Evolution of lineage-specific functions in ancient cis-regulatory modules

Area of Science:

• Evolutionary biology
• Developmental biology
• Genomics

Background:

• Morphological evolution results from changes in both coding and regulatory sequences.
• The evolution of cis-regulatory modules (CRMs) and novel expression domains remains poorly understood.

Purpose of the Study:

• To reconstruct the evolutionary history of a lens enhancer within a CRM.
• To investigate how CRMs evolve to generate novel gene expression patterns.

Main Methods:

• Comparative sequence analysis of orthologous deuterostome CRM sequences.
• Functional analysis of enhancer activity in zebrafish.
• Identification and characterization of activator and repressor motifs.

Main Results:

• A lens enhancer predates the lens and bilaterian animals.
• Deuterostome flanking regions activate gene expression in the zebrafish lens via an ancient activator site cluster.
• Repressor motifs in flanking regions and core influence species-specific expression levels.
• Ray-finned fish gained lineage-specific activators, enhancing lens enhancer potency.

Conclusions:

• Modification of existing regulatory potential in flanking regions, not the conserved core, drives novel CRM functions.
• This model may explain the emergence of new regulatory functions in complex CRMs.
• Understanding CRM evolution provides insights into morphological innovation.