Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID-19 cases: A challenging global threat with a special focus on the Indian subcontinent.

The emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 has resulted into a very massive surge in COVID-19 cases worldwide. Due to continuous emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has caused severe morbidity and mortality in last two years. The rate of infectivity of Omicron variant is much higher than Delta variant and in a very quick time Omicron has displaced the Delta variant and now become a dominant variant across the globe. The twin combination of Omicron and Delta variant is triggering a Tsunami wave of ever high surges in COVID-19 cases worldwide. This article highlights the global threats and challenges posed by Omicron, and strategies to counter it with a particular focus on Indian sub-continent.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic.

Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

Leucine encoding codon TTG shows an inverse relationship with GC content in genes involved in neurodegeneration with iron accumulation.

We determined various forces involved in shaping codon usage of the genes linked to brain iron accumulation and infantile neuroaxonal dystrophy. The analysis paved the way for determining the forces responsible for composition, expression level, physical properties and codon bias of a gene. An interesting observation related to composition was that, on all the three codon positions, any two of the four nucleotides had similar compositions. CpG, TpA, and GpT dinucleotides were underrepresented with the overrepresentation of TpG dinucleotide. CpG and TpA containing codons ATA, CTA, TCG, and GCG were underrepresented, while TpG dinucleotide containing codon CTG was overrepresented, indicative of compositional constraints importance. GC ending codons were favored when the genome is GC rich, except leucine encoding codon TTG, which exhibits an inverse relationship with GC content. Nucleotide disproportions are found associated with the physical properties of proteins. The values of CAI and ENc are suggestive of low codon bias in genes. Considering the results of neutrality analysis, parity analysis, underrepresentation of TpA and CpG codons, and over-representation of TpG codons, the correlation between the compositional constraints and skew relationships with protein properties suggested the role of all the three selectional, mutational and compositional forces in shaping codon usage with the dominance of selectional pressure.

Nutritional applications and beneficial health applications of green tea and l-theanine in some animal species: A review.

Green tea (Camellia sinensis) is a popular herbal plant with abundant health benefits, and thus, it has been used as a potent antioxidant for a long time. Based on the available literature, the diversity and the availability of multifunctional compounds in green tea offer its noteworthy potential against many diseases such as liver and heart diseases, inflammatory conditions and different metabolic syndromes. Owing to its bioactive constituents including caffeine, amino acids, l-theanine, polyphenols/flavonoids and carbohydrates among other potent molecules, green tea has many pharmacological and physiological effects. The effects of green tea include anti-oxidative, anti-inflammatory, anti-arthritic, anti-stress, hypolipidaemic, hypocholesterolaemic, skin/collagen protective, hepatoprotective, anti-diabetic, anti-microbial, anti-infective, anti-parasitic, anti-cancerous, inhibition of tumorigenesis and angiogenesis, anti-mutagenic, and memory and bone health-improving activities. Apart from its utilization in humans, green tea has also played a significant role in livestock production such as in dairy, piggery, goatry and poultry industries. Supplementation of animal feeds with green tea and its products is in line with the modern concepts of organic livestock production. Hence, incorporating green tea or green tea by-products into the diet of poultry and other livestock can enhance the value of the products obtained from these animals. Herein, an effort is made to extend the knowledge on the importance and useful applications of green tea and its important constituents in animal production including poultry. This review will be a guideline for researchers and entrepreneurs who want to explore the utilization of feeds supplemented with green tea and green tea by-products for the enhancement of livestock production.

Amantadine resistance among highly pathogenic avian influenza viruses (H5N1) isolated from India.

Emergence of antiviral resistance among H5N1 avian influenza viruses is the major challenge in the control of pandemic influenza. Matrix 2 (M2) inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) are the two classes of antiviral agents that are specifically active against influenza viruses and are used for both treatment and prophylaxis of influenza infections. Amantadine targets the M2 ion channel of influenza A virus and interrupts virus life cycle through blockade of hydrogen ion influx. This prevents uncoating of the virus in infected host cells which impedes the release of ribonucleoprotein required for transcription and replication of virion in the nucleus. The present study was carried out to review the status of amantadine resistance in H5N1 viruses isolated from India and to study their replicative capability. Results of the study revealed resistance to amantadine in antiviral assay among four H5N1 viruses out of which two viruses had Serine 31 Asparagine (AGT-AAT i.e., S31N) mutation and two had Valine 27 Alanine (GTT-GCT i.e., V27A) mutation. The four resistant viruses not only exhibited significant difference in effective concentration 50% (EC50) values of amantadine hydrochloride from that of susceptible viruses (P < 0.0001) but also showed significant difference between two different types (S31N and V27A) of mutant viruses (P < 0.05). Resistance to amantadine could also be demonstrated in a simple HA test after replication of the viruses in MDCK cells in presence of amantadine. The study identifies the correlation between in vitro antiviral assay and presence of established molecular markers of resistance, the retention of replicative capacity in the presence of amantadine hydrochloride by the resistant viruses and the emergence of resistant mutations against amantadine among avian influenza viruses (H5N1) without selective drug pressure.

