title: Subfunctionalization of peroxisome proliferator response elements accounts for retention of duplicated fabp1 genes in zebrafish.
abstract: In the duplication-degeneration-complementation (DDC) model, a duplicated gene has three possible fates: it may lose functionality through the accumulation of mutations (nonfunctionalization), acquire a new function (neofunctionalization), or each duplicate gene may retain a subset of functions of the ancestral gene (subfunctionalization). The role that promoter evolution plays in retention of duplicated genes in eukaryotic genomes is not well understood. Fatty acid-binding proteins (Fabp) belong to a multigene family that are highly conserved in sequence and function, but differ in their gene regulation, suggesting selective pressure is exerted via regulatory elements in the promoter.
  
  
  
  In this study, we describe the PPAR regulation of zebrafish fabp1a, fabp1b.1, and fabp1b.2 promoters and compare them to the PPAR regulation of the spotted gar fabp1 promoter, representative of the ancestral fabp1 gene. Evolution of the fabp1 promoter was inferred by sequence analysis, and differential PPAR-agonist activation of fabp1 promoter activity in zebrafish liver and intestine explant cells, and in HEK293A cells transiently transfected with wild-type and mutated fabp1promoter-reporter gene constructs. The promoter activity of spotted gar fabp1, representative of the ancestral fabp1, was induced by both PPARα- and PPARγ-specific agonists, but displayed a biphasic response to PPARα activation. Zebrafish fabp1a was PPARα-selective, fabp1b.1 was PPARγ-selective, and fabp1b.2 was not regulated by PPAR.
  
  
  
  The zebrafish fabp1 promoters underwent two successive rounds of subfunctionalization with respect to PPAR regulation leading to retention of three zebrafish fabp1 genes with stimuli-specific regulation. Using a pharmacological approach, we demonstrated here the divergent regulation of the zebrafish fabp1a, fabp1b.1, and fabp1b.2 with regard to subfunctionalization of PPAR regulation following two rounds of gene duplication.
authors.affiliation: Department of Pharmacology, Dalhousie University, 5850 College St, Halifax, NS, B3H 4R2, Canada.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Laprairie
authors.affiliation: Department of Pharmacology, Dalhousie University, 5850 College St, Halifax, NS, B3H 4R2, Canada.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Denovan-Wright
authors.affiliation: Department of Biology, Dalhousie University, 31355 Oxford St, PO Box 15000, Halifax, NS, B3H 4R2, Canada. jmwright@dal.ca.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wright
mesh_terms: D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D020440:Gene Duplication; D005786:Gene Expression Regulation; D020131:Genes, Duplicate; D006801:Humans; D009154:Mutation; D047493:PPAR alpha / Q000235:genetics; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D050556:Fatty Acid-Binding Proteins; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D029961:Zebrafish Proteins
keywords: Dual luciferase assay; Fatty acid-binding protein; Gene promoter evolution; Neofunctionalization; Nonfunctionalization; Peroxisome proliferator activated receptor (PPAR); Spotted gar; Subfunctionalization; Teleost fishes; Zebrafish