Non-sinusoidal Waveform in Temperature-Compensated Circadian Oscillations.

Time series of biological rhythms are of various shapes. Here, we investigated the waveforms of circadian rhythms in gene-protein dynamics using a newly developed, to our knowledge, index to quantify the degree of distortion from a sinusoidal waveform. In general, most biochemical reactions accelerate with increasing temperature, but the period of circadian rhythms remains relatively stable with temperature change, a phenomenon known as "temperature compensation." Despite extensive research, the mechanism underlying this remains unclear. To understand the mechanism, we used transcriptional-translational oscillator models for circadian rhythms in the fruit fly Drosophila and mammals. Given the assumption that reaction rates increase with temperature, mathematical analyses revealed that temperature compensation required waveforms that are more nonsinusoidal at higher temperatures. We then analyzed a post-translational oscillator (PTO) model of cyanobacteria circadian rhythms. Because the structure of the PTO is different from that of the transcriptional-translational oscillator, the condition for temperature compensation would be expected to differ. Unexpectedly, the computational analysis again showed that temperature compensation in the PTO model required a more nonsinusoidal waveform at higher temperatures. This finding held for both models even with a milder assumption that some reaction rates do not change with temperature, which is consistent with experimental evidence. Together, our theoretical analyses predict that the waveform of circadian gene-activity and/or protein phosphorylation rhythms would be more nonsinusoidal at higher temperatures, even when there are differences in the network structures.