Stochastic mechanisms in gene expression
Stochastic mechanisms in gene expression
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DOI：
10.1073/pnas.94.3.814
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发表时间：
1997-02-04
影响因子：
11.1
通讯作者：
Arkin, A
中科院分区：
文献类型：
--
作者：
McAdams, HH;Arkin, A
在细胞调控网络中，基因活性由分子信号控制，这些分子信号决定给定基因转录的时间和频率。在基因控制的通路中，一个基因编码的蛋白质产物常常调控其他基因的表达。在第一个启动子被激活后，达到能控制下一个启动子的有效水平所需的时间延迟取决于蛋白质积累的速率。我们分析了在单个这样的“基因耦合”连接中控制转录起始和翻译终止的化学反应，以此作为对由许多此类连接构建的网络进行建模的前期准备。对基因表达过程的模拟表明，蛋白质从一个被激活的启动子以随机时间间隔、数量可变的短脉冲形式产生。因此，在整个细胞群体中，调控级联中连续事件之间的时间可能存在很大差异。此外，竞争性效应物的随机表达模式可在选择不同调控路径的转换机制中产生概率性结果。其结果可能是随着细胞遵循不同路径，细胞群体分化为不同表型。原核细胞和真核细胞的同基因群体中存在许多无法解释的表型变异的例子，这些可能是这些随机基因表达机制的结果。
In cellular regulatory networks, genetic activity is controlled by molecular signals that determine when and how often a given gene is transcribed. In genetically controlled pathways, the protein product encoded by one gene often regulates expression of other genes. The time delay, after activation of the first promoter, to reach an effective level to control the next promoter depends on the rate of protein accumulation. We have analyzed the chemical reactions controlling transcript initiation and translation termination in a single such ''genetically coupled'' link as a precursor to modeling networks constructed from many such links. Simulation of the processes of gene expression shows that proteins are produced from an activated promoter in short bursts of variable numbers of proteins that occur at random time intervals. As a result, there can be large differences in the time between successive events in regulatory cascades across a cell population. In addition, the random pattern of expression of competitive effecters can produce probabilistic outcomes in switching mechanisms that select between alternative regulatory paths. The result can be a partitioning of the cell population into different phenotypes as the cells follow different paths. There are numerous unexplained examples of phenotypic variations in isogenic populations of both prokaryotic and eukaryotic cells that may be the result of these stochastic gene expression mechanisms.