Systems Bioinformatics, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU Amsterdam, De Boelelaan 1087, NL1081, HV, Amsterdam, The Netherlands.
Molecular Cell Physiology, AIMMS, VU Amsterdam, De Boelelaan 1087, NL1081, HV, Amsterdam, The Netherlands.
Sci Rep. 2017 Jul 24;7(1):6299. doi: 10.1038/s41598-017-05871-3.
Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular growth rate influences mean protein expression, little is known about the relationship between growth rate and noise in protein expression. Here we quantify this relationship in Bacillus subtilis by a novel combination of experiments and theory. We measure the effects of promoter activity and growth rate on the expression of a fluorescent protein in single cells. We disentangle the observed protein expression noise into protein-specific and systemic contributions, using theory and variance decomposition. We find that noise in protein expression depends solely on mean expression levels, regardless of whether expression is set by promoter activity or growth rate, and that noise increases linearly with growth rate. Our results can aid studies of (synthetic) gene circuits of single cells and their condition dependence.
蛋白质在单细胞中的表达取决于其整体生理状态。此外,由于生化过程、细胞生长和分裂的随机性,遗传上相同的细胞在蛋白质表达中表现出可变性(噪声)。虽然人们已经很好地理解了细胞生长速率如何影响平均蛋白质表达,但对于生长速率与蛋白质表达噪声之间的关系知之甚少。在这里,我们通过实验和理论的新组合来定量研究枯草芽孢杆菌中的这种关系。我们测量了启动子活性和生长速率对单个细胞中荧光蛋白表达的影响。我们使用理论和方差分解将观察到的蛋白质表达噪声分解为蛋白质特异性和系统贡献。我们发现,蛋白质表达噪声仅取决于平均表达水平,而与表达是由启动子活性还是生长速率决定无关,并且噪声随生长速率线性增加。我们的结果可以帮助研究单细胞的(合成)基因回路及其条件依赖性。