A MODEL FOR CIRCADIAN OSCILLATIONS IN THE DROSOPHILA PERIOD PROTEIN (PER)

The mechanism of circadian oscillations in the period protein (PER) in Drosophila is investigated by means of a theoretical model. Taking in to account recent experimental observations, the model for the circadi an clock is based on multiple phosphorylation of PER and on the negati ve feedback exerted by PER on the transcription of the period (per) ge ne. This minimal biochemical model provides a molecular basis for circ adian oscillations of the limit cycle type. During oscillations, the p eak in per mRNA precedes by several hours the peak in total PER protei n. The results support the view that multiple PER phosphorylation intr oduces times delays which strengthen the capability of negative feedba ck to produce oscillations. The analysis shows that the rhythm only oc curs in a range bounded by two critical values of the maximum rate of PER degradation. A similar result is obtained with respect to the rate of PER transport into the nucleus. The results suggest a tentative ex planation for the altered period of per mutants, in terms of variation s in the rate of PER degradation.