Jiménez Alba, Cotterell James, Munteanu Andreea, Sharpe James
EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Mol Syst Biol. 2017 Apr 27;13(4):925. doi: 10.15252/msb.20167347.
A major challenge in systems biology is to understand the relationship between a circuit's structure and its function, but how is this relationship affected if the circuit must perform multiple distinct functions within the same organism? In particular, to what extent do multi-functional circuits contain modules which reflect the different functions? Here, we computationally survey a range of bi-functional circuits which show no simple structural modularity: They can switch between two qualitatively distinct functions, while both functions depend on all genes of the circuit. Our analysis reveals two distinct classes: circuits which overlay two simpler mono-functional sub-circuits within their circuitry, and circuits, which do not. In this second class, the bi-functionality emerges from more complex designs which are not fully decomposable into distinct modules and are consequently less intuitive to predict or understand. These non-intuitive emergent circuits are just as robust as their hybrid counterparts, and we therefore suggest that the common bias toward studying modular systems may hinder our understanding of real biological circuits.
系统生物学中的一个主要挑战是理解一个回路的结构与其功能之间的关系，但是如果该回路必须在同一生物体中执行多种不同功能，这种关系会受到怎样的影响呢？特别是，多功能回路在多大程度上包含反映不同功能的模块？在这里，我们通过计算研究了一系列没有简单结构模块化的双功能回路：它们可以在两种性质不同的功能之间切换，而两种功能都依赖于回路的所有基因。我们的分析揭示了两种不同的类型：一类是在其电路中叠加了两个更简单的单功能子回路的回路，另一类则不是。在第二类中，双功能性源于更复杂的设计，这些设计不能完全分解为不同的模块，因此预测或理解起来不太直观。这些非直观的涌现回路与它们的混合对应物一样稳健，因此我们认为，对模块化系统研究的普遍偏见可能会阻碍我们对真实生物回路的理解。
