 The study examined how a two-component system composed of a sensor kinase, SK, and a non-partner response regulator, R, could evolve to become more sensitive to external stimuli. It was found that by combining certain mutations in the SK protein, it became capable of phosphorylating the R, which then activated the phosphatase activity of the R towards another target protein, on par. This resulted in a new circuit that was responsive to external signals. By analysing a simplified mathematical model, it was shown that this behaviour could be explained by a single parameter that controlled the strength of the protein-protein interaction. This article was authored by Albert Ciriaporn, Barat Espechuk, Michael T. Lobb, and others.