Fluctuation impossibility results for stochastic burst networks

Abstract

Stochastic reaction networks often involve components at low copy number, where individual production and degradation events generate substantial fluctuations. Yan et al.\ conjectured in 2019 that for networks with linear degradation and arbitrary cross-regulatory production rates, feedback cannot suppress the stationary fluctuations for each component below the fluctuations of its constant-rate counterpart. Their formulation allows random burst sizes $K_i$: the unit-birth case has $K_i\equiv1$, the biologically important burst model takes $K_i$ to be geometrically distributed, but more general positive integer-valued burst laws are also permitted. The conjecture was recently proved for unit births, $K_i\equiv1$. We show here that the conjecture is \textit{false in general} by constructing a two-component network with bounded production rates and burst sizes in $\{1,2\}$ for which both stationary Fano factors lie below their common constant-rate baseline. We then prove the conjecture for positive geometric bursts, the canonical burst model in stochastic gene expression. For arbitrary regulatory architecture and nonlinear cross-regulatory production rates, we prove an exact weighted tradeoff that rules out simultaneous suppression of every component below its geometric-burst baseline. We also prove a complementary structural impossibility result for arbitrary positive integer-valued burst laws with finite second moments: if the activating and inhibiting interactions have a globally consistent sign structure, in the sense that every cycle of the regulatory interaction graph contains an even number of negative interactions, then every component individually satisfies $F_{X_i}\ge B_i$, where $F_{X_i}$ is its stationary Fano factor and $B_i$ is its constant-rate burst baseline.