A significant proportion of mammalian genes are not represented in the genomes of *Drosophila*, *Caenorhabditis* or *Saccharomyces*, and many of these are assumed to have been vertebrate innovations. To test this assumption, we conducted a preliminary EST project on the anthozoan cnidarian, *Acropora millepora*, a basal metazoan. More than 10% of the *Acropora* ESTs with strong metazoan matches to the databases had clear human homologs but were not represented in the *Drosophila* or *Caenorhabditis* genomes; this category includes a surprising diversity of transcription factors and metabolic proteins that were previously assumed to be restricted to vertebrates. Consistent with higher rates of divergence in the model invertebrates, three-way comparisons show that most *Acropora* ESTs match human sequences much more strongly than they do any *Drosophila* or *Caenorhabditis* sequence. Gene loss has thus been much more extensive in the model invertebrate lineages than previously assumed and, as a consequence, some genes formerly thought to be vertebrate inventions must have been present in the common metazoan ancestor. The complexity of the *Acropora* genome is paradoxical, given that this organism contains apparently few tissue types and the simplest extant nervous system consisting of a morphologically homogeneous nerve net.
A brief commentary on the paper is available in Nature News and Views.