A curvature-based criterion for harmonic circadian waveforms

Abstract

Experimental and theoretical studies of circadian rhythms have focused largely on the period, on mutants that alter it and on phase shifts, and this focus has driven the identification of clock genes and clarified how clocks entrain to light--dark cycles. The waveform of the oscillation itself, by contrast, has attracted little attention as an indicator of the properties of the underlying oscillator. To assess the waveform directly, we focus on whether the trajectory in the plane spanned by a variable and its time derivative possesses an inflection point, and we define an oscillation to be harmonic when no inflection point is present. Bioluminescence recordings from cyanobacteria and from the mammalian SCN were harmonic in this sense, as were most of the core clock components in mathematical models of the circadian clock. Numerical analysis of the Goodwin model, a minimal representation of the core circadian oscillator, yielded harmonic oscillation throughout. We confirmed this numerical trend semi-analytically using a piecewise-linearized Goodwin model. Because it evaluates the properties of a waveform without assuming a model structure, the approach we propose offers a new perspective on the waveform analysis of biological rhythms in general, not only circadian ones.