Bilaterian animals have a Hox gene cluster essential for patterning the main body axis, and a ParaHox gene cluster. Comparison of Hox and ParaHox genes has led workers to postulate that both clusters originated from the duplication of an ancient cluster named ProtoHox, which contained up to four genes with at least the precursors of anterior and posterior Hox/ParaHox genes1,2,3. However, the way in which genes diversified within the ProtoHox, Hox and ParaHox clusters remains unclear because no systematic study of non-bilaterian animals exists. Here we characterize the full Hox/ParaHox gene complements and genomic organization in two cnidarian species (Nematostella vectensis and Hydra magnipapillata), and suggest a ProtoHox cluster simpler than originally thought on the basis of three arguments. First, both species possess bilaterian-like anterior Hox genes, but their non-anterior genes do not appear as counterparts of either bilaterian central or posterior genes; second, two clustered ParaHox genes, Gsx and a gene related to Xlox and Cdx, are found in Nematostella vectensis; and third, we do not find clear phylogenetic support for a common origin of bilaterian Cdx and posterior genes, which might therefore have appeared after the ProtoHox cluster duplication. Consequently, the ProtoHox cluster might have consisted of only two anterior genes. Non-anterior genes could have appeared independently in the Hox and ParaHox clusters, possibly after the separation of bilaterians and cnidarians.
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We thank D. Rokhsar for his efforts in heading the Nematostella Genome project at DoE-JGI, and the J. Craig Venter Institute and the National Human Genome Research Institute for the Hydra Genome Project. The initial EST screen in Nematostella was funded by the Deutsche Forschungsgemeinschaft, and the construction of the Nematostella BAC library was funded by the National Science Foundation (NSF). This is contribution ISEM-2006-37 of the Institut des Sciences de l'Evolution de Montpellier. Author Contributions The project was conceived and the manuscript written by D.C. and U.T. The bioinformatic identification and genomic assemblies of the homeobox gene complement in the Hydra and Nematostella genome datasets were conducted by D.C. The software package including MàD was written by P.C., who conceived and trained it with D.C. The phylogenetic analyses were performed by F.D. R.B.E. also participated in the homeobox gene classification and phylogenetic analysis. The cloning of cDNAs and genomic clones of Hox-related genes was performed by U.T., E.R. and M.F.J.; BAC library screening was conducted by U.T. and E.R.; and BAC colony PCR was performed by M.F.J. The in situ hybridizations were performed by F.R. R.E.S. and U.T. are members of the Nematostella genome consortium, and R.E.S. is a member of the Hydra genome consortium. R.E.S., P.deJ. and U.T. were co-principal investigators on the NSF grant for the generation of the Nematostella BAC library; U.T. collected the animal material and prepared the DNA; and B.Z. generated the BAC library under the supervision of P.deJ.
Sequences have been deposited in GenBank with accession numbers DQ500742–DQ500879. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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Chourrout, D., Delsuc, F., Chourrout, P. et al. Minimal ProtoHox cluster inferred from bilaterian and cnidarian Hox complements. Nature 442, 684–687 (2006). https://doi.org/10.1038/nature04863
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