Nishimura Kazuya, Tsuru Saburo, Suzuki Hiroaki, Yomo Tetsuya
†Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Yamadaoka 1-5, Suita, Osaka 565-0871, Japan.
‡Quantitative Biology Center (QBiC), Riken, Fuedai 6-2-3, Suita, Osaka 565-0874, Japan.
ACS Synth Biol. 2015 May 15;4(5):566-76. doi: 10.1021/sb500249g. Epub 2014 Oct 27.
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.
克隆细胞群体中的基因表达会显著波动，其与各种细胞功能的相关性正处于激烈争论中。一个基本问题是，这种波动是活细胞中复杂性和冗余性的结果，还是细胞微小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，它仅由基因表达所需的组件（体外转录和翻译系统）及其作为微反应器的边界（细胞大小的脂质囊泡）组成，并研究了基因表达噪声。使用类似于埃洛维茨及其同事用于分析大肠杆菌中表达噪声的方法，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成分。将观察到的波动与一个理论模型进行比较，该模型将噪声幅度表示为中间分子和产物平均数量的函数。在转录本部分活跃的假设下，该理论模型能够很好地描述人工系统中的噪声。此外，对携带相同质粒的大肠杆菌细胞进行的相同测量表明，大肠杆菌表现出相似水平的表达噪声。我们的结果表明，细菌细胞中发现的波动水平大多是一种内在属性，即使在原始形式的细胞中也会出现。
