Reconstructing the evolutionary history of Hox cluster origins will lead to 
insights into the developmental and evolutionary significance of Hox gene 
clusters in vertebrate phylogeny and to their role in the origins of various 
vertebrate body plans. We have isolated two Hox clusters from the horn shark, 
Heterodontus francisci. These have been sequenced and compared with one another 
and with other chordate Hox clusters. The results show that one of the horn 
shark clusters (HoxM) is orthologous to the mammalian HoxA cluster and shows a 
structural similarity to the amphioxus cluster, whereas the other shark cluster 
(HoxN) is orthologous to the mammalian HoxD cluster based on cluster 
organization and a comparison with noncoding and Hox gene-coding sequences. The 
persistence of an identifiable HoxA cluster over an 800-million-year divergence 
time demonstrates that the Hox gene clusters are highly integrated and 
structured genetic entities. The data presented herein identify many noncoding 
sequence motifs conserved over 800 million years that may function as genetic 
control motifs essential to the developmental process.