Ab initio scaling laws between noise and mean of gene expression

Gene expression is inherently noisy due to fluctuations occurring at the molecular level. From a top-down perspective, noise has been traditionally decomposed into an intrinsic component that scales inversely with the mean expression level and an extrinsic component that is constant in absence of regulatory changes. Here, we adopt a bottom-up approach to reveal that extrinsic noise, by itself, can follow the aforementioned decomposition, which entails that one component of it can be confounded with intrinsic noise. Analytical expressions of the noise-mean relationship were derived for different scenarios, which were in part supported by numerical simulations.