The DOI matches its Crossref record; 203 of the 203 references it cites were found in a registry or an index.
Aryl hydrocarbon receptors: diversity and evolution
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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“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
In the citing paper
“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
Citations
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Self-citationIntrinsic Function of the Aryl Hydrocarbon (Dioxin) Receptor as a Key Factor in Female Reproduction
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Self-citationGene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor
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Rodent Genetic Models of Ah Receptor Signaling
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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
Metadata
- 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)
- OpenAlex
- W1968906511
- Cited by
- 642
- References
- 203
- 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
- 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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