School of Mathematics and Statistics, Xuzhou University of Technology, Xuzhou 221111, People's Republic of China.
School of Science, Nanchang University, Nanchang 330031, People's Republic of China.
Phys Rev E. 2021 Feb;103(2-1):022409. doi: 10.1103/PhysRevE.103.022409.
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.
基因表达是一个复杂的生化过程，涉及多个反应步骤，由于连续反应步骤之间的等待时间概率不再遵循指数分布，因此产生了分子记忆。分子记忆对基因表达中亚稳态的影响尚不完全清楚。在这里，我们研究了带有自我调节的非马尔可夫基因表达模型中双稳态之间切换的转移路径。对于这个模型，我们采用大偏差理论，分析了基因表达中双稳态之间切换的最优转移路径，有趣的是，我们发现基因表达沿最优转移路径的动态行为显著依赖于分子记忆。此外，我们发现分子记忆可以延长基因表达沿最优转移路径在双稳态之间切换的时间。我们的结果表明，分子记忆可能是影响基因表达中亚稳态之间切换的一个不可忽视的因素。
