How the Structure of Signaling Regulation Evolves: Insights from an Evolutionary Model
Danial Asgari1,2, Ann T Tate1,2
1Department of Biological Sciences, Vanderbilt University, Nashville TN 37232.
Biorxiv : the Preprint Server for Biology
|November 1, 2024
Summary
Negative feedback loops (NFLs) in cell signaling evolve differently based on their position. Downstream NFLs evolve more robustly than upstream NFLs, influencing immune pathway regulation.
Area of Science:
- Evolutionary biology
- Systems biology
- Molecular biology
Background:
- Signaling pathways use negative feedback loops (NFLs) to regulate cellular responses to environmental changes.
- NFLs can function upstream (reducing input) or downstream (reducing output) of signaling cascades.
- Downstream NFLs directly regulate gene expression, unlike upstream NFLs which involve intermediate proteins.
Purpose of the Study:
- To test the hypothesis that downstream NFLs evolve under more stringent selection than upstream NFLs.
- To investigate the evolutionary pressures shaping NFLs within immune signaling pathways.
- To understand how signaling costs and environmental factors influence NFL evolution.
Main Methods:
- Developed a minimal model of immune signaling incorporating negative feedback loops.
- Analyzed evolutionary rates of genes encoding upstream and downstream NFLs.
- Simulated model behavior under varying parameters like signaling cost and protein half-life.
Main Results:
- Genes encoding downstream NFLs exhibit slower evolutionary rates, supporting more stringent selection.
- The model predicts robust evolution of downstream NFLs across parameter changes.
- Upstream NFL evolution is favored by shorter signaling protein half-lives and high infection rates, but not necessarily high signaling costs.
Conclusions:
- Downstream NFLs are robustly evolved regulatory mechanisms in signaling pathways.
- The evolution of upstream NFLs is sensitive to factors like protein stability and host-pathogen dynamics.
- Understanding NFL evolution provides insights into the regulation of biological systems and their adaptation to environmental changes.
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