Estimated site-specific variation.

<p>The entropy-based variability over sites of (A) 10217 nucleotides and (B) 3392 amino acid residues was analysed using the DAMBE program. X axis: (A) nucleotide position; (B) amino acid position. Y axis: entropy value. Window sizes of 20 and 1 were used in the nucleotide and aa analyses, respectively. (C) Site-specific selection detection. Normalised dN-dS values were plotted for each codon site. (D) Epistatic interaction among DENV-1 codon sequences. In the above graph depicting the codon regions, each square node represents a residue position in the DENV1 codon sequence that participates in at least one interaction. The arrows (edges) representing those interactions are annotated with the fraction of graphs sampled in the chain sample that contains the edge. The analysis reports edges with marginal posterior probabilities (PP) exceeding a default cutoff of 0.5. These data are shown as PP{→}/PP{↔}/PP{←} beside the arrow, which indicates the direction. Both (C) and (D) were performed using the HyPhy software package. (E) Comparison of predicted three-dimensional residue substitution structures in (Left) PrM and (Right) NS3 proteins. The Mochizuki strain, a prototype DENV-1 strain, was used as a template for structural comparison. The wild-type (green) and substitution variant (blue) structures in the figure are aligned and oriented such that the substitution sites are positioned at the top. The substitution sites are highlighted in darker colours. The side chains of substitutions in the PrM¹⁰⁷ and NS3²⁵⁵ are shown. For each substitution, the magnified view (closed box on the right) is oriented for a clear depiction of conformational change due to substitution. An additional magnified surface view of NS3²⁵⁵ is shown on the lower right.