Uncovering the principles underlying animal gene regulation

Comparative sequence conservation has been highly successful at producing detailed maps of coding and non-coding genes, under selective constraints, in sequenced genomes. Critically, we have a poor understanding of gene regulation — we cannot predict context-specific expression by studying sequence conservation across species. Recent studies have shown that the enhancers of genes responsible for tissue-specific phenotypes are evolving extremely rapidly and the majority of transcription factor binding sites have arisen in species-specific lineages between vertebrates. Using experimental and computational approaches, we demonstrate 1) gene regulatory network conservation between evolutionarily distant metazoans 2) ‘covert’ enhancers control deeply conserved developmental gene regulatory circuits. Our findings provide instructive examples of how regulatory circuits are rewired and provide key insights to understanding how tissue-specific gene expression patterns can be evolutionarily conserved despite constant flux in regulatory elements.