Novel Aryl Hydrocarbon Receptor Isoform,AhR2,in Avian Species:Functional Characterization and Evolutionary History

摘要

The aryl hydrocarbon receptor(AhR)mediates various toxic effects induced by dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD).Although there are dramatic differences in sensitivity to dioxin toxicity among avian species,information on molecular characterization of avian AhR is limited.In our previous study,two distinct AhR isoforms,designated as AhR1 and AhR2 were identified from black-footed albatross(Phoebastria nigripes)and common cormorant(Phalacrocorax carbo),while the presence of multiple AhR isoform has previously been reported only in fish among vertebrates.To understand the role of avian AhR isoforms,we investigated the functional characterization of these AhRs.When assessed by velocity sedimentation,all AhR isoforms from albatross and cormorant exhibited enough sensitivity for the specific binding to[~3H]TCDD,as shown in chicken AhR.An in vitro reporter gene assay using COS-7 cells revealed that AhR2s induce less transcriptional activation via a xenobiotic response element following TCDD exposure,while AhR ls markedly enhanced transactivation.The comparison of hepatic expression levels of total AhR expression reveals that AhRl is the dominant form of avian AhRs.These results are in contrast to fish AhR2,which is a major form in terms of the TCDD-induced responses and mRNA expression.Comparative analysis of gene synteny among bird and other vertebrates suggests that avian and fish AhR2s are derived from independent genome duplications from a single AhR2 gene in a common ancestor,following the divergence of fish and other vertebrate lineages.