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Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus): A phylogenetic and population-based comparison.
Citation:
Holland, E., J. Goldstone, I. Pessah, A. Whitehead, N. Reid, S. Karchner, M. Hahn, D. Nacci, B. Clark, AND J. Stegeman. Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus): A phylogenetic and population-based comparison. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 192:105-115, (2017).
Impact/Purpose:
This manuscript describes lab and field studies that contribute to our understanding of the ecological risks associated with chronic contaminant exposures to wildlife populations. Here, we assessed genetic patterns associated with long-term response to an important class of highly toxic environmental pollutants. We used laboratory studies to characterize variation among laboratory-reared progeny of fish from populations known to vary in their sensitivity to these pollutants to infer mechanisms of toxicity and tolerance. Results of these studies demonstrate the value of molecular tools to diagnose and predict effects of chemical stressors and characterize the mechanisms and costs of toxic and compensatory responses to chemical stressors by wild populations. General impacts from this contribution include improved understanding by managers and scientists of links between human activities, natural dynamics, ecological stressors and ecosystem condition.
Description:
Non-dioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine receptors (RyR), microsomal Ca2+ channels of broad significance. Teleost fish may be important models for NDL PCB neurotoxicity and we used sequencing databases to characterize teleost RyR and FK506 binding protein 12 or 12.6 kDa (genes FKBP1A; FKBP1B), which promote NDL PCB-triggered Ca2+ dysregulation. Particular focus was placed on describing genes in the Atlantic killifish (Fundulus heteroclitus) genome and searching available RNA-sequencing datasets for single nucleotide variants (SNV) between PCB tolerant versus sensitive killifish from New Bedford Harbor (NBH) or Scorton Creek (SC), MA. Consistent with the teleost whole genome duplication (tWGD), killifish have six RyR genes, corresponding to a and b paralogs of mammalian RyR1, 2 and 3. The presence of six RyR genes was consistent in all teleosts investigated including zebrafish. Killifish have four FKBP1; one FKBP1b and three FKBP1a named FKBP1aa, FKBP1ab, likely from the tWGD and a single gene duplicate FKBP1a3 suggested to have arisen in Atherinomorphae. The RyR and FKBP1 genes displayed tissue and developmental stage-specific mRNA expression, and the previously uncharacterized RyR3, herein named RyR3b, and all FKBP1 genes were prominent in brain. We identified a SNV in RyR3b encoding missense mutation E1458D. In NBH killifish, 57% were heterozygous and 28% were homozygous for this SNV, whereas almost all SC killifish (94%) lacked the variant (n≥39 per population). The outlined sequence differences between mammalian and teleost RyR and FKBP1 together with outlined population differences in SNV frequency may contribute to our understanding of NDL PCB neurotoxicity.
