MOLECULAR CIRCADIAN OSCILLATORS - AN ALTERNATIVE HYPOTHESIS

Results from experiments in different organisms have shown that elemen ts of input pathways can themselves be under circadian control and tha t outputs might feed back into the oscillator. in addition, it has bec ome clear that there might be redundancies in the generation of circad ian rhythmicity, even within single cells. In view of these results, i t is worth reevaluating our current working hypotheses about the pacem aker's molecular mechanisms and the involvement of single autoregulato ry genes. On one hand, redundancies in the generation of circadian rhy thmicity might make the approach of defining a discrete circadian osci llator with the help of single gene mutations extremely difficult. On the other hand, many examples show that components of signal transduct ion pathways can indeed be encoded by single genes. The authors have c onstructed a model placing an autoregulatory gene and its products on an input pathway feeding into a separate oscillator. The behavior of t his model can explain the majority of results of molecular circadian b iology published to date. In addition, it shows that different qualiti es of the circadian system might be associated with different cellular functions that can exist independently and, only if put together, wil l lead to the known circadian phenotype.