Cell Biology

Generating a Biological Oscillator

Science Signaling  08 Jul 2008:
Vol. 1, Issue 27, pp. ec249
DOI: 10.1126/scisignal.127ec249

The components of many of the biochemical circuits that regulate biological functions have been described, and investigators are now able to explore how the components work together and why regulatory networks are connected in a particular way. Tsai et al. note that, although a simple negative feedback loop can create an oscillator, biological oscillators like the pacemaker of the heart or the cell cycle include both negative and positive feedback loops. Modeling of the properties of a range of circuits of these types confirms that the "negative plus positive feedback" option is better for biological applications. This circuit design enables a broad range of control of the frequency without changes in the amplitude of the output of the oscillator, whereas negative feedback alone made an oscillator with a more restricted range of function. Even when the frequency of oscillation does not need to be adjusted, there appear to be advantages to the more complicated circuit; it allows oscillating behavior over a much larger range of enzyme concentrations and kinetic constant values, which may contribute to adaptability during evolution.

T. Y.-C. Tsai, Y. S. Choi, W. Ma, J. R. Pomerening, C. Tang, J. E. Ferrell, Jr., Robust, tunable biological oscillations from interlinked positive and negative feedback loops. Science 321, 126-129 (2008). [Abstract] [Full Text]