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A comprehensive in silico analysis of 71 species representing the different taxonomic classes and physiological genre of the domain Archaea was performed. These organisms differed in their physiological attributes, particularly oxygen tolerance and energy metabolism. We explored the diversity and similarity in the codon usage pattern in the genes and genomes of these organisms, emphasizing on their core cellular pathways. Our thrust was to figure out whether there is any underlying similarity in the design of core pathways within these organisms. Analyses of codon utilization pattern, construction of hierarchical linear models of codon usage, expression pattern and codon pair preference pointed to the fact that, in the archaea there is a trend towards biased use of synonymous codons in the core cellular pathways and the Nc-plots appeared to display the physiological variations present within the different species. Our analyses revealed that aerobic species of archaea possessed a larger degree of freedom in regulating expression levels than could be accounted for by codon usage bias alone. This feature might be a consequence of their enhanced metabolic activities as a result of their adaptation to the relatively O2-rich environment. Species of archaea, which are related from the taxonomical viewpoint, were found to have striking similarities in their ORF structuring pattern. In the anaerobic species of archaea, codon bias was found to be a major determinant of gene expression. We have also detected a significant difference in the codon pair usage pattern between the whole genome and the genes related to vital cellular pathways, and it was not only species-specific but pathway specific too. This hints towards the structuring of ORFs with better decoding accuracy during translation. Finally, a codon-pathway interaction in shaping the codon design of pathways was observed where the transcription pathway exhibited a significantly different coding frequency signature.

A comparative genomic analysis of three species of the soil bacterium Arthrobacter was undertaken with specific emphasis on genes involved in important and core energy metabolism pathways like glycolysis and amino acid metabolism. During the course of this study, it was revealed that codon bias of a particular species, namely Arthrobacter aurescens TC1, is significantly lower than that of the other two species A. chlorophenolicus A6 and Arthrobacter sp. FB24. The codon bias was also found to be negatively correlated with gene expression level which is determined by computing codon adaptation index of the genes. Uniformity in codon usage pattern among three species is evident in terms of genes which has high codon bias and multifunctional nature. Further, it was observed that this trend is present amongst the genes of important metabolic pathways, such as glycolysis and amino acid metabolism. The evolutionary divergence of the pathway gene sequences was calculated and was found to be equivalent in nature in the case of Arthrobacter sp. FB24 and Arthrobacter chlorophenolicus A6, but turned out to be dissimilar in the case of Arthrobacter aurescens TC1. A strong correlation between synonymous substitution rate and effective codon number or Nc was also observed. These observations clearly point out that the genes having low bias, in Arthrobacter aurescens TC1, and even of those that are part of highly conserved metabolic pathways like glycolysis and amino acid ensemble pathways have undergone a different type of evolution and might be subjected to positive selection pressure in comparison with Arthrobacter sp. FB24 and Arthrobacter chlorophenolicus A6.

The novel corona virus disease or COVID-19 caused by a positive strand RNA virus (PRV) called SARS-CoV-2 is plaguing the entire planet as we conduct this study. In this study a multifaceted analysis was carried out employing dinucleotide signature, codon usage and codon context to compare and unravel the genomic as well as genic characteristics of the SARS-CoV-2 isolates and how they compare to other PRVs which represents some of the most pathogenic human viruses. The main emphasis of this study was to comprehend the codon biology of the SARS-CoV-2 in the backdrop of the other PRVs like Poliovirus, Japanese encephalitis virus, Hepatitis C virus, Norovirus , Rubella virus, Semliki Forest virus, Zika virus, Dengue virus, Human rhinoviruses and the Betacoronaviruses since codon usage pattern along with the nucleotide composition prevalent within the viral genome helps to understand the biology and evolution of viruses. Our results suggest discrete genomic dinucleotide signature within the PRVs. Some of the genes from the different SARS-CoV-2 isolates were also found to demonstrate heterogeneity in terms of their dinucleotide signature. The SARS-CoV-2 isolates also demonstrated a codon context trend characteristically dissimilar to the other PRVs. The findings of this study are expected to contribute to the developing global knowledge base in countering COVID-19.

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