Fig. 4.

Disorder-to-order transition and order-to-disorder transition on evolutionary time-scales. Disorder-to-order: a region from a hypothetical disordered protein becomes, e.g., preferentially stabilized, driving the equilibrium of the conformational ensemble towards solely the preferred conformation. The preferred conformation is further stabilized by mutations and becomes incrementally predominant. Over time, the region becomes ordered displaying only the predominant conformation. Order-to-disorder: a region from a hypothetical order protein starts to become more flexible, but is stabilized under certain conditions. Flexibility is beneficial and mutations to promote disorder accumulate, perhaps additional functions arise, and additional preferred conformations may become more predominant. Over time, the region becomes disordered, existing as a conformational ensemble