Understanding functional flexibility from intrinsic disorder landscapes of fourteen bat species proteomes

Despite the recognized significance of intrinsically disordered proteins (IDPs) in cellular processes and diseases, the landscape of intrinsic disorder within bat proteomes remains unexplored. Here, we systematically analyzed the prevalence and functional implications of IDPs across the complete proteomes of fourteen bat species and compared these to the human proteome. We first assessed ten widely used IDP predictors using a dataset of experimentally resolved disordered regions, identifying fIDPnn as the most suitable among the predictors benchmarked here for large-scale analyses of mammalian proteins. The results showed that the bat proteomes exhibit significantly lower IDP content (ranging from 12.6 % to 18.6 %) compared to humans (32.8 %). Correlation analyses revealed an inverse relationship between protein size and disorder content across both bats and humans. By integrating functional annotations with disorder contents, we found that intrinsic disorder enrichment or depletion in bat proteins aids in the species-specific immune gene regulation to coexist with a diverse array of pathogens. Our findings provide the first comprehensive map of intrinsic disorder in bat proteomes, highlighting distinct evolutionary and functional patterns relative to humans, and offer valuable insights into the molecular underpinnings of bat biology and their role as viral reservoirs.