Modeling fruit fly daily rhythms, gene mutations, and light responses using key clock proteins

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.

Simplified