Chen Meiling, Luo Songhao, Cao Mengfang, Guo Chengjun, Zhou Tianshou, Zhang Jiajun
Guangdong Province Key Laboratory of Computational Science, Guangzhou 510275, People's Republic of China.
School of Mathematics, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.
Phys Rev E. 2022 Jan;105(1-1):014405. doi: 10.1103/PhysRevE.105.014405.
Gene expression in individual cells is inherently variable and sporadic, leading to cell-to-cell variability in mRNA and protein levels. Recent single-cell and single-molecule experiments indicate that promoter architecture and translational bursting play significant roles in controlling gene expression noise and generating the phenotypic diversity that life exhibits. To quantitatively understand the impact of these factors, it is essential to construct an accurate mathematical description of stochastic gene expression and find the exact analytical results, which is a formidable task. Here, we develop a stochastic model of bursty gene expression, which considers the complex promoter architecture governing the variability in mRNA expression and a general distribution characterizing translational burst. We derive the analytical expression for the corresponding protein steady-state distribution and all moment statistics of protein counts. We show that the total protein noise can be decomposed into three parts: the low-copy noise of protein due to probabilistic individual birth and death events, the noise due to stochastic switching between promoter states, and the noise resulting from translational busting. The theoretical results derived provide quantitative insights into the biochemical mechanisms of stochastic gene expression.
单个细胞中的基因表达本质上是可变且零散的,导致mRNA和蛋白质水平在细胞间存在差异。最近的单细胞和单分子实验表明,启动子结构和翻译爆发在控制基因表达噪声以及产生生命所展现的表型多样性方面发挥着重要作用。为了定量理解这些因素的影响,构建随机基因表达的准确数学描述并找到精确的分析结果至关重要,而这是一项艰巨的任务。在此,我们开发了一个爆发式基因表达的随机模型,该模型考虑了控制mRNA表达变异性的复杂启动子结构以及表征翻译爆发的一般分布。我们推导了相应蛋白质稳态分布和蛋白质计数所有矩统计量的解析表达式。我们表明,总蛋白质噪声可分解为三个部分:由于概率性的个体产生和死亡事件导致的蛋白质低拷贝噪声、由于启动子状态之间的随机切换产生的噪声以及由翻译爆发产生的噪声。所推导的理论结果为随机基因表达的生化机制提供了定量见解。