Protein-coding changes preceded cis-regulatory gains in a newly evolved transcription circuit

Area of Science:

• Evolutionary biology
• Molecular biology
• Genetics

Background:

• Transcriptional circuits evolve through changes in coding sequences of regulators and cis-regulatory elements.
• The coordinated evolution of these components remains poorly understood.

Purpose of the Study:

• To elucidate the evolutionary pathway of a specific transcriptional circuit in fungi involving the homeodomain protein Matα2.
• To investigate how coding changes in a regulator and cis-regulatory sequence changes co-evolved.

Main Methods:

• Comparative genomic analysis across fungal species.
• Phylogenetic analysis of regulatory and cis-regulatory sequences.
• Functional analysis of the Matα2 regulator in species with varying cis-regulatory elements.

Main Results:

• A new transcriptional circuit (a-specific gene repression by Matα2) evolved in fungi.
• Coding changes in the Matα2 regulator occurred millions of years before cis-regulatory sequence changes in its target genes.
• Species with coding changes but lacking cis-regulatory sites demonstrate the necessity of these coding changes for conserved regulator function.

Conclusions:

• The evolution of transcriptional circuits can occur through sequential changes, with coding alterations in regulators preceding cis-regulatory adaptations.
• Deeply conserved functions of regulators, modified by coding changes, can pre-adapt them for novel regulatory roles, facilitating circuit evolution.