Coevolved residues and the functional association for intrinsically disordered proteins.

The evolution of intrinsically disordered proteins has been studied primarily by focusing on evolutionary changes at an individual position such as substitution and conservation, but the evolutionary association between disordered residues has not been comprehensively investigated. Here, we analyze the distribution of residue-residue coevolution for disordered proteins. We reveal that the degree of coevolved residues significantly decreases in disordered regions regardless of the sequence propensity, and the degree distribution of coevolved and conserved residues exclusively differs in each functional category. Consequently, the coevolution information can be useful for predicting intrinsic disorder and understanding biological functions of a disordered region from the sequence.