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Protein hourglass: Exact first passage time distributions for protein thresholds
Physical Review E ( IF 2.2 ) Pub Date : 2020-11-30 , DOI: 10.1103/physreve.102.052413
Krishna Rijal 1 , Ashok Prasad 2 , Dibyendu Das 1
Affiliation  

Protein thresholds have been shown to act as an ancient timekeeping device, such as in the time to lysis of Escherichia coli infected with bacteriophage λ . The time taken for protein levels to reach a particular threshold for the first time is defined as the first passage time (FPT) of the protein synthesis system, which is a stochastic quantity. The first few moments of the distribution of first passage times were known earlier, but an analytical expression for the full distribution was not available. In this work, we derive an analytical expression for the first passage times for a long-lived protein. This expression allows us to calculate the full distribution not only for cases of no self-regulation, but also for both positive and negative self-regulation of the threshold protein. We show that the shape of the distribution matches previous experimental data on λ-phage lysis time distributions. We also provide analytical expressions for the FPT distribution with non-zero degradation in Laplace space. Furthermore, we study the noise in the precision of the first passage times described by coefficient of variation (CV) of the distribution as a function of the protein threshold value. We show that under conditions of positive self-regulation, the CV declines monotonically with increasing protein threshold, while under conditions of linear negative self-regulation, there is an optimal protein threshold that minimizes the noise in the first passage times.

中文翻译:


蛋白质沙漏:蛋白质阈值的精确首次通过时间分布



蛋白质阈值已被证明可以作为一种古老的计时装置,例如在裂解感染噬菌体的大肠杆菌的时间中 λ 。蛋白质水平首次达到特定阈值所需的时间定义为蛋白质合成系统的首次传代时间(FPT),它是一个随机量。首次通过时间分布的前几个矩较早已知,但无法获得完整分布的解析表达式。在这项工作中,我们推导出长寿命蛋白质首次传代时间的分析表达式。该表达式使我们不仅可以计算无自我调节情况的完整分布,还可以计算阈值蛋白的正向和负向自我调节的完整分布。我们证明分布的形状与之前的实验数据相匹配 λ -噬菌体裂解时间分布。我们还提供了拉普拉斯空间中具有非零退化的 FPT 分布的解析表达式。此外,我们研究了由分布的变异系数(CV)描述的首次传代时间精度中的噪声作为蛋白质阈值的函数。我们发现,在正向自我调节的条件下,CV随着蛋白质阈值的增加而单调下降,而在线性负向自我调节的条件下,存在一个最佳的蛋白质阈值,可以最大限度地减少第一次传代中的噪音。
更新日期:2020-12-01
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