Mutations in disordered proteins as early indicators of nucleic acid changes triggering speciation

Intrinsically disordered proteins are characterized by unusual sequence composition, structural flexibility, and functional spectra. These properties play an essential role in fostering protein evolution and in the formation of complex cellular pathways, especially in multicellular organisms. In this study, we analyze the role of different structural variants of proteins in speciation processes. Firstly, we separate human and mouse proteomes (taken as a reference) in three variants of disorder: ordered proteins (ORDPs), structured proteins with intrinsically disordered protein regions (IDPRs), and intrinsically disordered proteins (IDPs). Secondly, we compare the DNA divergence with the corresponding protein divergence, by confronting human and mouse coding sequences (separated in ORDPs, IDPRs, and IDPs) with their homologs from 26 eukaryotes. As a general rule, we find that IDPs phenotypically diverge earlier than ORDPs and IDPRs. ORDPs diverge later but are phenotypically more reactive to nucleotide mutations than IDPRs and IDPs. We suggest that IDPs may be involved in the early stages of the speciation process , likely connected to their functional spectra, mainly related to nucleic acid binding and transcription factors. In contrast, ORDPs may be essential in accelerating further phenotypic divergence.