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Biophys J, November 1999, p. 2411-2417, Vol. 77, No. 5

A Simple Model of Circadian Rhythms Based on Dimerization and Proteolysis of PER and TIM

John J. Tyson,* Christian I. Hong,* C. Dennis Thron,# and Bela Novak§

 *Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 USA;  #5 Barrymore Road, Hanover, New Hampshire 03755 USA; and  §Department of Agricultural Chemical Technology, Technical University, Budapest 1521, Hungary

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 24 h. 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 perL mutant phenotype. In addition, the model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch.

Biophys J, November 1999, p. 2411-2417, Vol. 77, No. 5
© 1999 by the Biophysical Society   0006-3495/99/11/2411/07  $2.00


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