Xenobiotic Response Genes in the Midwater Fish Sigmops elongatum

A region of the global ocean of growing interest is the midwater or mesopelagic region, the so-called “ocean twilight zone” (OTZ). Fishes of the OTZ represent an abundant biomass, important to open oceanic energy dynamics. The OTZ is threatened by exploitation, and by effects of globally distributed organic pollutants. Of particular concern are chemicals that act through the aryl hydrocarbon receptor (AHR). These occur in tissues of mid-water fishes, including in areas impacted by oil spills, at levels that could elicit toxic responses. Understanding functional properties of the ligand-activated AHR pathway of detoxification in mid-water fishes, including AHR, cytochrome P4501A (CYP1A) and P450 reductase (POR), is important for assessing chemical effects in the remote OTZ. Prior studies indicated induction of CYP1A mRNA, protein and catalytic activity in midwater fishes. Here we examine structures of AHR, CYP1A and POR cloned from a cosmopolitan midwater species, Sigmops elongatum, to assess possible adaptation to changing pressures associated with diurnal migrations. Both AHR and CYP1A are hydrophobic-ligand binding proteins, and CYP1A and POR are membrane-bound protein partners, targets for pressure adaptation. Positionally unique amino acid substitutions were widespread in the primary structures of all three proteins in comparison to hundreds of vertebrate orthologs. 3-D modeling shows that substitutions occur both at predicted buried and solvent-exposed sites, sometimes in functional domains in AHR (e.g. the ligand binding domain) and POR (the NADP binding domain) but not in substrate-recognition sites of CYP1A. Notably, the amino acid structures of S. elongatumproteins contrast with the orthologs in the abyssal fish Coryphaenoides armatus), indicating differences in molecular adaptation to pressure. (USA-UK Fulbright Scholarship, a Royal Society grant, NIH Superfund grant 5P42ES007381, and NIH grant 5U41HG003345)