Human developmental enhancers conserved between deuterostomes and protostomes

Area of Science:

• Evolutionary Developmental Biology
• Comparative Genomics
• Molecular Evolution

Background:

• Homologies are key to understanding shared biological principles and animal evolution.
• Conserved transcription factors and signaling pathways form a common developmental toolkit in deuterostomes and protostomes.
• Previous research identified conserved genes but not conserved regulatory sequences between these major animal clades.

Purpose of the Study:

• To identify and characterize the first conserved regulatory sequences between deuterostomes and protostomes.
• To investigate the sequence conservation and functional significance of these novel elements.
• To explore the implications for understanding cis-regulatory evolution in bilaterians.

Main Methods:

• Bioinformatic analysis to identify conserved sequences across deuterostome and protostome genomes.
• Sequence analysis to determine conserved transcription factor binding sites.
• Functional assays to test enhancer activity in vivo, specifically in the vertebrate central nervous system.

Main Results:

• Discovery of the first conserved enhancers, termed bilaterian conserved regulatory elements (Bicores).
• Bicores exhibit sequence conservation and conserved gene synteny.
• Sequence conservation reflects conserved transcription factor binding sites, indicating functional conservation.
• Bicores function as developmental enhancers, driving expression of transcriptional repressors in the vertebrate CNS.

Conclusions:

• Bicores represent the first identified conserved regulatory sequences bridging deuterostomes and protostomes.
• Their conservation suggests a deeper layer of regulatory conservation than previously recognized.
• The limited number of Bicores implies significant cis-regulatory rewiring but highlights potential for future discoveries with improved understanding and broader genomic sampling.