Peisajovich Sergio G
Department of Cell and Systems Biology, University of Toronto, Toronto, M5S 3G5 Canada.
ACS Synth Biol. 2012 Jun 15;1(6):199-210. doi: 10.1021/sb300012g. Epub 2012 Apr 2.
Signaling networks process vast amounts of environmental information to generate specific cellular responses. As cellular environments change, signaling networks adapt accordingly. Here, I will discuss how the integration of synthetic biology and directed evolution approaches is shedding light on the molecular mechanisms that guide the evolution of signaling networks. In particular, I will review studies that demonstrate how different types of mutations, from the replacement of individual amino acids to the shuffling of modular domains, lead to markedly different evolutionary trajectories and consequently to diverse network rewiring. Moreover, I will argue that intrinsic evolutionary properties of signaling proteins, such as the robustness of wild type functions, the promiscuous nature of evolutionary intermediates, and the modular decoupling between binding and catalysis, play important roles in the evolution of signaling networks. Finally, I will argue that rapid advances in our ability to synthesize DNA will radically alter how we study signaling network evolution at the genome-wide level.
信号网络处理大量的环境信息以产生特定的细胞反应。随着细胞环境的变化，信号网络也会相应地进行适应性调整。在这里，我将讨论合成生物学和定向进化方法的整合如何揭示指导信号网络进化的分子机制。特别是，我将回顾一些研究，这些研究展示了从单个氨基酸的替换到模块化结构域的改组等不同类型的突变如何导致明显不同的进化轨迹，进而导致多样的网络重连。此外，我将论证信号蛋白的内在进化特性，如野生型功能的稳健性、进化中间体的混杂性质以及结合与催化之间的模块化解耦，在信号网络的进化中发挥着重要作用。最后，我将论证我们合成DNA能力的快速进步将从根本上改变我们在全基因组水平上研究信号网络进化的方式。
