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Simulation of Drosophila Circadian Oscillations, Mutations, and Light Responses by a Model with VRI, PDP-1, and CLK
Modeling fruit fly daily rhythms, gene mutations, and light responses using key clock proteins
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Abstract
A model of Drosophila circadian rhythm generation was developed to represent feedback loops based on transcriptional regulation.
- Histone acetylation kinetics may make transcriptional activation a nonlinear function of CLK levels.
- Oscillations of the protein PER were preserved even when Clk, vri, or Pdp-1 expression was fixed, suggesting that positive feedback loops involving Clk are not essential for oscillations.
- Fixing vri expression altered the oscillation period, indicating its role in regulating circadian rhythms.
- Eliminating the negative feedback loop where PER represses per expression abolished oscillations entirely.
- Simulations mimicked experimental results for per or Clk null mutations, per overexpression, and heterozygous null mutations of vri, Clk, or Pdp-1.
- The model predicts a photic phase-response curve similar to experimental data and simulates oscillations entrained to light-dark cycles.
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