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Published on: July 6, 2021
Stability depends on positive autoregulation in Boolean gene regulatory networks
Ricardo Pinho1, Victor Garcia2, Manuel Irimia3
1Department of Biology, Stanford University, Stanford, California, United States of America; PhD Program in Computational Biology, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Positive autoregulation is key to stable gene regulatory networks (GRNs). Evolutionary simulations show that robust and stable GRNs predominantly feature positive autoregulatory loops, mirroring findings in eukaryotic transcription factor networks.
Area of Science:
- Systems Biology
- Computational Biology
- Evolutionary Biology
Background:
- Network motifs are fundamental components of biological regulatory systems, such as gene regulatory networks (GRNs).
- Autoregulation, a basic network motif, is linked to properties like bistability, homeostasis, and robustness, but its evolutionary significance remains unclear.
Purpose of the Study:
- To investigate the relationship between autoregulation and network stability and robustness in GRNs.
- To explore the evolutionary selection of autoregulatory motifs and their connection to network robustness using computational models.
Main Methods:
- Utilized Boolean networks, a class of GRN models, to simulate evolutionary processes.
- Conducted evolutionary simulation experiments incorporating mutation and recombination under various selection models.
- Analyzed the correlation between autoregulation and network stability/robustness across simulated generations.
Main Results:
- A positive correlation was observed between autoregulation and network stability/robustness.
- Stable networks consistently exhibited a prevalence of positive autoregulation across all simulated scenarios.
- The findings suggest that evolutionary selection favors positive autoregulation for enhanced network stability.
Conclusions:
- Biological networks, particularly eukaryotic transcription factor networks, are likely dominated by positive autoregulatory loops due to their contribution to stability and robustness.
- The study provides computational evidence supporting the prevalence and importance of positive autoregulation in the evolution of complex biological networks.
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