Transmission and filtering of stochastic rhythms in bursty gene expression

Abstract

How stochastic rhythms in upstream regulatory signals are transmitted to downstream gene expression is a fundamental question in systems biology. Although experiments have shown that molecular degradation strongly influences downstream rhythmic responses, a general quantitative theory explaining how degradation, stochastic bursting, and upstream timing variability jointly govern rhythm transmission remains lacking. Here we develop a general analytical framework based on a martingale-based orthogonal decomposition, applicable to arbitrarily complex upstream dynamics, including memory effects. We derive exact autocorrelation and power-spectrum transmission laws, establish an oscillation-efficiency contraction principle, and identify a critical degradation rate that provides a necessary and sufficient condition for stochastic rhythm transmission. An explicit rhythm-transmission relation reveals that increasing burst frequency and modulation depth promotes rhythm transmission, whereas greater variability in upstream cycle duration suppresses it. In particular, increasing burst size leaves oscillation efficiency unchanged. The predicted degradation threshold correctly separates all ten pulsing and nonpulsing p53 target proteins reported in previous experiments. These results provide a theoretical foundation for understanding how cells selectively preserve or integrate rhythmic regulatory signals.