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Rapid evolutionary rewiring of a structurally constrained eye enhancer.

Christina I Swanson¹, David B Schwimmer, Scott Barolo

¹Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.

Current Biology : CB

|July 9, 2011

Summary

Evolutionary changes rapidly alter gene regulatory elements like the sparkling enhancer in Drosophila. Despite sequence turnover, essential regulatory information and structural rules are maintained, demonstrating enhancer rewiring over short evolutionary timescales.

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Area of Science:

Developmental biology
Evolutionary genetics
Genomics

Background:

Enhancers are genomic cis-regulatory sequences controlling gene expression.
Enhancer activity relies on transcription factor binding and arrangement.
The sparkling enhancer regulates dPax2 in Drosophila eye development.

Purpose of the Study:

Examine evolutionary changes in the sparkling enhancer's sequence and structure.
Investigate how regulatory inputs and enhancer organization evolve.
Understand constraints on cis-regulatory sequences during evolution.

Main Methods:

Comparative genomics of sparkling enhancer orthologs.
Analysis of transcription factor binding site evolution.
Functional assessment of enhancer activity and regulation.

Main Results:

The sparkling enhancer has undergone significant reorganization during recent evolution.
Regulatory input strengths shift over evolutionary time, with compensation between factors.
Stereotypical spatial relationships ('grammar') of binding sites are conserved despite recent site derivation.
Low binding affinity for Su(H) is crucial for preventing ectopic Notch signaling.

Conclusions:

Rapid DNA sequence turnover does not negate critical cis-regulatory information or structural rules.
Severely constrained cis-regulatory sequences can be rewired over short evolutionary timescales.
Evolutionary dynamics of enhancers involve both sequence turnover and conserved organizational principles.