Synopsis: Biological Oscillations Improve Fidelity

Calculations show that a time-varying molecular input signal can induce a more predictable biological response than a constant input.

The complex molecular networks that underlie biological systems often show time variation, such as oscillations or pulses in the concentrations of various chemicals, but it is not always clear how this variation is useful. Writing in Physical Review Letters, researchers show that, in one biology-inspired model, the response to a time-varying input can reflect the average conditions more reliably than the response to a steady input does.

An important mechanism for regulating cellular activity is the reversible binding of a molecule, called a transcription factor, to a “promoter” region of the DNA, which prods a nearby gene into producing its corresponding protein. Filipe Tostevin and colleagues at the FOM Institute for Atomic and Molecular Physics (AMOLF) in Amsterdam, Netherlands, explored how a mathematical model of this process responds to a time-varying transcription-factor “input.” Such time variation of molecular concentrations often occurs in cells as the result of nonlinear feedback between the activities of various genes.

Even if the concentration of transcription factor is constant, the stochastic nature of the molecular processes, such as transcription-factor binding and unbinding, cause the output of protein to vary with time. The researchers found that this variation can be reduced when the transcription factor appears in repetitive pulses, because a strong pulse virtually guarantees that it will bind to the promoter at a particular time. The improved output variability with pulses occurs for a wide range of the response-time parameters in the model, including values that are similar to those measured in biological systems. – Don Monroe


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