TFforge utilizes large-scale binding site divergence to identify transcriptional regulators involved in phenotypic...

Area of Science:

• Evolutionary biology
• Genomics
• Molecular biology

Background:

• Gene regulation changes are crucial for evolution, but identifying causative transcription factors (TFs) is difficult.
• Understanding TF roles in phenotypic evolution, especially trait loss, is a key challenge.

Purpose of the Study:

• To present TFforge, a computational method for identifying TFs involved in the loss of phenotypic traits.
• To provide a tool for uncovering gene-regulatory differences underlying phenotypic evolution between species.

Main Methods:

• TFforge screens regulatory genomic regions for TFs with significant binding site divergence in species that lost a trait.
• The method was validated using simulated data representing various regulatory element scenarios.
• TFforge was applied to eye regulatory elements in subterranean mammals to study eye degeneration.

Main Results:

• TFforge successfully identified relevant TFs across diverse simulated evolutionary scenarios.
• Application to subterranean mammals revealed interacting and co-binding eye-related TFs.
• The study provides insights into TFs potentially responsible for eye degeneration in these species.

Conclusions:

• TFforge is a broadly applicable method for identifying TFs driving phenotypic changes.
• The tool aids in unraveling the gene-regulatory mechanisms behind phenotypic evolution and trait loss.