The aryl hydrocarbon receptor in early vertebrates

Abstract

The Ah receptor (AhR), which mediates effects of dioxins and related halogenated aromatic hydrocarbons, belongs to the emerging bHLH-PAS family of transcription factors. A reverse-transcription-polymerase chain reaction (RT-PCR) method using degenerate primers was used to search for the AhR in early vertebrates, including bony, cartilaginous, and jawless fish. AhR cDNA sequences were obtained for the killifish Fundulus heteroclitus, smooth dogfish Mustelus canis, the little skate Raja erinacea and the sea lamprey Petromyzon marinus. Further studies revealed evidence for a second AhR gene (AHR2) in Fundulus and Mustelus. The fish AhR1 and AhR2 genes are as different from each other as each is from mammalian AhRs, suggesting that they are the result of an ancient gene duplication, possibly occurring prior to the divergence of lineages leading to present-day mammals and fish. These studies demonstrate the conservation of AhR structure over more than 500 million years of vertebrate evolution. A search of the GenBank protein sequence database revealed a possible AhR homolog in the nematode Caenorhabditis elegans. Phylogenetic analysis of fish AhR sequences in comparison to mammalian AhRs and other members of the bHLH-PAS gene family provides an evolutionary perspective to the study of dioxin toxicity and Ah receptor function.