Mechanistic Basis of Resistance to PCBs in Atlantic Tomcod from the Hudson River

Chronic pollution of the Hudson River, New York, results in rapid evolution of resistance to the pollutants. 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.

[1]  G. Perdew,et al.  Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization. , 1999, Biochemistry.

[2]  Q. Ma,et al.  Induction of CYP1A1. The AhR/DRE paradigm: transcription, receptor regulation, and expanding biological roles. , 2001, Current drug metabolism.

[3]  S. Courtenay,et al.  Evidence of Spatially Extensive Resistance to PCBs in an Anadromous Fish of the Hudson River , 2005, Environmental health perspectives.

[4]  William F Morris,et al.  Aging in the Natural World: Comparative Data Reveal Similar Mortality Patterns Across Primates , 2011, Science.

[5]  M. E. Hahn,et al.  Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Kennedy,et al.  The molecular basis for differential dioxin sensitivity in birds: role of the aryl hydrocarbon receptor. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. E. Hahn,et al.  Aryl hydrocarbon receptor polymorphisms and dioxin resistance in Atlantic killifish (Fundulus heteroclitus). , 2004, Pharmacogenetics.

[8]  Richard E Peterson,et al.  Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  M. Ikonomou,et al.  Spatial variation in hepatic levels and patterns of PCBs and PCDD/Fs among young-of-the-year and adult Atlantic tomcod (Microgadus tomcod) in the Hudson River estuary. , 2004, Environmental science & technology.

[10]  K. Squibb,et al.  Effects of prior exposure history on cytochrome P4501A mRNA induction by PCB congener 77 in atlantic Tomcod , 1992 .

[11]  M. E. Hahn,et al.  Developmental and tissue-specific expression of AHR1, AHR2, and ARNT2 in dioxin-sensitive and -resistant populations of the marine fish Fundulus heteroclitus. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  S. Courtenay,et al.  Comparison of hepatic and extra hepatic induction of cytochrome P4501A by graded doses of aryl hydrocarbon receptor agonists in Atlantic tomcod from two populations. , 2006, Aquatic toxicology.

[13]  E. Glover,et al.  Analysis of the four alleles of the murine aryl hydrocarbon receptor. , 1994, Molecular pharmacology.

[14]  K. Able,et al.  The First Year in the Life of Estuarine Fishes in the Middle Atlantic Bight , 1998 .

[15]  D. Nacci,et al.  Adaptation of the Estuarine Fish Fundulus heteroclitus (Atlantic Killifish) to Polychlorinated Biphenyls (PCBs) , 2010 .

[16]  S. Kennedy,et al.  Key amino acids in the aryl hydrocarbon receptor predict dioxin sensitivity in avian species. , 2008, Environmental science & technology.

[17]  C. Bradfield,et al.  ARA9 Modifies Agonist Signaling through an Increase in Cytosolic Aryl Hydrocarbon Receptor* , 2000, The Journal of Biological Chemistry.