Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila

Bioessays. 2000 Jan;22(1):84-93. doi: 10.1002/(SICI)1521-1878(200001)22:1<84::AID-BIES13>3.0.CO;2-I.


Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light-induced TIM degradation, the model accounts for damping of oscillations in constant light, entrainment of the rhythm by light-dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84-93, 2000.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Clocks*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Insect Proteins / genetics
  • Insect Proteins / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Period Circadian Proteins


  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • tim protein, Drosophila