CTA, CTC, TAT, CAG, CGT, ATA, ACC, AAT and GTA which differed significantly at p<0.01 between 5% high and low gene expression datasets. Further, it was evident from the neutrality plot that GC12 was influenced by both mutation pressure and natural selection. From the study we concluded that natural selection played a dominant role, but mutational pressure played a minor role in the codon usage pattern of SRY gene across mammals.

Codon usage and expression level of human mitochondrial 13 protein coding genes across six continents

The study of codon usage coupled with phylogenetic analysis is an important tool to understand the genetic and evolutionary relationship of a gene. The 13 protein coding genes of human mitochondria are involved in electron transport chain for the generation of energy currency (ATP). However, no work has yet been reported on the codon usage of the mitochondrial protein coding genes across six continents. To understand the patterns of codon usage in mitochondrial genes across six different continents, we used bioinformatic analyses to analyze the protein coding genes. The codon usage bias was low as revealed from high ENC value. Correlation between codon usage and GC3 suggested that all the codons ending with G/C were positively correlated with GC3 but vice versa for A/T ending codons with the exception of ND4L and ND5 genes. Neutrality plot revealed that for the genes ATP6, COI, COIII, CYB, ND4 and ND4L, natural selection might have played a major role while mutation pressure might have played a dominant role in the codon usage bias of ATP8, COII, ND1, ND2, ND3, ND5 and ND6 genes. Phylogenetic analysis indicated that evolutionary relationships in each of 13 protein coding genes of human mitochondria were different across six continents and further suggested that geographical distance was an important factor for the origin and evolution of 13 protein coding genes of human mitochondria.

Gene expression, nucleotide composition and codon usage bias of genes associated with human Y chromosome

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 usage pattern of some codons like the SPANX genes in X chromosome.

Corrigendum to “Factors affecting the codon usage bias of SRY gene across mammals” [Gene 630C (2017) 13–20]

The authors regret Abstract Wrong: Relative synonymous codon usage (RSCU) value revealed that the codons such as TCG, CCG, CAT, ATT, ACT, GCT, GTT, GCG, GGG and GGT were over-represented. Right: Relative synonymous codon usage (RSCU) value revealed that the codons such as TCG, CCG, CAT, ATT, ACT, GTC, GTT, GCG, GGG and GGT were under-represented. Result Codon usage pattern of SRY gene across mammals Wrong: The codons namely TCG, CCG, CAT, ATT, ACT, GCT, GTT, GCG, GGG and GGT were over-represented (mean RSCU value> 1.6) in SRY gene across mammals under study (Fig. 2b). The codons namely AGC, ACA, GTG and GGA were under-represented (mean RSCU value< 0.6) (Fig. 2c). Right: The codons namely TCG, CCG, CAT, ATT, ACT, GTC, GTT, GCG, GGG and GGT were under-represented (mean RSCU value< 0.6) in SRY gene across mammals under study (Fig. 2b). The codons namely AGC, ACA, GTG and GGA were over-represented (mean RSCU value> 1.6) (Fig. 2c). Discussion Wrong: In our study, the pattern of codon usage bias differs in different species of mammals for SRY gene under study. The over-represented codons were TCG, CCG, CAT, ATT, ACT, GCT, GTT, GCG, GGG and GGT whereas under-represented codons were AGC, ACA, GTG and GGA. Right: In our study, the pattern of codon usage bias differs in different species of mammals for SRY gene under study. The under-represented codons were TCG, CCG, CAT, ATT, ACT, GTC, GTT, GCG, GGG and GGT whereas over-represented codons were AGC, ACA, GTG and GGA. The authors would like to apologise for any inconvenience caused.