ECB-ART-49992
Curr Opin Toxicol
2017 Feb 01;2:58-71. doi: 10.1016/j.cotox.2017.02.003.
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Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution.
Hahn ME
,
Karchner SI
,
Merson RR
.
Abstract
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.
PubMed ID: 28286876
PMC ID: PMC5343764
Article link: Curr Opin Toxicol
Grant support: [+]
P42 ES007381 NIEHS NIH HHS , R01 ES006272 NIEHS NIH HHS , P20 GM103430 NIGMS NIH HHS , P30 ES003828 NIEHS NIH HHS , P20 RR016463 NCRR NIH HHS , P20 RR016457 NCRR NIH HHS , P20 GM103423 NIGMS NIH HHS
References [+] :
Aarnio,
Transcriptional profiling reveals differential expression of a neuropeptide-like protein and pseudogenes in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans.
2014, Pubmed
Aarnio, Transcriptional profiling reveals differential expression of a neuropeptide-like protein and pseudogenes in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans. 2014, Pubmed
Amemiya, The African coelacanth genome provides insights into tetrapod evolution. 2013, Pubmed
Andreasen, The zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor. 2002, Pubmed
Bessede, Aryl hydrocarbon receptor control of a disease tolerance defence pathway. 2014, Pubmed
Billiard, The role of the aryl hydrocarbon receptor pathway in mediating synergistic developmental toxicity of polycyclic aromatic hydrocarbons to zebrafish. 2006, Pubmed
Bock, From dioxin toxicity to putative physiologic functions of the human Ah receptor in homeostasis of stem/progenitor cells. 2017, Pubmed
Boitano, Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. 2010, Pubmed
Braasch, The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons. 2016, Pubmed
Brandstätter, Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor. 2016, Pubmed
Brown, Regulation of an insect cytochrome P450 monooxygenase gene (CYP6B1) by aryl hydrocarbon and xanthotoxin response cascades. 2005, Pubmed
Bunger, Abnormal liver development and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor. 2008, Pubmed
Burbach, Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. 1992, Pubmed
Burris, Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight. 2015, Pubmed
Butler, An aryl hydrocarbon receptor (AHR) homologue from the soft-shell clam, Mya arenaria: evidence that invertebrate AHR homologues lack 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone binding. 2001, Pubmed
Carney, Understanding dioxin developmental toxicity using the zebrafish model. 2006, Pubmed
Cañestro, Impact of gene gains, losses and duplication modes on the origin and diversification of vertebrates. 2013, Pubmed
Collins, 2,3,7,8-Tetracholorodibenzo-p-dioxin exposure disrupts granule neuron precursor maturation in the developing mouse cerebellum. 2008, Pubmed
Crews, Spineless provides a little backbone for dendritic morphogenesis. 2006, Pubmed
DeGroot, Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists. 2015, Pubmed
Dehal, The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. 2002, Pubmed
Del Pino Sans, Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin may alter LH release patterns by abolishing sex differences in GABA/glutamate cell number and modifying the transcriptome of the male anteroventral periventricular nucleus. 2016, Pubmed
Denison, Comparative studies of aryl hydrocarbon hydroxylase and the Ah receptor in nonmammalian species. 1985, Pubmed
Denison, Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. 2011, Pubmed
Dever, Aryl hydrocarbon receptor deletion in cerebellar granule neuron precursors impairs neurogenesis. 2016, Pubmed
Doering, Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds. 2014, Pubmed
Dong, Distal-less and homothorax regulate multiple targets to pattern the Drosophila antenna. 2002, Pubmed
Duncan, Control of distal antennal identity and tarsal development in Drosophila by spineless-aristapedia, a homolog of the mammalian dioxin receptor. 1998, Pubmed
Ema, cDNA cloning and structure of mouse putative Ah receptor. 1992, Pubmed
Emmons, The spineless-aristapedia and tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila. 1999, Pubmed
Esser, The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. 2015, Pubmed
Fairclough, Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta. 2013, Pubmed
Fitch, Distinguishing homologous from analogous proteins. 1970, Pubmed
Fraccalvieri, Comparative analysis of homology models of the AH receptor ligand binding domain: verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor. 2013, Pubmed
Freeburg, Subfunctionalization of Paralogous Aryl Hydrocarbon Receptors from the Frog Xenopus Laevis: Distinct Target Genes and Differential Responses to Specific Agonists in a Single Cell Type. 2017, Pubmed
Gasiewicz, The Ah receptor in stem cell cycling, regulation, and quiescence. 2014, Pubmed
Glasauer, Whole-genome duplication in teleost fishes and its evolutionary consequences. 2014, Pubmed
Goldstone, The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome. 2006, Pubmed , Echinobase
