Evolution of the gene regulatory network of body axis by enhancer hijacking in amphioxus

Abstract

AbstractA central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control morphogenesis during embryonic development, and the underlying molecular mechanism of the GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3 and Lefty. Despite that the GRN retains a conserved function in deuterostomes, the expression patterns ofGdf1/3andNodalare derived in cephalochordate amphioxus, implying a specific rewiring of the GRN in this lineage. Here we examined the regulatory mechanism and evolution of this GRN in amphioxus by functional genetic manipulations. We found that while the amphioxusGdf1/3orthologue shows nearly no expression during embryogenesis, its duplicateGdf1/3-likelinking toLeftyis zygotically expressed in a similar pattern asLefty. Mutant and transgenic analyses revealed thatGdf1/3is no longer crucial for amphioxus axial development. Instead,Gdf1/3-likeassumes this responsibility, likely through hijackingLeftyenhancers. We also showed that amphioxus Nodal has become an indispensable maternal factor to compensate for the loss of maternalGdf1/3expression. We therefore demonstrated a case that the evolution of an ancestral GRN could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in the extant amphioxus, presumably evolving through a stepwise process. The co-expression ofGdf1/3-likeandLeftyachieved by shared regulatory region may have provided developmental robustness during body axis formation in extant amphioxus, which provides a selection-based hypothesis for the phenomena called developmental system drift.