Maintaining gene expression levels by positive feedback in burst size in the presence of infinitesimal delay

Abstract

Synthesis of individual molecules in the expression of genes often occurs in bursts of multiple copies. Gene regulatory feedback can affect the frequency with which these bursts occur or their size. Whereas frequency regulation has traditionally received more attention, we focus specifically on the regulation of burst size. It turns out that there are (at least) two alternative formulations of feedback in burst size. In the first, newly produced molecules immediately partake in feedback, even within the same burst. In the second, there is no within-burst regulation due to what we call infinitesimal delay. We describe both alternatives using a minimalistic Markovian drift-jump framework combining discrete and continuous dynamics. We derive detailed analytic results and efficient simulation algorithms for positive noncooperative autoregulation (whether infinitesimally delayed or not). We show that at steady state both alternatives lead to a gamma distribution of protein level. The steady-state distribution becomes available only after a transcritical bifurcation point is passed. Interestingly, the onset of the bifurcation is postponed by the inclusion of infinitesimal delay.