Detection and molecular characterization of naturally transmitted sheep associated malignant catarrhal fever in cattle in India.

Malignant catarrhal fever (MCF) is a fatal herpesvirus infection of domestic and wild ruminants, with a short and dramatic clinical course characterized primarily by high fever, severe depression, swollen lymph nodes, salivation, diarrhea, dermatitis, neurological disorders, and ocular lesions often leading to blindness. In the present study, fatal clinical cases of sheep associated malignant catarrhal fever (SA-MCF) were identified in cattle in the state of Karnataka. These cases were initially presented with symptoms of diarrhea, respiratory distress, conjunctivitis, and nasal discharges. Laboratory diagnosis confirmed the detection of ovine herpesvirus-2 (OvHV-2) genome in the peripheral blood samples of two ailing animals. The blood samples collected subsequently from sheep of the neighboring areas also showed presence of OvHV-2 genome indicating a nidus of infection in the region. The positive test results were further confirmed by nucleotide sequencing of the OIE approved portion of tegument gene as well as complete ORF8 region of the OvHV-2 genome. Phylogenetic analysis based on the sequence of the latter region indicated close genetic relationship with other OvHV-2 reported elsewhere in the world.

Relative synonymous codon usage and codon pair analysis of depression associated genes.

Depression negatively impacts mood, behavior, and mental and physical health. It is the third leading cause of suicides worldwide and leads to decreased quality of life. We examined 18 genes available at the genetic testing registry (GTR) from the National Center for Biotechnological Information to investigate molecular patterns present in depression-associated genes. Different genotypes and differential expression of the genes are responsible for ensuing depression. The present study, investigated codon pattern analysis, which might play imperative roles in modulating gene expression of depression-associated genes. Of the 18 genes, seven and two genes tended to up- and down-regulate, respectively, and, for the remaining genes, different genotypes, an outcome of SNPs were responsible alone or in combination with differential expression for different conditions associated with depression. Codon context analysis revealed the abundance of identical GTG-GTG and CTG-CTG pairs, and the rarity of methionine-initiated codon pairs. Information based on codon usage, preferred codons, rare, and codon context might be used in constructing a deliverable synthetic construct to correct the gene expression level of the human body, which is altered in the depressive state. Other molecular signatures also revealed the role of evolutionary forces in shaping codon usage.

Molecular insights into codon usage analysis of mitochondrial fission and fusion gene: relevance to neurodegenerative diseases.

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.

Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.

Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders.

In-silico Codon Context and Synonymous Usage Analysis of Genes for Molecular Mechanisms Inducing Autophagy and Apoptosis with Reference to Neurodegenerative Disorders.

Background: Autophagy and apoptosis are cellular processes that maintain cellular homeostasis and remove damaged or aged organelles or aggregated and misfolded proteins. Stress factors initiate the signaling pathways common to autophagy and apoptosis. An imbalance in the autophagy and apoptosis, led by cascade of molecular mechanism prior to both processes culminate into neurodegeneration. Objective: In present study, we urge to investigate the codon usage pattern of genes which are common before initiating autophagy and apoptosis. Methods: In the present study, we took up eleven genes (DAPK1, BECN1, PIK3C3 (VPS34), BCL2, MAPK8, BNIP3 L (NIX), PMAIP1, BAD, BID, BBC3, MCL1) that are part of molecular signaling mechanism prior to autophagy and apoptosis. We analyzed dinucleotide odds ratio, codon bias, usage, context, and rare codon analysis. Results: CpC and GpG dinucleotides were abundant, with the dominance of G/C ending codons as preferred codons. Clustering analysis revealed that MAPK8 had a distinct codon usage pattern compared to other envisaged genes. Both positive and negative contexts were observed, and GAG-GAG followed by CTG-GCC was the most abundant codon pair. Of the six synonymous arginine codons, two codons CGT and CGA were the rarest. Conclusions: The information presented in the study may be used to manipulate the process of autophagy and apoptosis and to check the pathophysiology associated with their dysregulation.

