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细胞分裂中受随机分配影响的小型遗传回路动力学

Dynamics of small genetic circuits subject to stochastic partitioning in cell division.

作者信息

Lloyd-Price Jason, Tran Huy, Ribeiro Andre S

机构信息

Laboratory of Biosystem Dynamics, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, PO Box 527, FI-33101 Tampere, Finland.

出版信息

J Theor Biol. 2014 Sep 7;356:11-9. doi: 10.1016/j.jtbi.2014.04.018. Epub 2014 Apr 23.

DOI:10.1016/j.jtbi.2014.04.018
PMID:24768865
Abstract

In prokaryotes, partitioning errors during cell division are expected to be a non-negligible source of cell-to-cell diversity in protein numbers. Here, we make use of stochastic simulations to investigate how different degrees of partitioning errors in division affect the cell-to-cell diversity of the dynamics of two genetic circuits, a bistable switch and a clock. First, we find that on average, the stability of the switch decreases with increasing partitioning errors. Despite this, anti-correlations between sister cells, introduced by the partitioning errors, enhance the chances that one of them will remain in the mother cell's state in the next generation, even if the switch is unstable. This reduces the variance of the proportion of phenotypes across generations. In the genetic clock, we find that the robustness of the period decreases with increasing partitioning errors. Nevertheless, the population synchrony is remarkably robust to most errors, only significantly decreasing for the most extreme degree of errors. We conclude that errors in partitioning affect the dynamics of genetic circuits, but the effects are network-dependent and qualitatively different from noise in gene expression.

摘要

在原核生物中,细胞分裂过程中的分配错误预计是蛋白质数量细胞间差异的一个不可忽视的来源。在此,我们利用随机模拟来研究分裂中不同程度的分配错误如何影响两个遗传回路(一个双稳态开关和一个时钟)动力学的细胞间差异。首先,我们发现平均而言,开关的稳定性会随着分配错误的增加而降低。尽管如此,由分配错误引入的姐妹细胞间的反相关性增加了其中一个在下一代中保持母细胞状态的机会,即使开关不稳定。这降低了各代表型比例的方差。在遗传时钟中,我们发现周期的稳健性会随着分配错误的增加而降低。然而,群体同步对大多数错误具有显著的稳健性,仅在最极端程度的错误情况下才会显著下降。我们得出结论,分配错误会影响遗传回路的动力学,但影响因网络而异,并且在性质上与基因表达中的噪声不同。

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