A feedback loop that functions via transcription and translation is thought to be the mechanistic core of circadian rhythmicity. Numerous modeling efforts incorporate the identified components and their modifications to recreate the circadian clock in computer simulations. Several issues remain problematic, including the lack of precise quantitative kinetics and the likely existence of additional, as-yet-undiscovered components. Even without these complications, models and flow charts of the circadian system have reached high complexity. They attempt to reconcile all observations without violating current views and concepts. In this article, the authors consider the mechanisms that may have preceded the circadian system in evolution. Given that cellular metabolism and biochemistry were presumably already interconnected in cascading feedback reactions prior to the appendage of the transcription/translation feedback loop, a coordinated response to exogenous changes would be advantageous over unsystematic responses. The authors hypothesize that those mechanisms that allowed synchronization in spite of metabolic complexity form the basis for the evolution of circadian properties and are as fundamental to the circadian system as the transcriptional/translational feedback loop.
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