Publication Date:
2022-05-26
Description:
© The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Current Opinion in Toxicology 2 (2017): 58-71, doi:10.1016/j.cotox.2017.02.003
Description:
The aryl hydrocarbon receptor (AHR) was for many years of interest only to pharmacologists and toxicologists. However, this protein has fundamental roles in biology that are being revealed through studies in diverse animal species. The AHR is an ancient protein. AHR homologs exist in most major groups of modern bilaterian animals, including deuterostomes (chordates, hemichordates, echinoderms) and the two major clades of protostome invertebrates [ecdysozoans (e.g. arthropods and nematodes) and lophotrochozoans (e.g. molluscs and annelids)]. AHR homologs also have been identified in cnidarians such as the sea anemone Nematostella and in the genome of Trichoplax, a placozoan. Bilaterians, cnidarians, and placozoans form the clade Eumetazoa, whose last common ancestor lived approximately 600 million years ago (MYA). The presence of AHR homologs in modern representatives of all these groups indicates that the original eumetazoan animal possessed an AHR homolog. Studies in invertebrates and vertebrates reveal parallel functions of AHR in the development and function of sensory neural systems, suggesting that these may be ancestral roles. Vertebrate animals are characterized by the expansion and diversification of AHRs, via gene and genome duplications, from the ancestral protoAHR into at least five classes of AHR-like proteins: AHR, AHR1, AHR2, AHR3, and AHRR. The evolution of multiple AHRs in vertebrates coincided with the acquisition of high-affinity binding of halogenated and polynuclear aromatic hydrocarbons and the emergence of adaptive functions involving regulation of xenobiotic-metabolizing enzymes and roles in adaptive immunity. The existence of multiple AHRs may have facilitated subfunction partitioning and specialization of specific AHR types in some taxa. Additional research in diverse model and non-model species will continue to enrich our understanding of AHR and its pleiotropic roles in biology and toxicology.
Description:
M.E.H. and S.I.K are grateful for the long-term support of our AHR research from the National Institute of Environmental Health Sciences (NIEHS) through grants R01ES006272 and P42ES007381 (Superfund Research Program at Boston University). We also acknowledge support from a WHOI Independent Study Award funded by the Andrew W. Mellon Foundation Endowed Fund for Innovative Research. R.R.M. acknowledges support from the NIH National Center for Research Resources RI-INBRE (P20RR016457), National Science Foundation EPSCoR Cooperative Agreement #EPS-1004057, a MDIBL New Investigator Award funded by ME-INBRE (P20RR016463), and NIEHS grant P30ES003828.
Keywords:
Ah receptor
;
Aryl hydrocarbon receptor
;
bHLH-PAS
;
Dioxin
;
Evolution
;
Development
;
Metazoan
;
Vertebrate
;
Fish
;
Genome duplication
;
Gene expression
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
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