It is now well-accepted that there is a Hox code that is partially responsible for patterning the primary body axis in a phylogenetically diverse range of animals; the extensive similarity among Hox expression patterns in a wide range of taxa has led to the recognition that a Hox code might be a fundamental developmental mechanism in animals. These Hox genes are located in conserved genomic clusters across a range of bilaterian animals, suggesting strong stabilizing selection. Over evolutionary time, the functional diversification of Hox genes has clearly contributed to the diversification of animal body plans, so understanding the origin and evolution of Hox genes could prove critical to understanding the metazoan radiation. To investigate the origin and early evolution of Hox genes and the Hox code, we continue to examine several aspects of the sea anemone Nematostella vectensis, a member of the phylum Cnidaria. Since cnidarians constitute an outgroup to the Bilateria, thse organisms can provide unique insights into early Hox evolution. ? ? The subkingdom Bilateria encompasses the overwhelming majority of animals, including all but four early-branching phyla: Porifera, Ctenophora, Placozoa, and Cnidaria. On average, these early-branching phyla have fewer cell types, tissues, and organs, and are considered to be significantly less specialized along their primary body axis. As such, they present an attractive outgroup from which to investigate how evolutionary changes in the genetic toolkit may have contributed to the emergence of the complex animal body plans of the Bilateria. We have made genome-scale comparisons between bilaterians and these early-diverging taxa, considering these data in the context of how they may explain the evolutionary development of primary body axes and axial symmetry across the Metazoa. We have also re-evaluated the validity and evolutionary genomic relevance of the zootype hypothesis, which defines an animal by a specific spatial pattern of gene expression. Finally, we have extended the hypothesis that Wnt genes may be the earliest primary body axis patterning mechanism by suggesting that Hox genes were co-opted into this patterning network prior to the last common ancestor of cnidarians and bilaterians.? ? As an outgrowth of our studies on the homeodomain class of proteins, we have developed and continue to maintain the Homeodomain Resource. The Resource is organized in a compact form and provides user-friendly interfaces for both querying and assembling customized datasets. The current release, which now covers 15 species, contains 1,125 protein-coding genes, 65 pseudogenes, 93 three-dimensional structures, 185 homeodomain proteins implicated in human genetic disorders, 53 homeodomain proteins with documented allelic variants, 103 homeodomain-DNAbinding sites, and 101 protein-protein interactions involving homeodomain proteins. The Homeodomain Resource is freely available at http:/research.nhgri.nih.gov/homeodomain/.
