Theoretical models for circadian rhythms in Neurospora and Drosophila.

We examine theoretical models proposed for the molecular mechanism of circadian rhythms in Drosophila. The models are based on the negative feedback exerted by a complex between the PER and TIM proteins on the expression of the per and tim genes. We show that a similar model can account for circadian oscillations in Neurospora, where the protein FRQ negatively regulates the expression of the frq gene. The effect of light on the circadian rhythms is included by considering that it elicits a rise in the rate of TIM degradation in Drosophila, whereas in Neurospora it enhances the rate of frq transcription. The models account for the occurrence of sustained circadian oscillations in continuous darkness in Drosophila and Neurospora. Numerical simulations further indicate that the periodic forcing of circadian oscillations by light-dark cycles can result either in the entrainment to the external periodicity or in aperiodic oscillations (i.e. chaos), depending on the magnitude of the periodic changes in the light-controlled parameter.

[1]  A Goldbeter,et al.  Temperature compensation of circadian rhythms: control of the period in a model for circadian oscillations of the per protein in Drosophila. , 1997, Chronobiology international.

[2]  B. Goodwin.  Oscillatory behavior in enzymatic control processes. , 1965, Advances in enzyme regulation.

[3]  P. Hardin,et al.  per mRNA cycling is locked to lights-off under photoperiodic conditions that support circadian feedback loop function , 1996, Molecular and cellular biology.

[4]  J. Dunlap.  Molecular Bases for Circadian Clocks , 1999, Cell.

[5]  Zuwei Qian,et al.  A light-entrainment mechanism for the Drosophila circadian clock , 1996, Nature.

[6]  Gregor Eichele,et al.  A Differential Response of Two Putative Mammalian Circadian Regulators, mper1 and mper2, to Light , 1997, Cell.

[7]  J. Dunlap,et al.  Nuclear localization is required for function of the essential clock protein FRQ , 1998, The EMBO journal.

[8]  A. Sehgal,et al.  Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by Light , 1996, Cell.

[9]  R J Konopka,et al.  Clock mutants of Drosophila melanogaster. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Rosbash,et al.  Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock , 1995, Neuron.

[11]  Lars Folke Olsen,et al.  Biochemical oscillations and cellular rhythms: The molecular bases of periodic and chaotic behaviour: Albert Goldbeter. Cambridge University Press, Cambridge, 1996. $99.95 (cloth), 605 + xxiv pp , 1997 .

[12]  P. Hardin,et al.  Drosophila Photoreceptors Contain an Autonomous Circadian Oscillator That Can Function without period mRNA Cycling , 1998, The Journal of Neuroscience.

[13]  M. Rosbash,et al.  Temporal phosphorylation of the Drosophila period protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Rosbash.  Molecular control of circadian rhythms. , 1995, Current opinion in genetics & development.

[15]  M. Rosbash,et al.  Post‐transcriptional regulation contributes to Drosophila clock gene mRNA cycling , 1997, The EMBO journal.

[16]  M. W. Young,et al.  Light-Induced Degradation of TIMELESS and Entrainment of the Drosophila Circadian Clock , 1996, Science.

[17]  Jeffrey C. Hall,et al.  A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless , 1998, Cell.

[18]  R. Wever,et al.  Virtual synchronization towards the limits of the range of entrainment. , 1972, Journal of theoretical biology.

[19]  S. Golden,et al.  Circadian clocks in prokaryotes , 1996, Molecular microbiology.

[20]  A. Winfree.  The geometry of biological time , 1991 .

[21]  A. Goldbeter,et al.  Chaos and birhythmicity in a model for circadian oscillations of the PER and TIM proteins in drosophila , 1999, Journal of theoretical biology.

[22]  L. Rensing,et al.  Phase response curves obtained by perturbing different variables of a 24 hr model oscillator based on translational control. , 1982, Journal of theoretical biology.

[23]  Joel D Levine,et al.  Molecular Analysis of Mammalian Timeless , 1998, Neuron.

[24]  A. Goldbeter,et al.  A Model for Circadian Rhythms in Drosophila Incorporating the Formation of a Complex between the PER and TIM Proteins , 1998, Journal of biological rhythms.

[25]  M. Young.  Molecular genetics of biological rhythms , 1993 .

[26]  A. Sehgal,et al.  Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. , 1994, Science.

[27]  Jennifer J. Loros,et al.  Light-induced resetting of a circadian clock is mediated by a rapid increase in frequency transcript , 1995, Cell.

[28]  A. Goldbeter,et al.  Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  Yoshiyuki Sakaki,et al.  Circadian oscillation of a mammalian homologue of the Drosophila period gene , 1997, Nature.

[30]  P Ruoff,et al.  The Goodwin model: simulating the effect of cycloheximide and heat shock on the sporulation rhythm of Neurospora crassa. , 1999, Journal of theoretical biology.

[31]  J. Dunlap,et al.  Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. , 1994, Science.

[32]  Thomas K. Darlington,et al.  Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. , 1998, Science.

[33]  A. Goldbeter.  A model for circadian oscillations in the Drosophila period protein (PER) , 1995, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[34]  A. Goldbeter,et al.  Limit Cycle Models for Circadian Rhythms Based on Transcriptional Regulation in Drosophila and Neurospora , 1999, Journal of biological rhythms.

[35]  J. Dunlap,et al.  Genetics and molecular analysis of circadian rhythms. , 1996, Annual review of genetics.

[36]  R. Kronauer,et al.  Refinement of a limit cycle oscillator model of the effects of light on the human circadian pacemaker. , 1998, Journal of theoretical biology.

[37]  J. Dunlap,et al.  An End in the Beginning , 1998, Science.

[38]  J. C. Hall,et al.  Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Mark J. Zylka,et al.  Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei , 1997, Neuron.

[40]  J. Dunlap,et al.  Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. , 1997, Science.

[41]  Jeffrey C. Hall,et al.  CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless , 1998, Cell.

[42]  J. Thomas,et al.  Genetics in rhythm. , 1997, Trends in genetics : TIG.

[43]  I. Edery,et al.  Resetting the Drosophila Clock by Photic Regulation of PER and a PER-TIM Complex , 1996, Science.

[44]  Yi Liu,et al.  Alternative Initiation of Translation and Time-Specific Phosphorylation Yield Multiple Forms of the Essential Clock Protein FREQUENCY , 1997, Cell.