Functional resolution of duplicated hoxb5 genes in teleosts.
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.
Jarinova
Olga
O
Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Hatch
Gary
G
Poitras
Luc
L
Prudhomme
Christelle
C
Grzyb
Magdalena
M
Aubin
Josée
J
Bérubé-Simard
Félix-Antoine
FA
Jeannotte
Lucie
L
Ekker
Marc
M
D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D017124:Conserved Sequence; D021901:DNA, Intergenic / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D020131:Genes, Duplicate; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D021901:DNA, Intergenic; D018398:Homeodomain Proteins; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C489127:hoxb5a protein, zebrafish; C489128:hoxb5b protein, zebrafish; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase