A functional context for heterogeneity of the circadian clock in cells.

Characterization of circadian systems at the organism level—a top-down approach—has led to definition of unifying properties, a hallmark of the science of chronobiology. The next challenge is to use a bottom-up approach to show how the molecular workings of the cellular circadian clock work as building blocks of those properties. We review new studies, including a recently published PLOS Biology paper by Nikhil and colleagues, that show how programmed but also stochastic generation of variation in cellular circadian period explain important adaptive features of entrained circadian phase. A recent PLOS Biology paper shows that clonal cell populations are themselves a collection heterogeneous cellular circadian clocks; this Primer explores the implications, proposing that the phase of entrainment of biological clocks (to time of day or to season) is granular, built from the contributions of individual cells. [ABSTRACT FROM AUTHOR]