New insights from hemichordate genomes: prebilaterian origin and parallel modifications in the paired domain of the Pax gene eyegone.

The evolutionary origin of the Drosophila Pax transcription factor gene eyegone (eyg) has long been enigmatic owing to the failure in detecting orthologs in other species and the unusual N-terminal truncation of the DNA-binding paired domain (PD). Based on the discovery of eyg orthologs in representatives of hemichordate phyla, we show that the origin of eyg predated metazoan diversification and that the PD experienced similar but independent N-terminal modifications in the lineages to sea urchins and insects. Sequence conservation patterns further raise the possibility of persisting functionality in the N-terminal PD of strongly modified eyg orthologs. Finally, we note that the evolutionary histories of eyg and the vertebrate Pax6 isoform 5a, which have been considered functional homologs, are not correlated. Taken together, these findings identify Drosophila eyg as the baptizing member of an ancient Pax gene subfamily and recommend abandoning its classification as Pax6(5a)-related gene.