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Proceedings of the National Academy of Sciences of the United States of America


The internal circadian rhythms of cells and organisms coordinate their physiological properties to the prevailing 24-h cycle of light and dark on earth. The mechanisms generating circadian rhythms have four defining characteristics: they oscillate endogenously with period close to 24 h, entrain to external signals, suffer phase shifts by aberrant pulses of light or temperature, and compensate for changes in temperature over a range of 10°C or more. Most theoretical descriptions of circadian rhythms propose that the underlying mechanism generates a stable limit cycle oscillation (in constant darkness or dim light), because limit cycles quite naturally possess the first three defining properties of circadian rhythms. On the other hand, the period of a limit cycle oscillator is typically very sensitive to kinetic rate constants, which increase markedly with temperature. Temperature compensation is therefore not a general property of limit cycle oscillations but must be imposed by some delicate balance of temperature dependent effects. However, “delicate balances” are unlikely to be robust to mutations. On the other hand, if circadian rhythms arise from a mechanism that concentrates sensitivity into a few rate constants, then the “balancing act” is likely to be more robust and evolvable. We propose a switch-like mechanism for circadian rhythms that concentrates period sensitivity in just two parameters, by forcing the system to alternate between a stable steady state and a stable limit cycle.