| Most proteins contain conformationally flexible regions (CFRs) causing proteins to have conformational ensembles (CE). Through conformational selection, the CE equilibrium responds to changes in the environment. The CE also depends on the protein sequence. We hypothesized that sequence divergence could result in lineage-specific patterns of CFRs, causing mutation-driven conformational selection and biological divergence. Using structural disorder prediction to identify CFRs and phylogenetic information, two different studies towards this hypothesis were conducted. First, the evolutionary dynamics of CFRs were investigated across flaviviruses. It was found that CFRs in flaviviruses undergo rapid disorder-to-order transitions that could lead to biological divergence. Second, the distribution of structural disorder across the tree of life was investigated. Disorder was investigated in eukaryotes and in prokaryotes with predicted changes in disordered positions observed. The results suggest that mutation-driven conformational selection is consistent with observations. |
