Project 4

Mechanisms and Impacts of PCB Resistance in Fish

Project 4 seeks to understand the population-level impacts of long-term exposure to Superfund chemicals by elucidating the molecular mechanisms of evolved resistance of fish to halogenated aromatic hydrocarbons (HAHs, including polychlorinated biphenyls (PCBs)) and polynuclear aromatic hydrocarbons (PAHs).

scorton fish collection

Project Leaders

Mark E. Hahn, Project Leader
Woods Hole Oceanographic Institution

Sibel I. Karchner, Co-Leader
Woods Hole Oceanographic Institution

Project Description

The overall objective of Project 4 is to understand how early life exposure to contaminants at Superfund sites can have profound, long-term impacts on natural populations. To do this, we are studying populations of Atlantic killifish Fundulus heteroclitus that have evolved resistance to polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAHs) and thus are able to live in highly contaminated sites along the Atlantic coast. For example, killifish living at the New Bedford Harbor, MA (NBH) Superfund site (highly contaminated with PCBs) are much less sensitive to effects of PCBs and other halogenated aromatic hydrocarbons (HAHs) than are fish from clean sites. We showed recently that, in addition to resistance to dioxin-like (non-ortho-substituted) PCBs (DL-PCBs), NBH killifish also appear to have reduced sensitivity to non-dioxin-like (ortho-substituted) PCBs (o-PCBs).  Our previous research has implicated the aryl hydrocarbon receptor (AHR) signaling pathway in the mechanism of PCB and PAH resistance in killifish from NBH and other Superfund sites.  Our recent population genomic study of multiple sensitive and resistant killifish populations demonstrated specific genetic changes (selection) in the four AHR loci in killifish as well as in another AHR pathway gene, AHR-interacting protein (AIP). We hypothesize that the evolution of resistance to PCBs involves additive or epistatic interactions between multiple components of the AHR pathway, including AIP and one or more of the four AHRs in killifish.

In the current project, to investigate the role of AHRs and AIP in the evolved resistance to DL-PCBs, we are using CRISPR-Cas9 genome-editing technology to generate AIP-deficient lines of killifish and zebrafish. We will determine whether loss of AIP affects embryonic development of zebrafish and the sensitivity of embryos and larvae to PCBs. We will also examine PCB-sensitive and –resistant populations of fish for AIP variants (single-nucleotide polymorphisms (SNPs)) that may be involved in the mechanism of resistance, and then test the role of the SNPs by using CRISPR-Cas9 to knock-in each SNP into the zebrafish AIP locus. The AIP-mutant zebrafish generated by this research, and AIP-mutant killifish whose generation is initiated in these studies, will be used in future research to elucidate the role of AIP in the toxicity and evolved resistance to both DL-PCBs and o-PCBs.

This study will help elucidate the role of the AHR pathway in animals and the long-term ecological effects of Superfund chemicals.

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