Quiescence: early evolutionary origins and universality do not imply uniformity

Cell cycle investigations have focused on relentless exponential proliferation of cells, an unsustainable situation in nature. Proliferation of cells, whether microbial or metazoan, is interrupted by periods of quiescence. The vast majority of cells in an adult metazoan lie quiescent. As disruptions in this quiescence are at the foundation of cancer, it will be important for the field to turn its attention to the mechanisms regulating quiescence. While often presented as a single topic, there are multiple forms of quiescence each with complex inputs, some of which are tied to conceptually challenging aspects of metazoan regulation such as size control. In an effort to expose the enormity of the challenge, I describe the differing biological purposes of quiescence, and the coupling of quiescence in metazoans to growth and to the structuring of tissues during development. I emphasize studies in the organism rather than in tissue culture, because these expose the diversity of regulation. While quiescence is likely to be a primitive biological process, it appears that in adapting quiescence to its many distinct biological settings, evolution has diversified it. Consideration of quiescence in different models gives us an overview of this diversity.