Evolution of intrinsic disorder in the structural domains of viral and cellular proteomes

Abstract Intrinsically disordered regions are flexible regions that complement the typical structured regions of proteins. Little is known however about their evolution. Here we leverage a comparative and evolutionary genomics approach to analyze intrinsic disorder in the structural domains of thous...

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Bibliographic Details
Main Authors: Fizza Mughal, Gustavo Caetano-Anollés
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-86045-4
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Summary:Abstract Intrinsically disordered regions are flexible regions that complement the typical structured regions of proteins. Little is known however about their evolution. Here we leverage a comparative and evolutionary genomics approach to analyze intrinsic disorder in the structural domains of thousands of proteomes. Our analysis revealed that viral and cellular proteomes employ similar strategies to increase disorder but achieve different goals. Viral proteomes evolve disorder for economy of genomic material and multifunctionality. On the other hand, cellular proteomes evolve disorder to advance functionality with increasing genomic complexity. Remarkably, phylogenomic analysis of intrinsic disorder showed that ancient domains were ordered and that disorder evolved as a benefit acquired later in evolution. Evolutionary chronologies of domains indexed with disorder levels and distributions across Archaea, Bacteria, Eukarya and viruses revealed six evolutionary phases, the oldest two harboring only ordered and moderate disorder domains. A biphasic spectrum of disorder versus proteome makeup captured the dichotomy in the evolutionary trajectories of viral and cellular ancestors, one following reductive evolution driven by viral spread of molecular wealth and the other following expansive evolutionary trends to advance functionality through massive domain-forming co-option of disordered loop regions.
ISSN:2045-2322