Transcription Factor Promiscuity Drives Regulatory Rewiring and Evolvability in Gene Networks in Bacteria

Area of Science:

• Evolutionary biology
• Genetics
• Microbiology

Background:

• Gene regulatory networks (GRNs) control gene expression and are crucial for cellular function and evolution.
• Understanding how GRNs evolve and adapt is fundamental to deciphering life's complexity.
• Transcription factors (TFs) are key regulators whose functions can evolve, leading to GRN rewiring.

Purpose of the Study:

• To investigate the mechanisms and principles underlying the evolution of gene regulatory networks (GRNs).
• To understand how transcription factor (TF) functions are acquired and how GRNs rewire over evolutionary time.
• To identify factors that make TFs evolvable and predict evolutionary outcomes.

Main Methods:

• Utilized an experimental evolution model system with the soil bacterium Pseudomonas fluorescens.
• Observed transcription factor (TF) rewiring in real time to gain insights into GRN evolution.
• Analyzed hierarchical patterns of TF rewiring, TF recruitment influences, and the role of crosstalk.

Main Results:

• Identified a hierarchical pattern in TF rewiring, with specific regulators acting as 'first responders'.
• Determined that TF expression level and mutational accessibility critically influence recruitment for novel functions.
• Highlighted the role of non-cognate binding (crosstalk) as a source of raw material for adaptive innovation.

Conclusions:

• Evolutionary pathways for GRN rewiring are often constrained and repeatable due to identifiable principles.
• Understanding TF evolvability allows for the prediction and potential direction of evolutionary trajectories.
• Emerging technologies may further transform the study of GRN rewiring and evolvability.