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First published online 2 October 2008
doi: 10.1242/dev.025817

Development 135, 3543-3553 (2008)
Published by The Company of Biologists 2008
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Functional resolution of duplicated hoxb5 genes in teleosts

Olga Jarinova1,2, Gary Hatch1, Luc Poitras1, Christelle Prudhomme3, Magdalena Grzyb1, Josée Aubin3, Félix-Antoine Bérubé-Simard3, Lucie Jeannotte3 and Marc Ekker1,2,*

1 Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
2 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
3 Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Québec G1R 2J6, Canada.

* Author for correspondence (e-mail: mekker{at}uottawa.ca)

Accepted 5 September 2008

The duplication-degeneration-complementation (DDC) model predicts that subfunctionalization of duplicated genes is a common mechanism for their preservation. The additional Hox complexes of teleost fish constitute a good system in which to test this hypothesis. Zebrafish have two hoxb complexes, with two hoxb5 genes, hoxb5a and hoxb5b, the expression patterns of which suggest subfunctionalization of an ancestral hoxb5 gene. We characterized conserved non-coding elements (CNEs) near the zebrafish hoxb5 genes. One CNE, J3, is only retained in the hoxb5a locus, whereas the others, J1 and J2, are present in both hoxb5 loci. When tested individually, the enhancer activity of individual CNEs, including J3, extensively overlapped and did not support a role in subfunctionalization. By contrast, reporter transgene constructs encompassing multiple CNEs were able to target reporter gene expression to unique domains of hoxb5a and hoxb5b expression. The deletion of J3 from the hoxb5a locus resulted in expression that approached that of hoxb5b, whereas its insertion in the hoxb5b locus increased reporter expression and rendered it more similar to that of hoxb5a. Our results highlight the importance of interactions between CNEs in the execution of complementary subfunctions of duplicated genes.

Key words: CNS development, Gene duplication, Mouse embryogenesis, Transcriptional regulation, Zebrafish embryogenesis, cis-acting regulatory elements


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