A Synthetic Biology Approach for Vaccine Candidate Design against Delta Strain of SARS-CoV-2 Revealed Disruption of Favored Codon Pair as a Better Strategy over Using Rare Codons.

The SARS-CoV-2 delta variant (B.1.617.2) appeared for the first time in December 2020 and later spread worldwide. Currently available vaccines are not so efficacious in curbing the viral pathogenesis of the delta strain of COVID; therefore, the development of a safe and effective vaccine is required. In the present study, we envisaged molecular patterns in the structural genes' spike, nucleoprotein, membrane, and envelope of the SARS-CoV-2 delta variant. The study was based on determining compositional features, dinucleotide odds ratio, synonymous codon usage, positive and negative codon contexts, rare codons, and insight into relatedness between the human host isoacceptor tRNA and preferred codons from the structural genes. We found specific patterns, including a significant abundance of T nucleotide over all other three nucleotides. The underrepresentation of GpA, GpG, CpC, and CpG dinucleotides and the overrepresentation of TpT, ApA, CpT, and TpG were observed. A preference towards ACT- (Thr), AAT- (Asn), TTT- (Phe), and TTG- (Leu) initiated codons and aversion towards CGG (Arg), CCG (Pro), and CAC (His) was present in the structural genes of the delta strain. The interaction between the host tRNA pool and preferred codons of the envisaged structural genes revealed that the virus preferred the codons for those suboptimal numbers of isoacceptor tRNA were present. We see this as a strategy adapted by the virus to keep the translation rate low to facilitate the correct folding of viral proteins. The information generated in the study helps design the attenuated vaccine candidate against the SARS-CoV-2 delta variant using a synthetic biology approach. Three strategies were tested: changing TpT to TpA, introducing rare codons, and disrupting favored codons. It found that disrupting favored codons is a better approach to reducing virus fitness and attenuating SARS-CoV-2 delta strain using structural genes.

Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts.

Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.

Synonymous Codon Variant Analysis for Autophagic Genes Dysregulated in Neurodegeneration.

Neurodegenerative disorders are often a culmination of the accumulation of abnormally folded proteins and defective organelles. Autophagy is a process of removing these defective proteins, organelles, and harmful substances from the body, and it works to maintain homeostasis. If autophagic removal of defective proteins has interfered, it affects neuronal health. Some of the autophagic genes are specifically found to be associated with neurodegenerative phenotypes. Non-functional, mutated, or gene copies having silent mutations, often termed synonymous variants, might explain this. However, these synonymous variant which codes for exactly similar proteins have different translation rates, stability, and gene expression profiling. Hence, it would be interesting to study the pattern of synonymous variant usage. In the study, synonymous variant usage in various transcripts of autophagic genes ATG5, ATG7, ATG8A, ATG16, and ATG17/FIP200 reported to cause neurodegeneration (if dysregulated) is studied. These genes were analyzed for their synonymous variant usage; nucleotide composition; any possible nucleotide skew in a gene; physical properties of autophagic protein including GRAVY and AROMA; hydropathicity; instability index; and frequency of acidic, basic, neutral amino acids; and gene expression level. The study will help understand various evolutionary forces acting on these genes and the possible augmentation of a gene if showing unusual behavior.

Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities.

Introduction: Neurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes and pathways acting in opposition. Identifying and studying the genes simultaneously up or downregulated during morbidities helps curb both ailments together. Methods: This study examines four genes. Three of these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), and Cyclin E2 (CCNE2) are upregulated, and one protein phosphatase 2 phosphatase activator (PTPA) is simultaneously downregulated in both disorders. We investigated molecular patterns, codon usage, codon usage bias, nucleotide bias in the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context. Results: Parity analysis revealed that T is preferred over A, and G is preferred over C in the third codon position, suggesting composition plays no role in nucleotide bias in both the upregulated and downregulated gene sets and that mutational forces are stronger in upregulated gene sets than in downregulated ones. Transcript length influenced the overall %A composition and codon bias, and the codon AGG exerted the strongest influence on codon usage in both the upregulated and downregulated gene sets. Codons ending in G/C were preferred for 16 amino acids, and glutamic acid-, aspartic acid-, leucine-, valine-, and phenylalanine-initiated codon pairs were preferred in all genes. Codons CTA (Leu), GTA (Val), CAA (Gln), and CGT (Arg) were underrepresented in all examined genes. Discussion: Using advanced gene editing tools such as CRISPR/Cas or any other gene augmentation technique, these recoded genes may be introduced into the human body to optimize gene expression levels to augment neurodegeneration and cancer therapeutic regimens simultaneously.

