Molecular Circadian Oscillators: An Alternative Hypothesis

Results from experiments in different organisms have shown that elements of input pathways can themselves be under circadian control and that outputs might feed back into the oscillator. In addition, it has become clear that there might be redundancies in the generation of circadian rhythmicity, even within single cells. In view of these results, it is worth reevaluating our current working hypotheses about the pacemaker's molecular mechanisms and the involvement of single autoregulatory genes. On one hand, redundancies in the generation of circadian rhythmicity might make the approach of defining a discrete circadian oscillator with the help of single gene mutations extremely difficult. On the other hand, many examples show that components of signal transduction pathways can indeed be encoded by single genes. The authors have constructed a model placing an autoregulatory gene and its products on an input pathway feeding into a separate oscillator. The behavior of this model can explain the majority of results of molecular circadian biology published to date. In addition, it shows that different qualities of the circadian system might be associated with different cellular functions that can exist independently and, only if put together, will lead to the known circadian phenotype.