(Re)inventing the Circadian Feedback Loop

For 20 years, researchers have thought that circadian clocks are defined by feedback loops of transcription and translation. The rediscovery of posttranslational circadian oscillators in diverse organisms forces us to rethink this paradigm. Meanwhile, the original “basic” feedback loops of canonical circadian clocks have swelled to include dozens of additional proteins acting in interlocked loops. We review several self-sustained clock mechanisms and propose that minimum requirements for diurnal timekeeping might be simpler than those of actual free-running circadian oscillators. Thus, complex mechanisms of circadian timekeeping might have evolved from random connections between unrelated feedback loops with independent but limited time-telling capability.