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 have examined 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. We have found that Nematostella has a seven-gene cluster comprising three bona fide Hox genes, four Hox-related genes, and a separate two-gene ParaHox cluster. There appear to be seven bona fide Hox genes in Nematostella belonging to the Hox1, Hox2, and Hox9-14 subfamilies, and they are expressed in three distinct domains that collectively span almost the entire primary body axis. Finally, phylogenetic evidence suggests that the Hox and ParaHox clusters may have formed through a series of independent tandem gene duplications and not necessarily via a cluster duplication. Collectively, these data suggest that at least a rudimentary Hox code was operative in the cnidarian-bilaterian ancestor and that it played a role in patterning the animals primary body axis (and possibly the secondary body axis as well). Moreover, strong stabilizing selection has been operating on this Hox code, maintaining certain core characteristics despite being deployed in a bewildering array of animal forms for over half a billion years. ? ? 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 contains 1,056 full-length homeodomain-containing sequences, 37 experimentally-derived structures, 81 homeodomain protein-protein interactions, 84 homeodomain binding sites, and 114 homeodomain proteins implicated in human genetic disorders. A new release of the database providing additional functionality will be released by years end; this new release will include biological pathway information, information on single nucleotide polymorphisms found in homeodomain proteins, and a new query builder that will allow users to issue queries across data sets and generate custom multiple sequence alignments. The Homeodomain Resource is freely available at http:research.nhgri.nih.govhomeodomain.
