Both Intrinsically Disordered Regions and Structural Domains Evolve Rapidly in Immune-Related Mammalian Proteins.

Eukaryotic proteins consist of structural domains (SDs) and intrinsically disordered regions (IDRs), i.e., regions that by themselves do not assume unique three-dimensional structures. IDRs are generally subject to less constraint and evolve more rapidly than SDs. Proteins with a lower number of protein-to-protein interactions (PPIs) are also less constrained and tend to evolve fast. Extracellular proteins of mammals, especially immune-related extracellular proteins, on average have relatively high evolution rates. This article aims to examine if a high evolution rate in IDRs or that in SDs accounts for the rapid evolution of extracellular proteins. To this end, we classified eukaryotic proteins based on their cellular localizations and analyzed them. Moreover, we divided proteins into SDs and IDRs and calculated the respective evolution rate. Fractional IDR content is positively correlated with evolution rate. For their fractional IDR content, immune-related extracellular proteins show an aberrantly high evolution rate. IDRs evolve more rapidly than SDs in most subcellular localizations. In extracellular proteins, however, the difference is diminished. For immune-related proteins in mammals in particular, the evolution rates in SDs come close to those in IDRs. Thus high evolution rates in both IDRs and SDs account for the rapid evolution of immune-related proteins.