An Insight into Codon Pattern Analysis of Autophagy Genes Associated with Virus Infection.

INTRODUCTION: Apoptosis and autophagy are the two fundamental processes involved in maintaining homeostasis, and a common stimulus may initiate the processes. Autophagy has been implicated in various diseases, including viral infections. Genetic manipulations leading to altered gene expression might be a strategy to check virus infection. AIM: Determination of molecular patterns, relative synonymous codon usage, codon preference, codon bias, codon pair bias, and rare codons so that genetic manipulation of autophagy genes may be done to curb viral infection. METHODS: Using various software, algorithms, and statistical analysis, insights into codon patterns were obtained. A total of 41 autophagy genes were envisaged as they are involved in virus infection. RESULTS: The A/T and G/C ending codons are preferred by different genes. AAA-GAA and CAG-CTG codon pairs are the most abundant codon pairs. CGA, TCG, CCG, and GCG are rarely used codons. CONCLUSION: The information generated in the present study helps manipulate the gene expression level of virus infection-associated autophagy genes through gene modification tools like CRISPR. Codon deoptimization for reducing while codon pair optimization for enhancing is efficacious for HO-1 gene expression.

Comparative Analysis of Published Database Predicting MicroRNA Binding in 3'UTR of mRNA in Diverse Species.

BACKGROUND: Micro-RNAs are endogenous non-coding RNA moieties of 22-27 nucleotides that play a crucial role in the regulation of various biological processes and make them useful prognostic and diagnostic biomarkers. Discovery and experimental validation of miRNA is a laborious and time-consuming process. For early prediction, multiple bioinformatics databases are available for miRNA target prediction; however, their utility can confuse amateur researchers in selecting the most appropriate tools for their study. OBJECTIVE: This descriptive review aimed to analyse the usability of the existing database based on the following criteria: accessibility, efficiency, interpretability, updatability, and flexibility for miRNA target prediction of 3'UTR of mRNA in diverse species so that the researchers can utilize the database most appropriate to their research. METHODS: A systematic literature search was performed in PubMed, Google Scholar and Scopus databases up to November 2022. ≥10,000 articles found online, including ⁓130 miRNA tools, which contain various information on miRNA. Out of them, 31 databases that provide information on validated 3'UTR miRNAs target databases were included and analysed in this review. RESULTS: These miRNA database tools are being used in varied areas of biological research to select the most suitable miRNA for their experimental validation. These databases, updated until the year 2021, consist of miRNA-related data from humans, animals, mice, plants, viruses etc. They contain 525-29806351 data entries, and information from most databases is freely available on the online platform. CONCLUSION: Reviewed databases provide significant information, but not all information is accurate or up-to-date. Therefore, Diana-TarBase and miRWalk are the most comprehensive and up-to-date databases.

Codon Usage Analysis of Pro-Apoptotic Bim Gene Isoforms.

BACKGROUND: Bim is a Bcl-2 homology 3 (BH3)-only proteins, a group of pro-apoptotic proteins involved in physiological and pathological conditions. Both the overexpression and under-expression of Bim protein are associated with the diseased condition, and various isoforms of Bim protein are present with differential apoptotic potential. OBJECTIVE: The present study attempted to envisage the association of various molecular signatures with the codon choices of Bim isoforms. METHODS: Molecular signatures like composition, codon usage, nucleotide skews, the free energy of mRNA transcript, physical properties of proteins, codon adaptation index, relative synonymous codon usage, and dinucleotide odds ratio were determined and analyzed for their associations with codon choices of Bim gene. RESULTS: Skew analysis of the Bim gene indicated the preference of C nucleotide over G, A, and T and preference of G over T and A nucleotides was observed. An increase in C content at the first and third codon position increased gene expression while it decreased at the second codon position. Compositional constraints on nucleotide C at all three codon positions affected gene expression. The analysis revealed an exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim. We correlated it with the requirement of rapid demethylation machinery to fine-tune the Bimgene expression. Also, mutational pressure played a dominant role in shaping codon usage bias in Bim isoforms. CONCLUSION: An exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim indicates a high order selectional force to fine tune Bim gene expression.

