Mutational destabilisation accelerates the evolution of novel sensory and network functions

Binding-induced folding1-4 (BIF) is a promising mechanism that can be used to rapidly convert binders into sensors/regulators without allosteric design. Here we showed that allosteric regulatory proteins AraC can acquire BIF mechanism without compromising their inherent allosteric mechanisms, with high frequency upon mutations. This opened an opportunity to compare the evolutionary capacity of the allosteric and non-allosteric modes of a specific sensory protein. We found that AraC evolved novel sensory function far more rapidly in BIF mode than in allosteric mode. This newly acquired (non-allosteric) sensory function is distinguishable both in its response logic and in sensitivity from original (allosteric) one, and they can be operated simultaneously, independently, and cooperatively, allowing the construction of complex regulatory networks behaviours such as a selective NIMPLY/OR converter and width-tuneable band-pass filter. Together with its high frequency of emergence, BIF can be an overlooked evolutionary driver of the invention of novel biosensors and complex regulatory networks in nature and laboratory.