Why biological clocks run on time Mechanism discovered for temperature-independent circadian rhythm

August 15, 2012

Image ©Tomo.Yun

Organisms from bacteria to humans maintain a 24-hour rhythm within their bodies. This circadian rhythm is produced by a circular metabolic process involving a particular protein, but also involves a mystery that has puzzled scientists for decades.

The mystery in question concerns why the reaction that drives the circadian rhythm remains constant despite changes in temperature, even though reactions tend to speed up with increased temperature. Previously it was thought that organisms had some complex mechanism to maintain this rhythm, but the mystery deepened when it was recently shown that it is possible to reproduce such a temperature-independent cycle in a test tube with just three types of proteins.

University of Tokyo Graduate School of Arts and Sciences Professor Kunihiko Kaneko and PhD student Tetsuhiro Hatakeyama have successfully explained the mechanism behind a constant circadian rhythm.

The researchers focused on the amount of enzyme that can be used in the chemical reaction of the circadian rhythm if there is just a single enzyme used across multiple steps in the cycle. As the temperature increases, more and more protein enters a state where it is able to react easily with the enzyme. However, since the amount of enzyme remains constant, competition for it increases and the amount of available enzyme decreases. The researchers used a computer model to demonstrate that the increase in temperature can be offset exactly by the decrease in available enzyme, and the circadian rhythm maintained constant as a result.

Any system using the same enzyme at each step will exhibit the same temperature-independent behavior. Not just limited to circadian rhythms, this discovery may be a key mechanism underlying other processes employed by organisms struggling to maintain biological function and internal conditions in changing environments.

(Public Relations Division: Euan McKay, Azusa Minamizaki)

Department release/press release (Japanese)


Kunihiko Kaneko, Tetsuhiro Hatakeyama
“Generic temperature compensation of biological clocks by autonomous regulation of catalyst concentration”
Proceeding of the National Academy of Sciences of the USA. doi:10.1073/pnas.1120711109
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