Base distribution in Dengue nucleotide sequences differs significantly from other mosquito-borne human-infecting flavivirus members

Introduction: Among the mosquito-borne human-infecting flavivirus species that include Zika, West Nile, yellow fever, Japanese encephalitis and Dengue viruses, the Zika virus is found to be closest to Dengue virus, sharing the same clade in the Flavivirus phylogenetic tree. We consider these five flaviviruses and on closer examination in our analyses, the nucleotide sequences of the Dengue viral genes (envelope and NS5) and genomes are seen to be quite widely different from the other four flaviviruses. We consider the extent of this distinction and determine the advantage and/or disadvantage such differences may confer upon the Dengue viral pathogenesis. Methods: We have primarily used a 2D graphical representation technique to show the differences in base distributions in these five flaviviruses and subsequently, obtained quantitative estimates of the differences. Similarity/dissimilarity between the viruses based on the genes were also determined which showed that the differences with the Dengue genes are more pronounced. Results: We found that the Dengue viruses compared to the other four flaviviruses spread rapidly worldwide and became endemic in various regions with small alterations in sequence composition relative to the host populations as revealed by codon usage biases and phylogenetic examination. Conclusion: We conclude that the Dengue genes are indeed more widely separated from the other aforementioned mosquito-borne human-infecting flaviviruses due to excess adenine component, a feature that is sparse in the literature. Such excesses have a bearing on drug and vaccine, especially peptide vaccine, development and should be considered appropriately.