A spectrum of modularity in multi‐functional gene circuits

• Published in: Molecular systems biology 2017-04, Vol.13 (4), p.925-n/a
• Main Authors: Jiménez, Alba, Cotterell, James, Munteanu, Andreea, Sharpe, James
• Format: Article
• Language: English
• Subjects: Algorithms; Behavior; Circuits; decomposability; dynamical mechanism; EMBO26; EMBO33; EMBO37; Equilibrium; Functional morphology; Functionals; gene circuits; Gene expression; Gene Regulatory Networks; Hybrid circuits; Models, Genetic; Modular systems; Modularity; Modules; multi‐functionality; Neural networks; Structure-function relationships; Systems Biology - methods
• ISSN: 1744-4292; 1744-4292
• 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: hybrid circuits which overlay two simpler mono‐functional sub‐circuits within their circuitry, and emergent 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. Synopsis A computational survey of simple bi‐functional gene circuits reveals a spectrum of possible modularity. While many circuits are decomposable into sub‐modules, others are not. These non‐modular, non‐intuitive circuits may be just as common in nature. A wide range of simple wiring designs is computationally screened to find circuits capable of two distinct patterning functions: lateral inhibition and lateral induction. While some of these bi‐functional circuits contain clear function‐specific sub‐modules (hybrids), many other circuits do not (emergent). The distinction between hybrid circuits and emergent circuits can be seen in their dynamics, as well as their structure. Although emergent circuits are less intuitive and harder to understand than modular ones, they are just as robust, and thus equally biologically plausible. Graphical Abstract A computational survey of simple bi‐functional gene circuits reveals a spectrum of possible modularity. While many circuits are decomposable into sub‐modules, others are not. These non‐modular, non‐intuitive circuits may be just as common in nature.