Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework

Area of Science:

• Evolutionary biology
• Genomics
• Molecular biology

Background:

• Cis-regulatory changes are a key driver of animal morphological diversity.
• Genome-wide studies reveal complexities and paradoxes in enhancer evolution.
• Current understanding of cis-regulatory evolution mechanisms is incomplete.

Purpose of the Study:

• To propose an integrative evolutionary framework for cis-regulatory evolution.
• To identify key premises for the origin of novel enhancer activity.
• To re-evaluate existing data on cis-regulatory evolution.

Main Methods:

• Theoretical framework development based on molecular and organizational constraints.
• Analysis of existing comparative cis-regulatory data.
• Discussion of evolutionary mechanisms in light of the proposed model.

Main Results:

• Novel enhancer activity originates from accessible chromatin environments.
• Compatibility with 3D genome structure and existing cis-regulatory element (CRE) interactions is crucial.
• Mechanisms not meeting these premises contribute less to regulatory evolution.

Conclusions:

• The proposed framework integrates molecular and genomic constraints for enhancer evolution.
• Overprinting of ancestral CREs and exaptation of transposable elements are key evolutionary mechanisms.
• A deeper mechanistic understanding is needed for cis-regulatory evolution.