Optimal transition paths of phenotypic switching in a non-Markovian self-regulation gene expression

Gene expression is a complex biochemical process involving multiple reaction steps, creating molecular memory because the probability of waiting time between consecutive reaction steps no longer follows exponential distributions. What effect the molecular memory has on metastable states in gene expression remains not fully understood. Here, we study transition paths of switching between bistable states for a non-Markovian model of gene expression equipped with a self-regulation. Employing the large deviation theory for this model, we analyze the optimal transition paths of switching between bistable states in gene expression, interestingly finding that dynamic behaviors in gene expression along the optimal transition paths significantly depend on the molecular memory. Moreover, we discover that the molecular memory can prolong the time of switching between bistable states in gene expression along the optimal transition paths. Our results imply that the molecular memory may be an unneglectable factor to affect switching between metastable states in gene expression.