title: Mechanistic basis of resistance to PCBs in Atlantic tomcod from the Hudson River.
abstract: The mechanistic basis of resistance of vertebrate populations to contaminants, including Atlantic tomcod from the Hudson River (HR) to polychlorinated biphenyls (PCBs), is unknown. HR tomcod exhibited variants in the aryl hydrocarbon receptor 2 (AHR2) that were nearly absent elsewhere. In ligand-binding assays, AHR2-1 protein (common in the HR) was impaired as compared to widespread AHR2-2 in binding TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and in driving expression in reporter gene assays in AHR-deficient cells treated with TCDD or PCB126. We identified a six-base deletion in AHR2 as the basis of resistance and suggest that the HR population has undergone rapid evolution, probably due to contaminant exposure. This mechanistic basis of resistance in a vertebrate population provides evidence of evolutionary change due to selective pressure at a single locus.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine,Tuxedo, NY 10987, USA. Isaac.wirgin@nyumc.org
authors.forename: Isaac
authors.initials: I
authors.lastname: Wirgin
authors.forename: Nirmal K
authors.initials: NK
authors.lastname: Roy
authors.forename: Matthew
authors.initials: M
authors.lastname: Loftus
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Chambers
authors.forename: Diana G
authors.initials: DG
authors.lastname: Franks
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hahn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000235:genetics; D004351:Drug Resistance; D019143:Evolution, Molecular; D048388:Gadiformes / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D005787:Gene Frequency; D017930:Genes, Reporter; D006239:Haplotypes; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009518:New York; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D045483:Rivers; D012641:Selection, Genetic; D017384:Sequence Deletion; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D004272:DNA, Mitochondrial; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl