Compositional Features and Codon Usage Pattern of Genes Associated with Parkinson's Disease.

Codon usage bias (CUB) is the phenomenon of non-uniform usage of synonymous codons in which some codons are more used than others and it helps in understanding the molecular organization of genome. Bioinformatic approach was used to analyze the protein-coding sequences of genes associated with Parkinson's disease (PD) to explore compositional features and codon usage pattern as no details work was reported yet. The average improved effective number of codons (Nc) and Nc prime were 42.74 and 44.26 respectively, indicated that CUB was low in these genes. In most of the genes, the overall GC content was almost 50% and GC content at the 1st codon position was the highest while GC content at the 2nd codon position was lowest. Relative synonymous codon usage (RSCU) analysis elucidated over-represented (p > 1.6) and under-represented codons (p < 0.6). The GTG (Val) is the only codon over-represented in all genes. Over-represented codons except (GTG) were A or T ending while under-represented codons (except ACT) were G or C ending. The codons namely TTA (Leu), CTA (Leu), ATC (Ile), ATA (Ile), AGT (Ser), AAC (Asn), TGT (Cys), TGC (Cys), CGC (Arg), AGA (Arg), and AGG (Arg) were absent in SNCA1 to SNCA8 genes. The codon TCG (Ser) was absent in all genes except UCHL1 and PINK1. Correspondence analysis (COA) revealed that the pattern of codon usage differs among genes associated with PD. Neutrality plot analysis indicated some of the points are diagonal distribution suggested that mutation pressure influenced the CUB in genes associated with PD.

Analysis of the Compositional Features and Codon Usage Pattern of Genes Involved in Human Autophagy.

Autophagy plays an intricate role in paradigmatic human pathologies such as cancer, and neurodegenerative, cardiovascular, and autoimmune disorders. Autophagy regulation is performed by a set of autophagy-related (ATG) genes, first recognized in yeast genome and subsequently identified in other species, including humans. Several other genes have been identified to be involved in the process of autophagy either directly or indirectly. Studying the codon usage bias (CUB) of genes is crucial for understanding their genome biology and molecular evolution. Here, we examined the usage pattern of nucleotide and synonymous codons and the influence of evolutionary forces in genes involved in human autophagy. The coding sequences (CDS) of the protein coding human autophagy genes were retrieved from the NCBI nucleotide database and analyzed using various web tools and software to understand their nucleotide composition and codon usage pattern. The effective number of codons (ENC) in all genes involved in human autophagy ranges between 33.26 and 54.6 with a mean value of 45.05, indicating an overall low CUB. The nucleotide composition analysis of the autophagy genes revealed that the genes were marginally rich in GC content that significantly influenced the codon usage pattern. The relative synonymous codon usage (RSCU) revealed 3 over-represented and 10 under-represented codons. Both natural selection and mutational pressure were the key forces influencing the codon usage pattern of the genes involved in human autophagy.

Gaining insights into the compositional constraints and molecular phylogeny of five silkworms mitochondrial genome.

This study was performed to identify codon usage bias (CUB), genetic similarity and phylogenetic analysis of complete mitochondrial genomes along with separate sequences of 13 protein coding genes per each genome from five types of silkworm including Bombyx mori, Bombyx mandarina, Samia cynthia ricini, Antheraea pernyi and Antheraea assama. Nucleotide composition analysis suggested that AT content was higher than GC content and t-test analysis revealed significance difference (p < 0.01) between AT and GC content. Relative synonymous CUB analysis revealed most over-represented codon ends with A or T. Parity plot analysis revealed both natural selection and mutation pressure influenced CUB of mitochondrial genes while neutrality plot analysis suggested that role of natural selection was higher than mutation pressure. The effective number of codons (ENC) revealed the CUB was low among genes and genomes. In phylogenetic analysis of complete mitochondrial genomes, the Bombyx mori fell in a same cluster with Bombyx mandarina and showed the most similarity (96.7%). In terms of protein coding genes, COX1, COX2 and COX3 showed the most obvious differences. In conclusion, comparative analysis of mitochondrial genomes could be used to identify differences in gene organization, accurate phylogenetic analysis and clustering of different types of silkworms.

Compositional features and pattern of codon usage for mitochondrial CO genes among reptiles.

The phenomenon of non-random occurrence of synonymous nucleotide triplets (codons) in the coding sequences of genes is the codon usage bias (CUB). In this study, we used bioinformatic tool kit to analyze the compositional pattern and CUB of mitogenes namely COI, COII and COIII across different orders of reptiles. Estimation of overall base composition in the protein-coding sequences of COI, COII and COIII genes of the reptilian orders revealed an uneven usage of nucleotides. The overall count of A nucleotide was found to be the highest while the overall count of G nucleotide was the least. The CO genes across the three reptilian orders were prominently AT biased. Comparison of the GC proportion at each codon position displayed that GC1 percentage ranked the highest in all the three CO genes of the reptilian orders. SCUO values indicated weaker CUB, while considerable variation of SCUO values existed in the three CO genes across the studied reptiles. Relative synonymous codon usage (RSCU) values indicated that mostly the A ending codons were preferred. Based on the parameters namely neutrality plot, mutational responsive index and translational selection, we could conclude that natural selection was the major evolutionary force in COI, COII and COIII genes in the studied reptilian orders. However, correspondence analysis, parity plot and correlation studies indicated the existence of mutation pressure as well on the CO genes.

Analysis of Codon Usage of Speech Gene FoxP2 among Animals.

The protein-coding gene FoxP2 (fork head box protein P2) plays a major role in communication and evolutionary changes. The present study carried out a comprehensive codon usage bias analysis in the FoxP2 gene among a diverse group of animals including fishes, birds, reptiles, and mammals. We observed that in the genome of fishes for the FoxP2 gene, codons ending with C or G were most frequently used, while in birds, reptiles, and mammals, codons ending with T or A were most frequently used. A higher ENC value was observed for the FoxP2 gene indicating a lower CUB. Parity role two-bias plots suggested that apart from mutation pressure, other factors such as natural selection might have influenced the CUB. The frequency distribution of the ENC observed and ENC expected ratio revealed that mutation pressure plays a key role in the patterns of codon usage of FoxP2. Besides, correspondence analysis exposed the composition of the nucleobase under mutation bias affects the codon usage of the FoxP2 gene. However, neutrality plots revealed the major role of natural selection over mutation pressure in the CUB of FoxP2. In addition, the codon usage patterns for FoxP2 among the selected genomes suggested that nature has favored nearly all the synonymous codons for encoding the corresponding amino acid. The uniform usage of 12 synonymous codons for FoxP2 was observed among the species of birds. The amino acid usage frequency for FoxP2 revealed that the amino acids Leucine, Glutamine, and Serine were predominant over other amino acids among all the species of fishes, birds, reptiles, and mammals.

Analysis of codon usage bias in mitochondrial CO gene among platyhelminthes.

The phenomenon of non-uniform usage of the synonymous codons, where some codons are given more preference to others, is known as codon usage bias (CUB). CUB is known to be determined by two major evolutionary forces i.e. mutation pressure and selection. We used various approaches to understand the codon usage pattern in mitochondrial CO (MT-CO) genes involved in complex IV of the respiratory chain (RC) as no work was reported yet. Our present study revealed that CUB was relatively high and the coding sequences were rich in A and T. Correspondence analysis further indicated that A/T compositional properties under mutational pressure might be affecting the codon usage pattern and was different in different classes for MT-CO gene. A highly significant correlation between A% and A3%, T% and T3%, G% and G3%, C% and C3%, GC% and GC3% in all the classes indicated that compositional constraints under mutational pressure and natural selection might affect the CUB. Neutrality plot indicated that both natural selection and mutational bias affected the CUB, where, natural selection played the major role as compared to mutational pressure.

Analysis of codon usage of Horseshoe Bat Hepatitis B virus and its host.

In the present analysis, codon usage strategies and base distribution of Horseshoe bat hepatitis B virus (HBHBV) were analyzed and compared with its host Rhinolophus sinicus, as no work was yet reported. The magnitude of synonymous codon usage bias (CUB) in the virus and its host was low with higher proportion of the base C. Notably, 21 more frequently used codons, 19 less frequently used codons and 3 underrepresented codons (TCG, ACG and GCG) were found to be similar in both virus and its host coding sequences. Neutrality plot analysis reported greater role of natural selection in HBHBV (67.84%) and R. sinicus (76.90%) over mutation pressure. Base skewness and protein properties also influenced the CUB of genes. Further, codon usage analysis depicted, HBHBV and R. sinicus had many similarities in codon usage patterns that might reflect viral adaptation to its host.

Free energy of mRNA positively correlates with GC content in chloroplast transcriptomes of edible legumes.

In the present study, the results of nucleotide composition analysis showed that the legume chloroplast (cp) transcriptomes were AT rich. From the neutrality plot, we observed that natural selection might have played a major role, while mutation pressure played a minor role in the CUB of cp transcriptomes. Highly significant (p < 0.05) negative correlation was found between mRNA free energy (mFE) and scaled chi-square for entire mRNA in Cicer arietinum and Lens culinaris suggesting that the release of higher energy by entire mRNA molecule might be associated with higher degree of codon usage bias in these two crop plants. Further, highly significant (p < 0.01, p < 0.05) positive correlation of mFE for entire mRNA was found with GC3 and that of mFE for 39 bases with GC, GC1, GC2 and GC3 contents among all the legumes. This indicated that higher GC content might induce the release of more free energy by cp transcriptomes.

