Lei Xue, Tian Wei, Zhu Hongyuan, Chen Tianqi, Ao Ping
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
Sci Rep. 2015 Sep 2;5:13597. doi: 10.1038/srep13597.
Genetically identical cells exposed to homogeneous environment can show remarkable phenotypic difference. To predict how phenotype is shaped, understanding of how each factor contributes is required. During gene expression processes, noise could arise either intrinsically in biochemical processes of gene expression or extrinsically from other cellular processes such as cell growth. In this work, important noise sources in gene expression of phage λ lysogen are quantified using models described by stochastic differential equations (SDEs). Results show that DNA looping has sophisticated impacts on gene expression noise: When DNA looping provides autorepression, like in wild type, it reduces noise in the system; When the autorepression is defected as it is in certain mutants, DNA looping increases expression noise. We also study how each gene operator affects the expression noise by changing the binding affinity between the gene and the transcription factor systematically. We find that the system shows extraordinarily large noise when the binding affinity is in certain range, which changes the system from monostable to bistable. In addition, we find that cell growth causes non-negligible noise, which increases with gene expression level. Quantification of noise and identification of new noise sources will provide deeper understanding on how stochasticity impacts phenotype.
暴露于同质环境中的基因相同的细胞可能表现出显著的表型差异。为了预测表型是如何形成的，需要了解每个因素是如何起作用的。在基因表达过程中，噪声可能内在地产生于基因表达的生化过程中，或者外在地来自其他细胞过程，如细胞生长。在这项工作中，使用随机微分方程（SDEs）描述的模型对噬菌体λ溶原菌基因表达中的重要噪声源进行了量化。结果表明，DNA环化对基因表达噪声有复杂的影响：当DNA环化提供自抑制时，如在野生型中，它会降低系统中的噪声；当自抑制像在某些突变体中那样出现缺陷时，DNA环化会增加表达噪声。我们还通过系统地改变基因与转录因子之间的结合亲和力，研究了每个基因操纵子如何影响表达噪声。我们发现，当结合亲和力处于一定范围内时，系统会表现出异常大的噪声，这会使系统从单稳态转变为双稳态。此外，我们发现细胞生长会导致不可忽视的噪声，这种噪声会随着基因表达水平的增加而增加。噪声的量化和新噪声源的识别将为随机过程如何影响表型提供更深入的理解。
