Preserving condensate structure and composition by lowering sequence complexity.

Biomolecular condensates serve as pivotal mechanisms in cellular organization, often characterized by an abundance of intrinsically disordered proteins (IDPs) that undergo frequent mutations in their sequences. Despite this, IDP sequences exhibit non-random patterns, yet the precise relationship between these sequences and the emergent properties of condensates remains unclear. To address this gap, we propose a molecular theory that delineates how various sequence features of IDPs contribute to the organization and composition of condensates. This theory not only sheds light on the evolution of IDPs but also elucidates the emergence of non-random sequence patterns as essential elements for the formation of functional condensates. Correspondingly, we posit that the prevalence of low-complexity regions within IDPs is a result of evolutionary selection.