Evolution of the gene families forming the Pax/Six regulatory network: isolation of genes from primitive animals and molecular phylogenetic analyses.

Some members of the Pax (paired box) and Six (sine oculis homeobox) gene families function as components of a gene regulatory network controlling eye development. To investigate the early evolution of the genetic interaction between Pax and Six genes, we identified and sequenced members of the Pax and Six gene families from primitive animals. Molecular phylogenetic analyses of the two gene families revealed that all gene duplications that gave rise to different subfamilies occurred before the divergence of cnidarians (ctenophorans) and bilaterians and most of these duplications antedate the sponge-eumetazoan split. Based on the fact that members of Six-1/2 subfamily have genetic interactions with several types of Pax genes from three different subfamilies, it is possible that transcriptional regulation between the Pax and Six genes was established in the common ancestor of all metazoans.