Abstract
Circadian rhythms, characterized by a period of about 24h, are generated
in nearly all living organisms by the negative autoregulation of
clock gene expression. Deterministic models based on this genetic
regulation account for circadian oscillations in constant environmental
conditions (e.g., in constant darkness) and for entrainment of these
rhythms by light-dark cycles. When the number of clock mRNA and protein
molecules is low, it is necessary to resort to stochastic simulations
to assess the influence of molecular noise on circadian oscillations.
Indeed, it is possible that the autoregulatory mechanism of gene
expression might not produce stable rhythms due to fluctuations if
the number of molecules involved in the clock mechanism remains too
low. We have compared the deterministic and stochastic approaches
for a model based on the negative autoregulation of a clock gene.
We show by means of stochastic simulations that robust circadian
oscillations can already occur when the maximum number of mRNA and
protein molecules is of the order of a few tens or hundreds, respectively.
Furthermore, the results indicate that the cooperativity characterizing
the repression of the transcription process strenghtens the robustness
of circadian rhythms and that entrainment by light-dark cycles stabilizes
the phase of the oscillations.
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