Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520; email:
Current affiliation: Calico Life Sciences, LLC, South San Francisco, California 94080.
Annu Rev Biophys. 2018 May 20;47:595-616. doi: 10.1146/annurev-biophys-062215-010954. Epub 2018 Apr 4.
Living cells detect and process external signals using signaling pathways that are affected by random fluctuations. These variations cause the behavior of individual cells to fluctuate over time (behavioral variability) and generate phenotypic differences between genetically identical individuals (phenotypic diversity). These two noise sources reduce our ability to predict biological behavior because they diversify cellular responses to identical signals. Here, we review recent experimental and theoretical advances in understanding the mechanistic origin and functional consequences of such variation in Escherichia coli chemotaxis-a well-understood model of signal transduction and behavior. After briefly summarizing the architecture and logic of the chemotaxis system, we discuss determinants of behavior and chemotactic performance of individual cells. Then, we review how cell-to-cell differences in protein abundance map onto differences in individual chemotactic abilities and how phenotypic variability affects the performance of the population. We conclude with open questions to be addressed by future research.
活细胞使用受随机波动影响的信号通路来检测和处理外部信号。这些变化导致单个细胞的行为随时间(行为可变性)发生波动,并在遗传上相同的个体之间产生表型差异(表型多样性)。这两个噪声源降低了我们预测生物行为的能力,因为它们使细胞对相同信号的反应多样化。在这里,我们回顾了理解大肠杆菌趋化作用中这种变化的机制起源和功能后果的最新实验和理论进展——这是信号转导和行为的一个很好理解的模型。在简要总结趋化系统的结构和逻辑之后,我们讨论了单个细胞行为和趋化性能的决定因素。然后,我们回顾了细胞间蛋白质丰度的差异如何映射到个体趋化能力的差异,以及表型可变性如何影响群体的性能。最后,我们提出了未来研究需要解决的开放性问题。