Superfund Research Program
Mechanisms of Resistance of Aquatic Vertebrate Populations to Mixtures
Project Leader: Isaac I. Wirgin
Grant Number: R01ES015447
Funding Period: 2006-2009
The Hudson River (HR) Estuary contains Superfund sites for PCBs, TCDD, and heavy metals. Atlantic tomcod from the HR bioaccumulate high tissue burdens of these contaminants, sometimes to record levels. Wirgin and his research team had previously used tomcod as a model to evaluate the ecological effects of these pollutants and to study the mechanistic bases of their toxicities. Tomcod from throughout the HR are highly resistant to environmentally relevant doses of coplanar PCBs and TCDD, but not PAHs, at a variety of molecular and organismic endpoints including early life stage toxicities and aryl hydrocarbon receptor (AHR) pathway-mediated gene expression. The overall objectives of this project were to further describe the extent of resistance in the HR tomcod population and to characterize its mechanistic basis.
The research team found that Atlantic tomcod Microgadus tomcod from the contaminated Hudson River, New York, are highly resistant to the early life stage toxic effects of four coplanar PCBs and TCDD exposure, but not to that of two PAHs, benzo[a]pyrene or beta-napthoflavone. Similarly, cytochrome P4501A (CYP1A) mRNA induction was highly inducible by these PAHs in tomcod from the Hudson River, but not by coplanar PCBs or TCDD. In contrast, tomcod from cleaner reference rivers were highly sensitive to these toxic effects and CYP1A induction by both all three classes of aromatic hydrocarbons. Therefore, it was of interest to determine the mechanistic basis of this refractory phenotype in Hudson River tomcod. The research team used two different approaches to address this issue; an open-ended microarray approach and a candidate gene approach focusing on the aryl hydrocarbon receptor 2 (AHR2) pathway. They investigated gene expression and gene structure of AHR2 pathway components because it is known to mediate early life stage toxicities of PCB and TCDD exposure and AHR2 knockdowns previously tested in other fishes were refractory to these toxicities.
For the first time, the research team identified the mechanistic basis of resistance to contaminants in any vertebrate population. Furthermore, they demonstrated that resistance to PCBs and possibly other related contaminants can occur remarkably rapidly in highly impacted populations. It is likely that this occurred within 50-100 generations within the Hudson River population—far more rapidly than the thousands of generations previously thought to be required. Such rapid evolution suggests that the selective pressure for the resistant phenotype must have been intense in the Hudson River population. Furthermore, this was the first study to demonstrate that such a dramatic phenotypic change can be due to one genetic change at a single gene locus. This underlying change restricted to a single genetic locus is probably why this evolutionary change was so rapid.