Genomics of Basal Metazoans1

Integrative and Comparative Biology, Sep 2005 by Steele, Robert E

SYNOPSIS.

An in-depth understanding of the biology of animals will require the generation of genomics resources from organisms from all phyla in the metazoan phylogenetic tree. Such resources will ideally include complete genome sequences and comprehensive EST (expressed sequence tag) datasets for each species of interest. Of particular interest in this regard are animals in the early diverging non-bilaterian phyla Porifera, Placozoa, Cnidaria, and Ctenophora. Publications describing the results from the use of genomics approaches in these phyla have only recently begun to appear (Kortschak et al., 2003; Yang et al., 2003; Steele et al., 2004). Issues to be considered here include choosing the basal metazoan species to examine with genomics approaches, the relative advantages and disadvantages of genome sequencing versus EST projects, and the resources and infrastructure required to carry out such projects successfully.

WHAT CAN ONE EXPECT TO LEARN BY DOING GENOMICS ON BASAL METAZOANS?

Before discussing the issues associated with pursuing genomic studies on basal metazoans, it is important to consider what one can expect to learn from such studies. If the whole genome of an organism is sequenced, one obviously expects ultimately to end up with a catalog of all of the genes for that organism. The value of such a catalog is substantial. It allows one to evaluate critically a number of interesting hypotheses related to evolutionary, physiological, and developmental processes. For example the absence of a gene from a cnidarian genome but its presence in bilaterian genomes could indicate that the gene evolved after the divergence of cnidarians. Alternatively, the gene could have been secondarily lost from cnidarians. To determine which hypothesis is correct one would then need to have information on this gene from other taxa, particularly ones which diverged prior to cnidarians. If, for example, sponges were found to have the gene, then one would conclude that secondary loss explains its absence from cnidarians.

Secondary loss is not as rare as might be expected. Kortschak et al. (2003) have provided a preliminary sampling of the genes in the coral Acropora millepora using an expressed sequence tag dataset of 1,376 clusters and found that 53 of the clusters represented genes that are present in vertebrates but absent from Drosophila and Caenorhabditis elegans. A number of additional cases have been found in which a gene is present in a cnidarian and in deuterostomes, but absent from the protostomes Drosophlla and/or C. elegans (Chan et al., 1994; Steele et al., 1999; Fedders et al., 2004). Thus these genes were apparently lost secondarily from these protostomes. In essence, then, evolution has carried out gene knockout experiments in worms and flies that indicate that these genes are not required for at least some types of metazoans to survive in their natural environments. This gets around the problem with a number of gene knockout studies in mice, in which absence of an observable phenotype may be due either to compensation by paralogous genes or the failure of the laboratory to duplicate the animal's natural environment.

Of particular interest would be genes that are absent from all basal metazoans but present in bilaterians. These would presumably represent genes that were selected for their role in a bilaterian-specific biological process. Proof of such genes would require complete genome sequences of representatives from each of the basal metazoan phyla. Of equal interest to biologists would be genes found only in one or more basal metazoan taxa. These genes would be candidates for involvement in taxon-specific biological processes. Examples of such genes would include those encoding proteins involved in taxon-specific signaling processes (e.g., those involved in reproduction), genes involved in taxon-specific defense against pathogens, genes involved in production of taxon-specific structures (e.g., the nematocysts of cnidarians), and genes involved in taxon-specific symbioses (e.g., coral/algal symbiosis). Having genome sequences from sponges and cnidarians in particular will potentially have far-reaching impacts on fields as diverse as ecology and medicine. For example, our understanding of the phenomenon of coral bleaching (Hughes et al., 2003; Pandolfi et al., 2003) might be enhanced by knowledge of a cnidarian gene set. Our understanding of the synthesis and biological roles of the large number of natural products, some of biomedical relevance, identified in marine cnidarians and sponges (Fingerman and Nagabhushanam, 2001) might also be enhanced by having in hand the sequences of all of the proteins from such organisms, presumably including the enzymes responsible for synthesis of such products.

GENOME SEQUENCING VERSUS ESTs

If one wants to make unequivocal statements about the gene content of an organism, a complete, fully annotated genome sequence is the only acceptable dataset. An alternative approach to obtain information about the gene set of an organism is to generate an EST dataset. ESTs are produced by single pass sequencing from one or both ends of randomly selected clones from a cDNA library (Adams et al., 1992). The presence of a gene in an organism is confirmed if an EST for it is identified even in the absence of a complete genome sequence. However, the absence of a gene can be demonstrated only if the whole genome has been sequenced. Given this requirement, a complete genome sequence from each of the basal metazoan phyla is an obvious goal. In addition, complete genome sequences allow one to ask a variety of important questions related to evolution of genome organization and gene regulation. Some of the advantages and disadvantages of genome projects and EST projects are listed in Table 1.