Centre for Synthetic Biology and Innovation, Imperial College London, London, UK.
Adv Exp Med Biol. 2012;751:411-29. doi: 10.1007/978-1-4614-3567-9_19.
Evolution undoubtedly shapes the architecture of biological systems, yet it is unclear which features of regulatory, metabolic, and signalling circuits have adaptive significance and how the architecture of these circuits constrains or promotes evolutionary processes, such as adaptation to new environments. Experimentally rewiring circuits using genetic engineering and constructing novel circuits in living cells allows direct testing and validation of hypotheses in evolutionary systems biology. Building synthetic genetic systems enables researchers to explore regions of the genotype-phenotype and fitness landscapes that may be inaccessible to more traditional analysis. Here, we review the strategies that allow synthetic systems to be constructed and how evolutionary design principles have advanced these technologies. We also describe how building small genetic regulatory systems can provide insight on the trade-offs that constrain adaptation and can shape the structure of biological networks. In the future, the possibility of building biology de novo at the genome scale means that increasingly sophisticated models of the evolutionary dynamics of networks can be proposed and validated, and will allow us to recreate ancestral systems in the lab. This interplay between evolutionary systems theory and engineering design may illuminate the fundamental limits of performance, robustness, and evolvability of living systems.
进化无疑塑造了生物系统的结构，但尚不清楚调控、代谢和信号电路的哪些特征具有适应性意义，以及这些电路的结构如何限制或促进进化过程，例如适应新环境。使用遗传工程对电路进行实验性重布线，并在活细胞中构建新的电路，可以直接测试和验证进化系统生物学中的假设。构建合成遗传系统使研究人员能够探索基因型-表型和适应度景观的区域，这些区域可能无法通过更传统的分析来访问。在这里，我们回顾了允许构建合成系统的策略，以及进化设计原则如何推进这些技术。我们还描述了构建小型遗传调控系统如何提供有关限制适应的权衡的见解，并可以塑造生物网络的结构。在未来，以基因组规模从头构建生物学的可能性意味着可以提出和验证越来越复杂的网络进化动力学模型，并允许我们在实验室中重现祖先系统。进化系统理论和工程设计之间的这种相互作用可能会阐明生命系统性能、鲁棒性和可进化性的基本限制。
