The Goodwin oscillator: On the importance of degradation reactions in the circadian clock

This article focuses on the Goodwin oscillator and related minimal models, which describe negative feedback schemes that are of relevance for the circ adian rhythms in Neurospora, Drosophila, and probably also in mammals. The temperature behavior of clock mutants in Neurospora crassa and Drosophila m elanogaster are well described by the Goodwin model, at least on a semi-qua ntitative level. A similar semi-quantitative description has been found for Neurospora crassa phase response curves with respect to moderate temperatu re pulses, heat shock pulses, and pulses of cycloheximide. A characteristic feature in the Goodwin and related models is that degradation of clock-mRN A and clock protein species plays an important role in the control of the o scillator's period. As predicted by this feature, recent experimental resul ts from Neurospora crassa indicate that the clock (FRQ) protein of the long period mutant frq(7) is degraded approximately twice as slow as the corres ponding wild-type protein. Quantitative RT-PCR indicates that experimental frq(7)-mRNA concentrations are significantly higher than wild-type levels. The latter findings cannot be modeled by the Goodwin oscillator Therefore, a threshold inhibition mechanism of transcription is proposed.