Comparing Negative Feedback Mechanisms in Gene Expression: From Single Cells to Cell Populations

Negative feedback regulation is a well-known motif for suppressing deleterious fluctuations in gene product levels. We systematically compare two scenarios where negative feedback is either implemented in the protein production rate (regulated synthesis) or in the protein degradation rate (regulated degradation). Our results show that while in low-noise regimes both schemes are identical, they begin to show remarkable differences in high-noise regimes. Analytically solving for the probability distributions of the protein levels reveals that regulated synthesis is a better strategy to suppress random fluctuations while also minimizing protein levels dipping below a threshold. In contrast, regulated degradation is preferred if the goal is to minimize protein levels going beyond a threshold. Finally, we compare and contrast these distributions not only in a single cell over time but also in an expanding cell population where these effects can be buffered or exacerbated due to the coupling between expression and cell growth.