Stochasticity in Gene Expression in a Cell-Sized Compartment
Stochasticity in Gene Expression in a Cell-Sized Compartment
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DOI：
10.1021/sb500249g
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发表时间：
2015-05-01
影响因子：
4.7
通讯作者：
Yomo, Tetsuya
中科院分区：
文献类型：
--
作者：
Nishimura, Kazuya;Tsuru, Saburo;Yomo, Tetsuya
克隆细胞群体中的基因表达波动很大，其与各种细胞功能的相关性正在激烈的争论中。一个基本的问题是，这种波动是活细胞的复杂性和冗余性的结果，还是细胞微小的微反应器性质的必然属性。为了回答这个问题，我们构建了一个人工细胞，它只包括基因表达所必需的组件（体外转录和翻译系统）和它的边界作为一个微反应器（细胞大小的脂质囊泡），并研究了基因表达噪音。采用类似于Elowitz及其同事分析大肠杆菌表达噪声的方法，将两种荧光蛋白表达的变化分解为两种蛋白之间相关和不相关的组分。杆菌所观察到的波动进行了比较与理论模型，表示作为中间分子和产品的平均数的函数的噪声的幅度。假设转录本是部分激活的，理论模型能够很好地描述人工系统中的噪声。此外，对E.大肠杆菌细胞中发现，E. coli中表达噪音水平相似。我们的研究结果表明，在细菌细胞中发现的波动水平主要是一种内在属性，即使在细胞的原始形式中也会出现。
The gene expression in a clonal cell population fluctuates significantly, and its relevance to various cellular functions is under intensive debate. A fundamental question is whether the fluctuation is a consequence of the complexity and redundancy in living cells or an inevitable attribute of the minute microreactor nature of cells. To answer this question, we constructed an artificial cell, which consists of only necessary components for the gene expression (in vitro transcription and translation system) and its boundary as a microreactor (cell sized lipid vesicle), and investigated the gene expression noise. The variation in the expression of two fluorescent proteins was decomposed into the components that were correlated and uncorrelated between the two proteins using a method similar to the one used by Elowitz and co-workers to analyze the expression noise in E. coli. The observed fluctuation was compared with a theoretical model that expresses the amplitude of noise as a function of the average number of intermediate molecules and products. With the assumption that the transcripts are partly active, the theoretical model was able to well describe the noise in the artificial system. Furthermore, the same measurement for E. coli cells harboring an identical plasmid revealed that the E. coli exhibited a similar level of expression noise. Our results demonstrated that the level of fluctuation found in bacterial cells is mostly an intrinsic property that arises even in a primitive form of the cell.