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.

Composition, codon usage pattern, protein properties, and influencing factors in the genomes of members of the family Anelloviridae.

The present study was carried out on 62 genome sequences of members of the family Anelloviridae, as there have been no reports of genome analysis of these DNA viruses using a bioinformatics approach. The genes were found to be rich in AC content with low codon usage bias (CUB). Relative synonymous codon usage (RSCU) values identified the preferred codons for each amino acid in the family. The codon AGA was overrepresented, while the codons TCG, TTG, CGG, CGT, ACG, GCG and GAT were underrepresented in all of the genomes. A significant correlation was found between the effective number of codons (ENC) and base constraints, indicating that compositional properties might have influenced the CUB. A highly significant correlation was observed between the overall base content and the base content at the third codon position, indicating that mutations might have affected the CUB. A highly significant positive correlation was observed between GC12 and GC3 (r = 0.904, p < 0.01), which indicated that directional mutation pressure influenced all three codon positions. A neutrality plot revealed that the contribution of mutation and natural selection in determining the CUB was 58.6% and 41.4%, respectively.

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.

A Crosstalk on Codon Usage in Genes Associated with Leukemia.

Leukemia is the outcome of aggregation of damaged white blood cells. Several genes were reported to be associated with the pathogenesis of leukemia. These genes were computationally analyzed to decipher their codon usage bias (CUB) and to identify the prime factors influencing the codon usage profile as no work was reported yet. The mean values of synonymous codon usage order (SCUO) parameter indicated low CUB of the genes. Significant positive association of SCUO with overall GC and positional GCs might signal the presence of mutational pressure. However, neutrality plot suggested the dominant role of natural selection across the genes. Along with natural selection, the role of mutation pressure was also prominent and that might be responsible for lower CUB (SCUO = 0.19) of genes. Low translational speed might permit accuracy in the process. A strong inverse relationship of translational rate was observed with CUB of genes and folding energy.

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.

Analysis of mitochondrial protein-coding genes of Antheraea assamensis: Muga silkworm of Assam.

To understand the synonymous codon usage pattern in mitochondrial genome of Antheraea assamensis, we analyzed the 13 mitochondrial protein-coding genes of this species using a bioinformatic approach as no work was reported yet. The nucleotide composition analysis suggested that the percentages of A, T, G,and C were 33.73, 46.39, 9.7 and 10.17, respectively and the overall GC content was 19.86, that is, lower than 50% and the genes were AT rich. The mean effective number of codons of mitochondrial protein-coding genes was 36.30 and it indicated low codon usage bias (CUB). Relative synonymous codon usage analysis suggested overrepresented and underrepresented codons in each gene and the pattern of codon usage was different among genes. Neutrality plot analysis revealed a narrow range of distribution for GC content at the third codon position and some points were diagonally distributed, suggesting both mutation pressure and natural selection influenced the CUB.

Genome-wide analysis of codon usage pattern in herpesviruses and its relation to evolution.

The preferential use of a specific codon, out of a group of synonymous codons encoding the same amino acid, in a gene transcript results from the bias in codon choice. Various evolutionary forces namely mutation pressure and natural selection influence the pattern of codon usage i.e. distinct for each gene/genome. We investigated the pattern of codon usage of eight human herpesvirus genomes and compared them with two other herpesvirus genomes namely murine herpesvirus 68 and bovine herpesvirus type 1.1 to elucidate its compositional features, pattern of codon usage across the genomes and report the differences of codon usage pattern of human herpesviruses from that of other two other viruses. We also identified the similarity of the codon usage of human herpesviruses with its host (human). The genes were found to be CG rich in HHV2, HHV3, HHV4, HHV6, HHV7 and BH genomes while TA rich in HHV1, HHV5, HHV8 and MH genomes. The codon usage bias (CUB) of genes was low. A highly significant correlation was found among compositional contents depicting the role of mutational pressure along with natural selection in framing CUB. Several more frequently used codons as well as less frequently used codons were identified to be similar between each human virus and its host (human), while murine herpesvirus 68 and bovine herpesvirus type 1.1 genomes did not possess similar adaptation strategy as human herpesviruses to human (host), thus we could conclude that viral CUB might have been shaped as per their host's nature for better surveillance. Neutrality plot revealed mutational pressure mostly influenced the CUB of HHV1, HHV8 and MH viruses, while natural selection had a major impact in the CUB of HHV2, HHV3, HHV4, HHV5, HHV6, HHV7 and BH genomes.

Synonymous codon usage and context analysis of genes associated with pancreatic cancer.

