Beyond homeostasis: a predictive-dynamic framework for understanding cellular behavior.

Microbial regulatory strategies have long been understood in terms of the homeostatic framework, in which a response is interpreted as a restoring force counteracting the immediate intracellular consequences of a change in the environment. In this review, we summarize the breadth of recent discoveries of cellular behavior extending beyond the homeostatic framework. We argue that the nonrandom structure of native habitats makes environmental fluctuations inherently multidimensional. Beyond its utility for accurate perception of immediate events, the temporal regularity of this multidimensional correlation structure allows microbes to make predictions about the trajectory of their sensory environment. We describe recently discovered examples of such predictive behavior, their physiological benefits, and the underlying evolutionary forces shaping them. These observations compel us to go beyond homeostasis and consider a predictive-dynamic framework in which cellular behavior is orchestrated in response to the meaning of an environmental perturbation, not only its direct and immediate fitness consequences.