Evolution & Development Group
Evolution of regulatory elements
Using a computational method developed in our lab, we identified phylogenetically conserved noncoding elements (PCNEs) in a manner that is not biased by rearrangement and duplication. We identified more than a thousand PCNEs that have been conserved between vertebrates and the basal chordate amphioxus. Via transgenic zebrafish assays we found that the majority of the computationally identified elements are functional enhancers. We could show that PCNEs are enriched around genes with ancient synteny conservation and that this association is strongest for extragenic PCNEs, suggesting that cis-regulatory interdigitation plays a key role in repressing genome rearrangement. Our results also demonstrate that subfunctionalization of conserved cis-regulation has not been the primary determinate of gene duplicate retention in vertebrates. Instead, the data supports the gene balance hypothesis, which proposes that duplicate retention has been driven by selection against dosage imbalances in genes with many protein connections.