Cells use genetic switches to shift between alternate gene expression states, e.g., to adapt to new environments or to follow a preprogrammed developmental pathway. Here, we investigate the dynamics of switching between metastable states of a feedback based on/off switch , by employing the WKB theory to treat the underlying master equations. This technique, applicable for any generic feedback function, yields accurate results for the quasi-stationary distributions of mRNA and protein copy numbers and  mean switching time, starting from either state. Our analytical results compare well with Monte Carlo simulations. Importantly, the approach may be used to study the effect of varying biological parameters on the stability of the switch states, and we use it to show that in some cases promoter kinetics, not just thermodynamic stability, can influence switching .
Cells use genetic switches to shift between alternate gene expression states, e.g., to adapt to new environments or to follow a developmental pathway. Here, we study the dynamics of switching in a generic-feedback on/off switch . Unlike protein-only models, we explicitly account for stochastic fluctuations of mRNA, which have a dramatic impact on switch dynamics. Employing the WKB theory to treat the underlying chemical master equations, we obtain accurate results for the quasi-stationary distributions of mRNA and protein copy numbers and for the mean switching time, starting from either state. Our analytical results agree well with Monte Carlo simulations. Importantly, one can use the approach to study the effect of varying biological parameters on switch stability .
D
preprogrammed
R
investigate
study
R
between metastable states of a feedback based
in a generic-feedback
R
, by employing
. Unlike protein-only models, we explicitly account for stochastic fluctuations of mRNA, which have a dramatic impact on switch dynamics. Employing
R
master equations. This technique, applicable for any generic feedback function, yields
chemical master equations, we obtain
A
for the
R
compare
agree
R
the approach may be used
one can use the approach
R
the stability of the switch states, and we use it to show that in some cases promoter kinetics, not just thermodynamic stability, can influence switching
switch stability