Abstract
BackgroundPopulations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) exposure in embryos (5 and 10 dpf) and larvae (15 dpf) from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH) Superfund site (PCB-resistant) and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive).ResultsAnalysis using a 7,000-gene cDNA array revealed striking differences in responsiveness to PCB-126 between the populations; the differences occur at all three stages examined. There was a sizeable set of PCB-responsive genes in the sensitive SC population, a much smaller set of PCB-responsive genes in NBH fish, and few similarities in PCB-responsive genes between the two populations. Most of the array results were confirmed, and additional PCB-regulated genes identified, by RNA-Seq (deep pyrosequencing).ConclusionsThe results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure. The results are consistent with genome-wide disruption of AHR-dependent signaling in NBH fish.
Highlights
Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway
NBH fish were essentially refractory to cytochrome P450 1A (CYP1A) induction (1.5- to 3.8-fold change, PCB vs. Dimethyl sulfoxide (DMSO))
The results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure
Summary
Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. One species that has emerged as a valuable model for investigating evolutionary adaptations to chemical exposure is the Atlantic killifish, Fundulus heteroclitus This estuarine teleost has a long history as a subject for research in environmental biology [3,4,5], and studies over the past two decades have identified several populations of this species that have evolved tolerance or resistance to toxic chemicals [6,7]. Evolved resistance of F. heteroclitus to PAHs or HAHs, first noted in Newark, NJ [9,10], has been described in killifish from the Elizabeth River, VA [11,12,13], New Bedford Harbor, MA [14,15], and several more moderately contaminated sites in New England [8,16] At all of these sites, killifish embryos, larvae, and adults are much less sensitive to acute toxicity of HAHs and PAHs as compared to fish from less contaminated reference sites. The results of these studies on PAH/HAH-resistant killifish suggest that certain AHR-regulated genes–or possibly the AHR pathway generally–have become desensitized in the affected populations
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