Robust oscillations within the interlocked feedback model of Drosophila circadian rhythm

J Theor Biol. 2001 Jun 21;210(4):401-6. doi: 10.1006/jtbi.2000.2226.


A mechanism for generating circadian rhythms has been of major interest in recent years. After the discovery of per and tim, a model with a simple feedback loop involving per and tim has been proposed. However, it is recognized that the simple feedback model cannot account for phenotypes generated by various mutants. A recent report by Glossop, Lyons & Hardin [Science286, 766 (1999)] on Drosophila suggests involvement of another feedback loop by dClk that is interlocked with per-tim feedback loop. In order to examine whether interlocked feedback loops can be a basic mechanism for circadian rhythms, a mathematical model was created and examined. Through extensive simulation and mathematical analysis, it was revealed that the interlocked feedback model accounts for the observations that are not explained by the simple feedback model. Moreover, the interlocked feedback model has robust properties in oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CLOCK Proteins
  • Circadian Rhythm*
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Feedback
  • Gene Expression
  • Genes, Insect*
  • Insect Proteins / genetics
  • Models, Biological
  • Nuclear Proteins / genetics
  • Period Circadian Proteins
  • Transcription Factors / genetics


  • Clk protein, Drosophila
  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Transcription Factors
  • tim protein, Drosophila
  • CLOCK Proteins