Aryl hydrocarbon receptors: diversity and evolution

Hahn, Mark E

doi:10.1016/s0009-2797(02)00070-4

Cited by 642Toxic Organic Pollutants ImpactPharmacogenetics and Drug MetabolismEnvironmental Toxicology and Ecotoxicology

Aryl hydrocarbon receptors: diversity and evolution

Hahn, Mark E·2002·Chemico-Biological Interactions

DOI 10.1016/s0009-2797(02)00070-4

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Abstract

Animals have evolved inducible enzymatic defenses to facilitate the biotransformation and elimination of toxic compounds encountered in the environment. The sensory component of this system consists of soluble receptors that regulate the expression of certain isoforms of cytochrome P450, other enzymes, and transporters in response to environmental chemicals. These receptors include several members of the steroid/nuclear receptor superfamily as well as the aryl hydrocarbon receptor (AHR), a member of the bHLH-PAS gene superfamily. In addition to its adaptive functions, the AHR serves poorly understood physiological roles; interference with those roles by dioxins and related chemicals causes toxicity. One approach to understanding the physiological significance of the AHR is to characterize its structure, function, and regulation in diverse species, including mammals, birds, fish, and invertebrates. These animal groups include model species with unique features that can be exploited to broaden our understanding of AHR function. Studies carried out in diverse species also provide phylogenetic information that allows inferences about the evolutionary history of the AHR. This review summarizes the current understanding of AHR diversity among animal species and the evolution of the AHR signaling pathway, as inferred from molecular studies in vertebrate and invertebrate animals. The AHR gene has undergone duplication and diversification in vertebrate animals, resulting in at least three members of an AHR gene family: AHR1, AHR2, and AHR repressor. The inability of invertebrate AHR homologs to bind dioxins and related chemicals, along with other evidence, suggests that the adaptive role of the AHR as a regulator of xenobiotic metabolizing enzymes may have been a vertebrate innovation. The physiological functions of the AHR during development appear to be ancestral to the adaptive functions. Sensitivity to the developmental toxicity of dioxins and related chemicals may have had its origin in the evolution of dioxin-binding capacity of the AHR in the vertebrate lineage.

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Differences in receptor size, affinity, sensitivity, and stability have been used to support the idea that the AHR is an evolutionarily malleable molecule that adapts to different chemical environments.
“These differences in receptor size, affinity, sensitivity, and stability have been used to support the idea that the AHR is an evolutionarily malleable molecule that adapts to different chemical environments (M. S. Denison & Nagy, 2003; M. E. Hahn, 2002; Mark E. Hahn et al., 2017).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as M. E. Hahn, 2002
The PAS gene family has undergone expansion in vertebrates, with two or three paralogs for each gene found in D. melanogaster, C. elegans, and C. intestinalis.
“The PAS gene family has undergone expansion in vertebrates, with two or three paralogs for each of the genes found in the genomes of D. melanogaster, C. elegans, and C. intestinalis (Hahn, 2002;Hahn et al., 2006).”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Hahn, 2002

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Toxicity and bioaccumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin in long-term tests with the freshwater benthic invertebratesChironomus tentansandLumbriculus variegatus
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cDNA Cloning and Characterization of a High Affinity Aryl Hydrocarbon Receptor in a Cetacean, the Beluga, Delphinapterus leucas
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Aryl Hydrocarbon Receptor is Required for Prevention of Blood Clotting and for the Development of Vasculature and Bone in the Embryos of Medaka Fish, Oryzias latipes
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An uncommon phenotype of poor inducibility of CYP1A1 in human lung is not ascribable to polymorphisms in the AHR, ARNT, or CYP1A1 genes
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Towards molecular understanding of species differences in dioxin sensitivity: initial characterization of Ah receptor cDNAs in birds and an amphibian
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cDNA cloning of an aryl hydrocarbon receptor from Baikal seals (Phoca sibirica)
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“These differences in receptor size, affinity, sensitivity to xenobiotics, and stability have been used to support the idea that the AHR is an evolutionarily malleable molecule that adapts to chemistries in changing physiological environments (Hahn 2002; Denison and Nagy 2003; Hahn et al. 2017).”
Background

Authors: Hahn, M. E.
Affiliations: Woods Hole Oceanographic Institution (US)
Corresponding author: Hahn, Mark E
ORCID: Hahn, Mark E
Venue: Chemico-Biological Interactions
Publisher: Elsevier BV
Published: 2002-09
Volume: 141
Issue: 1-2
Pages: 131-160
ISSN: 0009-2797 (ISSN-L)
DOI: 10.1016/s0009-2797(02)00070-4
OpenAlex: W1968906511
Cited by: 642
References: 204
Citations by year: 2026: 12 · 2025: 21 · 2024: 10 · 2023: 21 · 2022: 14 · 2021: 27 · 2020: 26 · 2019: 15 · 2018: 25 · 2017: 25 · 2016: 32 · 2015: 26 · 2014: 31 · 2013: 33 · 2012: 25
FWCI: 19.20
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Chemico-Biological Interactions (publishedVersion)
PubMed (publishedVersion)
Funders: Woods Hole Oceanographic Institution
National Institutes of Health
National Institute of Environmental Health Sciences (ES06272, R01ES006272)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
Keywords: aryl hydrocarbon receptor, AHR2, xenobiotic metabolism, cytochrome P450 induction, gene duplication, developmental toxicity, phylogenetic analysis, vertebrate evolution
MeSH terms: Animals, Humans, Phylogeny, Species Specificity, Receptors, Aryl Hydrocarbon, Evolution, Molecular

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Aryl hydrocarbon receptors: diversity and evolution

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