title: Reduced models of the circadian oscillators in Neurospora crassa and Drosophila melanogaster illustrate mechanistic similarities.
abstract: We have developed a reduced model representing feedback loops of transcriptional regulation underlying circadian rhythms in Neurospora crassa. The model contains two delay differential equations that describe the dynamics of two core gene products, FRQ and WCC. In a negative feedback loop, FRQ protein represses frq transcription by binding the white-collar complex (WCC), which consists of the WC-1 and WC-2 proteins. In a positive feedback loop, WCC indirectly enhances its own formation. The model simulates circadian oscillations, light entrainment, and a phase-response curve (PRC) similar to experimental PRCs. The Neurospora model is virtually identical to a model describing Drosophila circadian rhythm generation, illustrating that rhythm generation in these divergent organisms shares important mechanistic elements. Significant dynamic differences were found when the parameter spaces of both models were explored to analyze changes in oscillations and bifurcations to steady states. Stochastic fluctuations in molecule numbers were simulated with the Gillespie algorithm. Circadian oscillations and entrainment to light were simulated with <80 molecules of FRQ and WCC present on average. Simulations suggest that in both Neurospora and Drosophila, only the negative feedback loop is essential for circadian oscillations. Similar models may aid understanding of circadian mechanisms in mammals and other organisms.
authors.affiliation: Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, Texas 77225, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.forename: John H
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005246:Feedback; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009492:Neurospora crassa / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D014157:Transcription Factors; C105589:wc-1 protein, Neurospora crassa; C103772:white collar 2 protein, Neurospora