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Background   Wnt5  genes belong to the large  Wnt  family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that  Wnt5  gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two  Wnt5  paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics.    Results  In this study, the phylogeny of  Wnt5  genes was investigated in species belonging to  protostomia  and  deuterostomia . Furthermore, an  in silico  regulatory region analysis of  Wnt5  paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the  Wnt5  gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind.    Conclusions  Results and observations presented in this study, allow us to conclude that during evolution, the  Wnt5  gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the  Wnt5  orthologs do not share the same function during pancreas development. As a final remark, we suggest that an  in silico  comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs.    Reviewers  This article was reviewed by Sarath Janga (nominated by Sarah Teichmann), Ran Kafri (nominated by Yitzhak Pilpel), and Andrey Mironov (nominated by Mikhail Gelfand).

biology direct

Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of a regulatory module with putative implication in pancreas development