A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM

Many organisms display rhythms of physiology and behavior that are entraine d to the 24-h cycle of light and darkness prevailing on Earth. Under consta nt conditions of illumination and temperature, these internal biological rh ythms persist with a period close to 1 day("circadian"), but it is usually not exactly 24 h. Recent discoveries have uncovered stunning similarities a mong the molecular circuitries of circadian clocks in mice, fruit flies, an d bread molds. A consensus picture is coming into focus around two proteins (called PER and TIM in fruit flies), which dimerize and then inhibit trans cription of their own genes. Although this picture seems to confirm a vener able model of circadian rhythms based on time-delayed negative feedback, we suggest that just as crucial to the circadian oscillator is a positive fee dback loop based on stabilization of PER upon dimerization. These ideas can be expressed in simple mathematical form(phase plane portraits), and the m odel accounts naturally for several hallmarks of circadian rhythms, includi ng temperature compensation and the per(L) mutant phenotype. In addition, t he model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch.