Periodically oscillating biochemical systems are like internal clocks for organisms. The stochastic nature of their underlying dynamics — from proteins cycling through different states, for example — inevitably generates random fluctuations in the oscillation periods. As these oscillations can hamper biological function, it has been conjectured that real oscillators are optimized to suppress them. But Robert Marsland III and co-workers have now shown that real biochemical clocks operate in a regime that is far from optimal.
Thermodynamic uncertainty relations impose a trade-off between the fluctuations and dissipation of a non-equilibrium current or, in this case, in the first-passage time required to accumulate a fixed current. Through these relations, the authors determined an upper bound to the accuracy of a clock in relation to its entropy production per cycle. Computational models of real biochemical clocks, such as the KaiC protein, were found to perform well below this optimum. The shortfall may be due to the additional complexity required by optimality and existing biological constraints.