In March, 2005 the National Human Genome Research Institute of the National Institutes of Health (NIH), USA, announced that it will fund the whole genome sequencing of Raja erinacea. In the announcement of the Skate Genome Sequencing Initiative (http://www.genome.gov/ 13014443), NIH states: 'The skate (related to many species of shark and cartilaginous fish) was chosen because it belongs to the first group of primitive vertebrates that developed jaws, an important step in vertebrate evolution. Other innovations in this group of animals include an adaptive immune system similar to that of humans, a closed and pressurized circulatory system, and myelination of the nervous system. Understanding these systems of the skate at a genetic level will help scientists identify the minimum set of genes that create a nervous system or develop a jaw, possibly illustrating how these systems have evolved in humans, and how they sometimes go wrong.' Chondrichthyes (cartilaginous) fish appeared approximately 450 million years ago. Elasmobranchs comprise most chondrichthyan organisms. They exhibit fundamental vertebrate characteristics, including a recombinatorial immune system (Hinds and Litman 1986; Adelman et al. 2004) , and are also the oldest existing vertebrates with circulatory system-related signaling molecules and receptors such as platelet-derived growth factor and adenosine receptors. The specialized rectal gland of Squalus acanthias, the spiny dogfish shark, has greatly facilitated the study of cystic fibrosis, sodium and chloride secretion (Devor et al. 1995; Lehrich et al. 1995; Forrest 1996; Henson et al. 1997; Lehrich et al. 1998; Silva et al. 1999; Aller et al. 1999; Greger et al. 1999; Waldegger et al. 1999; Ke et al. 2002; Yang et al. 2002) . Unlike many primary cell cultures that dedifferentiate and lose transport polarity immediately after isolation, primary cultures of shark rectal gland tubular cells maintain fully differentiated function and expression of all known receptors, transporters, ion channels and signal transduction pathways in vitro (Valentich and Forrest 1991; Devor et al. 1995; Lehrich et al. 1995; Aller et al. 1999; Greger et al. 1999; Waldegger et al. 1999; Ke et al. 2002; Yang et al. 2002; Mattingly et al. 2004b) . A comparison of the properties of the cloned shark and human cystic fibrosis transmembrane regulator (CFTR) has provided insights into structural domains related to functional differences in the normal and mutant proteins (Marshall et al. 1991) . The spiny dogfish shark CFTR protein is 72% identical to the human ortholog and comparison of the human and shark CFTR sequences revealed conservation of five cyclic AMP-dependent kinase phosphorylation sites and three residues that, when mutated in the human protein, are associated with cystic fibrosis.