Evolution of Hes Gene Family in Vertebrates: the Hes5 Cluster Genes Have Specifically Increased in Frogs

Background: hes genes are chordate homologs of Drosophila genes, hairy and enhancer of split, which encode a basic helix-loop-helix (bHLH) transcriptional repressor with a WRPW motif. Various developmental functions of hes genes, including early embryogenesis and neurogenesis, have been elucidated in vertebrates. However, their orthologous relationships remain unclear partly because of less conservation of relatively short amino acid sequences, the fact that the genome was not analyzed as it is today, and species-specific genome duplication. This results in complicated gene names in vertebrates, which are not consistent in orthologs. We previously revealed that Xenopus frogs have two clusters of hes5, named "the hes5.1 cluster" and "the hes5.3 cluster", but the origin and the conservation have not yet been revealed.

Results: Here, we elucidated the orthologous and paralogous relationships of all hes genes of human, mouse, chicken, gecko, zebrafish, medaka, coelacanth, spotted gar, elephant shark and three species of frogs, Xenopus tropicalis (X. tropicalis), X. laevis, Nanorana parkeri, by phylogenetic and synteny analyses. Any duplicated hes5 were not found in mammals, whereas hes5 clusters in teleost were conserved although not as many genes as the three frog species. In addition, hes5 cluster-like structure was found in the elephant shark genome, but not found in cyclostomata.

Conclusion: These data suggest that the hes5 cluster existed in the gnathostome ancestor but became a single gene in mammals. The number of hes5 cluster genes were specifically large in frogs.