The increasing availability of genomic data for non-mammalian organisms and similarities to the human genome underscore the value of these organisms as models of a variety of diseases in humans (Aparicio et al. 2002; Dehal et al. 2002; Ballatori et al. 2003) . The identification of conserved coding and regulatory regions is enhanced by including divergent sequences in comparative studies (Thomas et al. 2003 ) because these sequences provide more stringent filters for detecting conserved, and presumably functionally important elements (Dubchak et al. 2000; Thomas et al. 2003; Ahituv et al. 2004) . Consequently, sequences from evolutionarily distant marine vertebrates and protovertebrates are being used in comparative studies with increasing frequency. The pufferfish (Fugu rubripes) genome sequencing project supported this approach as it led to the discovery of nearly 1000 human genes not previously described (Aparicio et al. 2002) . Sequence comparisons of the Hoxb-4 gene in mouse and Fugu identified novel regulatory elements that directed subsets of the full Hoxb-4 expression pattern in transgenic mice (Aparicio et al. 1995; Amores et al. 2004) . In a recent comparative analysis of the HoxA cluster in human, horned shark and zebrafish (Chiu et al. 2002) , extensive conservation of non-coding sequence motifs was found between the human and shark sequences, whereas zebrafish sequences exhibited significant loss of conservation. The majority of newly identified regulatory elements for this cluster of genes were identical to known binding sites for regulatory proteins as defined in the transcription factor database, TRANSFAC (http://www.biobase.de; Matys et al. 2003) , demonstrating the accuracy of this approach (Matys et al. 2003; Santini et al. 2003) .