Intersecting transcription networks constrain gene regulatory evolution.

Area of Science:

• Evolutionary biology
• Systems biology
• Genetics

Background:

• Epistasis (non-additive genetic interactions) significantly constrains evolutionary trajectories.
• The impact of epistasis on the evolution of biological networks, like transcription circuits, remains poorly understood.

Purpose of the Study:

• To investigate the evolutionary pathways of a yeast transcription network regulating mating pheromone response.
• To understand how epistasis influences the evolution of transcription factor DNA binding modes.

Main Methods:

• Reconstruction of ancestral states and evolutionary intermediates.
• Analysis of transcription regulator Ste12 binding mechanisms.
• Examination of interactions between overlapping transcription networks.

Main Results:

• The transcription regulator Ste12 evolved two distinct DNA-binding modes across different yeast lineages.
• Direct DNA binding by Ste12 was not accessible to the ancestral state.
• Evolution of direct binding was dependent on a prior lineage-specific alteration in a cell-type specification network.

Conclusions:

• The evolution of cis-regulatory regions is constrained by their position within interconnected biological networks.
• Understanding network context is crucial for predicting evolutionary pathways and the impact of epistasis.