Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria

Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in p atterning the anterior-posterior (AP) axis. This set includes the well-stud ied Hox cluster genes, and the recently described genes of the ParaHox clus ter, which is believed to be the evolutionary sister of the Hox cluster ( B rooke et al. 1998). The conserved role of these axial patterning genes in a nimals as diverse as frogs and flies is believed to reflect an underlying h omology (i.e., all bilaterians derive from a common ancestor which possesse d an AP axis and the developmental mechanisms responsible for patterning th e axis). However, the origin and early evolution of Hox genes and ParaHox g enes remain obscure. Repeated attempts have been made to reconstruct the ea rly evolution of Hox genes by analyzing data from the triphoblastic animals , the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient informat ion from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfi shes, and sea anemones). In combination with outgroup taxa, another potenti al source of information about Hox origins is outgroup genes (e.g., the gen es of the ParaHox cluster). In this article, we present cDNA sequences of t wo Hox-like genes (anthox2 and anthox6) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (=Cnox2) is homolog ous to the GSX class of ParaHox genes, and anthox6 is homologous to the ant erior class of Hox genes. Therefore, the origin of Hox genes and ParaHox ge nes occurred prior to the evolutionary split between the Cnidaria and the B ilateria and predated the evolution of the anterior-posterior axis of bilat erian animals. Our analysis also suggests that the central Hox class was in vented in the bilaterian lineage, subsequent to their split from the Cnidar ia.