Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

Type

Journal article

Journal

Biophys J

Publication Date

1999

Volume

77

Pages

2411 - 2417

Keywords

Animals *Circadian Rhythm/genetics Drosophila Proteins/*chemistry/genetics/*metabolism Drosophila melanogaster/genetics/metabolism Feedback, Physiological *Models, Biological Mutation Period Circadian Proteins/*chemistry/genetics/*metabolism Phosphorylation *Protein Multimerization Protein Structure, Quaternary