Analytic solutions for the circadian oscillator characterize cycle dynamics and its robustness.

Abstract

Circadian clocks form a fundamental mechanism that promotes the correct behavior of many cellular and molecular processes by synchronizing them on a 24 h period. However, the circadian cycles remain difficult to describe mathematically. To overcome this problem, we first propose a segmentation of the circadian cycle into eight stages based on the levels of expression of the core clock components CLOCK:BMAL1, REV-ERB and PER:CRY. This cycle segmentation is next characterized through a piecewise affine model, whose analytical study allows us to propose an Algorithm to generate biologically-consistent circadian oscillators. Our study provides a characterization of the cycle dynamics in terms of four fundamental threshold parameters and one scaling parameter, shows robustness of the circadian system and its period, and identifies critical points for correct cycle progression.