From fluctuations to phenotypes: the physiology of noise.
There are fundamental physical reasons why biochemical processes might be subject to noise and stochastic fluctuations. Indeed, it has long been understood that random molecular-scale mechanisms, such as those that drive genetic mutation, lie at the heart of population-scale evolutionary dynamics. What we can now appreciate is how stochastic fluctuations inherent in biochemical processes contribute to cellular and organismal phenotypes. Advancements in techniques for empirically measuring single cells and in corresponding theoretical methods have enabled the rigorous design and interpretation of experiments that provide incontrovertible proof that there are important endogenous sources of stochasticity that drive biological processes at the scale of individual organisms. Recently, some studies have progressed beyond merely ascertaining the presence of noise in biological systems; they trace its role in cellular physiology as it is passed through and processed by the biomolecular pathways-from the underlying origins of stochastic fluctuations in random biomolecular interactions to their ultimate manifestations in characteristic species phenotypes. These emerging results suggest new biological network design principles that account for a constructive role played by noise in defining the structure, function, and fitness of biological systems. They further show that stochastic mechanisms open novel classes of regulatory, signaling, and organizational choices that can serve as efficient and effective biological solutions to problems that are more complex, less robust, or otherwise suboptimal to deal with in the context of purely deterministic systems. Research in Drosophila melanogaster eye color-vision development and Bacillus subtilis competence induction has elegantly traced the role of noise in vital physiological processes from fluctuations to phenotypes, and is used here to highlight these developments.