Codon Usage Bias Correlates With Gene Length in Neurodegeneration Associated Genes.

Codon usage analysis is a crucial part of molecular characterization and is used to determine the factors affecting the evolution of a gene. The length of a gene is an important parameter that affects the characteristics of the gene, such as codon usage, compositional parameters, and sometimes, its functions. In the present study, we investigated the association of various parameters related to codon usage with the length of genes. Gene expression is affected by nucleotide disproportion. In sixty genes related to neurodegenerative disorders, the G nucleotide was the most abundant and the T nucleotide was the least. The nucleotide T exhibited a significant association with the length of the gene at both the overall compositional level and the first and second codon positions. Codon usage bias (CUB) of these genes was affected by pyrimidine and keto skews. Gene length was found to be significantly correlated with codon bias in neurodegeneration associated genes. In gene segments with lengths below 1,200 bp and above 2,400 bp, CUB was positively associated with length. Relative synonymous CUB, which is another measure of CUB, showed that codons TTA, GTT, GTC, TCA, GGT, and GGA exhibited a positive association with length, whereas codons GTA, AGC, CGT, CGA, and GGG showed a negative association. GC-ending codons were preferred over AT-ending codons. Overall analysis indicated that the association between CUB and length varies depending on the segment size; however, CUB of 1,200-2,000 bp gene segments appeared not affected by gene length. In synopsis, analysis suggests that length of the genes correlates with various imperative molecular signatures including A/T nucleotide disproportion and codon choices. In the present study we additionally evaluated various molecular features and their correlation with different indices of codon usage, like the Codon Adaptation Index (CAI) and Relative Dynonymous Codon Usage (RSCU) of codons. We also considered the impact of gene fragment size on different molecular features in genes related to neurodegeneration. This analysis will aid our understanding of and in potentially modulating gene expression in cases of defective gene functioning in clinical settings.

An investigation of codon usage pattern analysis in pancreatitis associated genes.

BACKGROUND: Pancreatitis is an inflammatory disorder resulting from the autoactivation of trypsinogen in the pancreas. The genetic basis of the disease is an old phenomenon, and evidence is accumulating for the involvement of synonymous/non-synonymous codon variants in disease initiation and progression. RESULTS: The present study envisaged a panel of 26 genes involved in pancreatitis for their codon choices, compositional analysis, relative dinucleotide frequency, nucleotide disproportion, protein physical properties, gene expression, codon bias, and interrelated of all these factors. In this set of genes, gene length was positively correlated with nucleotide skews and codon usage bias. Codon usage of any gene is dependent upon its AT and GC component; however, AGG, CGT, and CGA encoding for Arg, TCG for Ser, GTC for Val, and CCA for Pro were independent of nucleotide compositions. In addition, Codon GTC showed a correlation with protein properties, isoelectric point, instability index, and frequency of basic amino acids. We also investigated the effect of various evolutionary forces in shaping the codon usage choices of genes. CONCLUSIONS: This study will enable us to gain insight into the molecular signatures associated with the disease that might help identify more potential genes contributing to enhanced risk for pancreatitis. All the genes associated with pancreatitis are generally associated with physiological function, and mutations causing loss of function, over or under expression leads to an ailment. Therefore, the present study attempts to envisage the molecular signature in a group of genes that lead to pancreatitis in case of malfunction.

Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia.

Dementia is a clinical syndrome characterized by progressive cognitive decline, and the symptoms could be gradual, persistent, and progressive. In the present study, we investigated 47 genes that have been linked to dementia. Compositional, selectional, and mutational forces were seen to be involved. Nucleotide components that influenced A- and GC-affected codon usages bias at all three codon positions. The influence of these two compositional constraints on codon usage bias (CUB) was positive for nucleotide A and negative for GC. Nucleotide A also experienced the highest mutational force, and GC-ending codons were preferred over AT-ending codons. A high bias toward GC-ending codons enhances the gene expression level, evidenced by the positive association between CAI- and GC-ending codons. Unusual behavior of the TTG codon showing an inverse relationship with the GC-ending codon and negative influence of gene expression, behavior contrary to all other GC-ending codons, shows an operative selectional force. Furthermore, parity analysis, higher translational selection value, preference of GC-ending codons over AT-ending codons, and association of gene length with gene expression refer to the dominant role of selection pressure with compositional constraint and mutational force-shaping codon usage.