Evolving the best body clock

Circadian rhythms are metabolic processes that vary and repeat on a 24-hour cycle. They have evolved in many organisms as a survival strategy to synchronize activities with the time of day. Yet many details about how these rhythms work and have evolved remain unknown. Yoshihiko Hasegawa from the University of Tokyo and Masanori Arita from the RIKEN Center for Sustainable Resource Science have now developed a generalized mathematical model that explores the principles by which circadian rhythms are controlled¹.

Mechanisms governing circadian rhythms need to sustain two seemingly conflicting behaviors: they must achieve sufficient regularity and autonomy to allow them to keep time precisely, and yet must also be flexible enough to allow them to be changed or ‘entrained’ in response to external inputs. A human traveling from Japan to Europe, for example, has an internal ‘body clock’ that knows the approximate time of day without seeing sunlight, yet we know through experience that the clock can adjust reasonably quickly to the different time zone.

One of the key issues that the model addresses is how this trade-off between regularity and entrainability can be optimized. The mathematical model generalizes such variables as the actual concentrations of chemicals, the rates of their synthesis and degradation, and the level of random ‘noise’, and instead focuses on how sunlight and light pulses affect the internal clock, a notion referred to as ‘phase response’.

The researchers found that conditions that optimized entrainability and regularity replicated key features of real circadian rhythms that have been studied in mice and hamsters. “For example,” Arita explains, “the model revealed that the optimal clock response includes a dead zone—a time found in real circadian rhythms during which light pulses will neither advance nor delay the biological clock.” The researchers believe that in addition to addressing how the rhythms work, the model may also suggest how they may have evolved.

Arita hopes that other researchers may be able to test the applicability of the model to humans. He suggests it may also be relevant to cave-dwelling or deep-sea animals, which may only have relics of a body clock since they live in the dark. The work could also help in the search for key biological components responsible for circadian rhythms. “It should be useful for distinguishing molecules most likely to be involved from the wider range of candidate molecules that other researchers are identifying,” says Arita.