Pancreatic cancer is a fatal disorder which originates in pancreas. Its mortality rate is increasing with time. Some studies also reported that pancreatic cancer would be ranked 2nd by the year 2030. Codon usage bias (CUB) arises when synonymous codons for each amino acid are not used randomly in the coding sequences of genes. We used bioinformatic methods to analyze the compositional properties, codon context and codon usage trend of the genes associated with pancreatic cancer as no work was reported yet. From the base composition analysis, the pancreatic cancer genes were found to be GC-rich and at the 3rd codon position the G/C ending codons were more preferred to A/T ending ones. The CUB was low in genes associated with pancreatic cancer. Correspondence analysis proposed that other than base constraints, CUB might also be affected by some other factors such as natural selection. Moreover, results of correlation analysis indicated that CUB and various GC contents i.e. GC, GC1, GC2, GC3 played important role in the release of free energy by transcripts of the genes associated with pancreatic cancer. The low compAI values of coding sequences suggested a low translation rate of the genes.

Analysis of codon usage bias of chloroplast genes in Oryza species : Codon usage of chloroplast genes in Oryza species.

MAIN CONCLUSION: The codon usage bias in chloroplast genes of Oryza species was low and AT rich. The pattern of codon usage was different among Oryza species and mainly influenced by mutation pressure and natural selection. Codon usage bias (CUB) is the unequal usage of synonymous codons in which some codons are more preferred to others in the coding sequences of genes. It shows a species-specific property. We studied the patterns of codon usage and the factors that influenced the CUB of protein-coding chloroplast (cp) genes in 18 Oryza species as no work was yet reported. The nucleotide composition analysis revealed that the overall GC content of cp genes in different species of Oryza was lower than 50%, i.e., Oryza cp genes were AT rich. Synonymous codon usage order (SCUO) suggested that CUB was weak in the cp genes of different Oryza species. A highly significant correlation was observed between overall nucleotides and its constituents at the third codon position suggesting that both, mutation pressure and natural selection, might influence the CUB. Correspondence analysis (COA) revealed that codon usage pattern differed across Oryza species. In the neutrality plot, a narrow range of GC3 distribution was recorded and some points were diagonally distributed in all the plots, suggesting that natural selection and mutation pressure might have influenced the CUB. The slope of the regression line was < 0.5, augmenting our inference that natural selection might have played a major role, while mutation pressure had a minor role in shaping the CUB of cp genes. The magnitudes of mutation pressure and natural selection on cp genes varied across Oryza species.

Codon usage pattern and its influencing factors for mitochondrial CO genes among different classes of Arthropoda.

Analysis of codon usage bias (CUB) is very much important in perceiving the knowledge of molecular biology, the discovery of a new gene, designing of transgenes and evolution of gene. In this study, we analyzed compositional features and codon usage of MT-CO (COI, COII and COIII) genes among the classes of Arthropoda to explore the pattern of CUB as no research work was reported yet. Nucleotide composition analysis in CO genes suggested that the genes were AT-rich in all the four classes of Arthropoda. CUB was low in all the classes of Arthropoda for MT-CO genes as revealed from a high effective number of codons (ENC). We also found that the evolutionary forces namely mutation pressure and natural selection were the key influencing factors in CUB among MT-CO genes as revealed by correlation analysis between overall nucleotide composition and nucleotide composition at the 3rd codon position. Correspondence analysis suggested that the pattern of CUB was different among the classes of Arthropoda. Further, it was revealed from the neutrality plot that natural selection had a dominant role while mutation pressure exhibited a minor role in structuring the pattern of codon usage in all the classes of Arthropoda across COI, COII and COIII genes.

Compositional Features and Codon Usage Pattern of Genes Associated with Anxiety in Human.

Codon usage bias (CUB) is the unequal usage of synonymous codon; some codons are more preferred than others. CUB analysis has applications in understanding the molecular organization of genome, genetics, gene expression, and molecular evolution. Bioinformatic approach was used to analyze the protein-coding sequences of genes involved in the anxiety to understand the patterns of codon usage as no work was reported yet. The improved effective number of codons (Nc) values ranged from 43.55 to 55.06, with a mean of 44.57, suggested that the overall CUB was low for genes associated with anxiety. The overall GC and AT content was 54.76 and 45.24, respectively. Relative synonymous codon usage (RSCU) analysis revealed that most frequently used codon ended mostly with C or G. The over-represented codons in genes associated with anxiety were CTG, ATC, GTG, AGC, ACC, and GCC, while under-represented codons were TTA, CTT, CTA, ATA, GTT, GTA, TCG, CCG, GCG, CAA, and CGT. Correlation analysis was performed between overall nucleotide composition and its 3rd codon positions, and observed highly significant (p < 0.01) correlation between them suggested that both mutation pressure and natural selection might affect the pattern of CUB. The highly significant correlation (0.598**, p < 0.01) was also observed between GC12 with GC3 suggested that directional mutation pressure might acted on all codon positions for genes associated with anxiety.

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.