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Optimal Regulatory Circuit Topologies for Fold-Change Detection.
Miri Adler1, Pablo Szekely1, Avi Mayo1
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Systems
|January 17, 2017
Summary
Evolution favors few regulatory circuits for functions like fold-change detection (FCD). Minimal FCD designs balance speed, noise, and amplitude, explaining evolutionary convergence and guiding synthetic biology.
Area of Science:
- Systems Biology
- Evolutionary Biology
- Synthetic Biology
Background:
- Biological systems often utilize a limited set of regulatory circuit designs for specific functions, a phenomenon known as evolutionary convergence.
- Understanding the reasons behind this convergence on a few optimal designs is crucial for deciphering biological network complexity.
- Fold-change detection (FCD) is a critical biological function involving responses to relative input changes, with two known recurring circuit types.
Purpose of the Study:
- To investigate why evolution repeatedly selects only a few specific regulatory circuit topologies for a given biological function.
- To identify and analyze circuits capable of fold-change detection (FCD) within a comprehensive set of three-node network topologies.
- To determine if known biological FCD circuits represent optimal solutions balancing key performance trade-offs.
Main Methods:
- Conducted an analytical screen of approximately 500,000 three-node circuit topologies.
- Evaluated each topology for its capacity to perform fold-change detection (FCD).
- Assessed the identified FCD circuits based on optimal trade-offs between speed, noise resistance, and response amplitude.
Main Results:
- Fold-change detection (FCD) capability was found to be rare among the screened topologies, yet hundreds of such circuits exist.
- The two previously identified biological FCD circuits (incoherent feedforward and non-linear integral-feedback) were among the minimal optimal designs.
- These optimal circuits demonstrated a superior balance of speed, noise resistance, and response amplitude compared to other FCD topologies.
Conclusions:
- The study provides a framework for understanding evolutionary convergence on minimal, optimal circuit designs for specific biological functions like FCD.
- The findings highlight that known biological FCD circuits are highly optimized solutions.
- The identified FCD circuit designs can inform future synthetic biology endeavors and the discovery of novel biological circuits.
Keywords:
Pareto optimalityS-systemsdesign principlesintegral feedbackmathematical modelmulti-taskingnumerical screenscale invariancesynthetic circuitsMore Related Videos
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