A Unified Framework to Dissect Robustness, Plasticity, Evolvability and Canalisation of Biological Function

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Bibliográfalaš dieđut
Publikašuvnnas:bioRxiv (Mar 6, 2025)
Váldodahkki: Chakraborty, Debomita
Eará dahkkit: Raghunathan Rengaswamy, Raman, Karthik
Almmustuhtton:
Cold Spring Harbor Laboratory Press
Fáttát:
Liŋkkat:Citation/Abstract
Full text outside of ProQuest
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022 |a 2692-8205 
024 7 |a 10.1101/2025.03.03.641119  |2 doi 
035 |a 3174601252 
045 0 |b d20250306 
100 1 |a Chakraborty, Debomita 
245 1 |a A Unified Framework to Dissect Robustness, Plasticity, Evolvability and Canalisation of Biological Function 
260 |b Cold Spring Harbor Laboratory Press  |c Mar 6, 2025 
513 |a Working Paper 
520 3 |a A unique balance of seemingly contradictory properties like robustness and plasticity, or evolvability and functional canalisation, characterises biological systems. To understand the basis of these properties, we look into gene regulation, which is at the core of biological function. We simulate dynamical models of over 190 million genetic circuits covering all possible three-gene circuit structures. We develop a computational pipeline to classify these circuits into functional clusters by matching the shape of their temporal responses. Thus, we generate a dataset containing circuit structure, parameters and a corresponding functional label. Our key finding is a finite list of 20 functions that three-node genetic circuits can perform. Moreover, the space of structure and parameters for these circuits tend to be primed for responses that stabilise over time following a perturbation. Every structure has the potential to exhibit multifunctionality with a range of 2-17 functions contingent upon parameters. We quantify network degeneracy and show that many structural changes can be made to a circuit without changing its function. We then define three quantities: structural, parametric, and functional diversities. For a pair of circuits in our generated dataset, we derive these diversities and present a unified framework that analyses the four key biological properties: robustness, plasticity, evolvability, and functional canalisation. Using this unified framework, we identify that only 6.5% of network structures are non-plastic, while it is always possible to find parameter sets for every three-node network to exhibit parametric robustness. We identify functionally canalised circuits from structure pairs that can be interchanged for a large number of parameter sets without a change in function. Overall, our framework offers insights into the fundamental organisation of biological networks by thorough analysis of three-node networks.Competing Interest StatementThe authors have declared no competing interest. 
653 |a Circuits 
653 |a Functional plasticity 
653 |a Structure-function relationships 
653 |a Functional morphology 
653 |a Gene regulation 
700 1 |a Raghunathan Rengaswamy 
700 1 |a Raman, Karthik 
773 0 |t bioRxiv  |g (Mar 6, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3174601252/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2025.03.03.641119v1