The robustness continuum

Organisms are subject to random changes in their external environments, as well as in their internal components. A central goal of evolutionary systems biology is to understand how living systems cope withand in some cases exploitthis variation. Many cellular and developmental processes operate with high fidelity to produce stereotyped, irreversible outcomes despite environmental and genetic perturbation. These processes are said to be robust or insensitive to variation. Robustness can lead to single, invariant phenotypes, or it can take the form of phenotypic plasticity, in which different environmental conditions reproducibly induce distinct phenotypes. Some organisms cope with environmental variation not with robust responses but with stochastic, reversible fate decisions. In those organisms, lower robustness yields heterogeneity among individuals, which in turn serves as a bet-hedging mechanism for the population. Considering high-fidelity and bet-hedging processes togetheras a robustness continuumprovides a unifying framework for analyzing and conceptualizing variation in complex evolving systems. This framework can be applied to understanding the architectures and dynamics of the regulatory networks that underlie fate decisions in microbes, plants, animals, and cancer cells.