Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Syst. 2017 Feb 22;4(2):171-181.e8. doi: 10.1016/j.cels.2016.12.009. Epub 2017 Jan 11.
Evolution repeatedly converges on only a few regulatory circuit designs that achieve a given function. This simplicity helps us understand biological networks. However, why so few circuits are rediscovered by evolution is unclear. We address this question for the case of fold-change detection (FCD): a response to relative changes of input rather than absolute changes. Two types of FCD circuits recur in biological systems-the incoherent feedforward and non-linear integral-feedback loops. We performed an analytical screen of all three-node circuits in a class comprising ∼500,000 topologies. We find that FCD is rare, but still there are hundreds of FCD topologies. The two experimentally observed circuits are among the very few minimal circuits that optimally trade off speed, noise resistance, and response amplitude. This suggests a way to understand why evolution converges on only few topologies for a given function and provides FCD designs for synthetic construction and future discovery.
进化反复集中在仅少数几个能够实现给定功能的调控回路设计上。这种简单性有助于我们理解生物网络。然而，进化为什么很少重新发现这些回路尚不清楚。我们针对折叠变化检测（FCD）的情况来解决这个问题：一种对输入相对变化而不是绝对变化的响应。两种类型的 FCD 回路在生物系统中反复出现——非相干前馈和非线性积分反馈环。我们对包含约 50 万个拓扑结构的一类中的所有三节点回路进行了分析筛选。我们发现 FCD 很少见，但仍然有数百种 FCD 拓扑结构。这两种实验观察到的回路是少数最优权衡速度、噪声抗性和响应幅度的最小回路之一。这为理解为什么进化只为给定功能收敛到少数拓扑结构提供了一种方法，并为合成构建和未来发现提供了 FCD 设计。