Goldstone, Cytochrome P450 1 genes in early deuterostomes (tunicates and sea urchins) and vertebrates (chicken and frog): origin and diversification of the CYP1 gene family. 2007, Pubmed , Echinobase
Goodale, AHR2 mutant reveals functional diversity of aryl hydrocarbon receptors in zebrafish. 2012, Pubmed
Gyoja, A genome-wide survey of bHLH transcription factors in the Placozoan Trichoplax adhaerens reveals the ancient repertoire of this gene family in metazoan. 2014, Pubmed
Hahn, Aryl hydrocarbon receptors: diversity and evolution. 2002, Pubmed
Hahn, Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species. 1994, Pubmed
Hahn, Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. 1997, Pubmed
Hahn, Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates: insights from comparative genomics. 2006, Pubmed
Hahn, Aryl hydrocarbon receptor function in early vertebrates: inducibility of cytochrome P450 1A in agnathan and elasmobranch fish. 1998, Pubmed
Hahn, The aryl hydrocarbon receptor: a comparative perspective. 1998, Pubmed
Hahn, Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor. 2009, Pubmed
Hankinson, The aryl hydrocarbon receptor complex. 1995, Pubmed
Harms, Evolutionary biochemistry: revealing the historical and physical causes of protein properties. 2013, Pubmed
Harms, Analyzing protein structure and function using ancestral gene reconstruction. 2010, Pubmed
Hayes, Hepatic transcriptional networks induced by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2007, Pubmed
Hays, Evidence that GABAergic neurons in the preoptic area of the rat brain are targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin during development. 2002, Pubmed
Hosoya, Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzo[a]pyrene in AhR repressor-deficient mice. 2008, Pubmed
Huang, The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans. 2004, Pubmed
Hubbard, Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. 2015, Pubmed
Incardona, Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism. 2006, Pubmed
Incardona, Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development. 2011, Pubmed
Jackson, Ah receptor-mediated suppression of liver regeneration through NC-XRE-driven p21Cip1 expression. 2014, Pubmed
Johnston, Interchromosomal communication coordinates intrinsically stochastic expression between alleles. 2014, Pubmed
Jones, Adaptive and specialised transcriptional responses to xenobiotic stress in Caenorhabditis elegans are regulated by nuclear hormone receptors. 2013, Pubmed
Jönsson, Role of AHR2 in the expression of novel cytochrome P450 1 family genes, cell cycle genes, and morphological defects in developing zebra fish exposed to 3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2007, Pubmed
Karchner, AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes. 2005, Pubmed
Karchner, Identification and functional characterization of two highly divergent aryl hydrocarbon receptors (AHR1 and AHR2) in the teleost Fundulus heteroclitus. Evidence for a novel subfamily of ligand-binding basic helix loop helix-Per-ARNT-Sim (bHLH-PAS) factors. 1999, Pubmed
Karchner, Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family: AHR repressor, AHR1, and AHR2. 2002, Pubmed
Kim, The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons. 2006, Pubmed
Kimura, AhR signaling activation disrupts migration and dendritic growth of olfactory interneurons in the developing mouse. 2016, Pubmed
Kimura, Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling. 2015, Pubmed
King, The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. 2008, Pubmed
King-Heiden, Reproductive and developmental toxicity of dioxin in fish. 2012, Pubmed
Knecht, Comparative developmental toxicity of environmentally relevant oxygenated PAHs. 2013, Pubmed
Kozu, Temporal regulation of late expression of Bar homeobox genes during Drosophila leg development by Spineless, a homolog of the mammalian dioxin receptor. 2006, Pubmed
Kudo, Characterization of the region of the aryl hydrocarbon receptor required for ligand dependency of transactivation using chimeric receptor between Drosophila and Mus musculus. 2009, Pubmed
Latchney, Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. 2013, Pubmed
Lavine, Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 2005, Pubmed
Lee, Molecular and functional characterization of a novel aryl hydrocarbon receptor isoform, AHR1β, in the chicken (Gallus gallus). 2013, Pubmed
Lee, Dioxin activation of CYP1A5 promoter/enhancer regions from two avian species, common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus): association with aryl hydrocarbon receptor 1 and 2 isoforms. 2009, Pubmed
Li, Genome-wide survey and expression analysis of the bHLH-PAS genes in the amphioxus Branchiostoma floridae reveal both conserved and diverged expression patterns between cephalochordates and vertebrates. 2014, Pubmed
Li, Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. 2011, Pubmed
Mackowiak, Mechanisms of xenobiotic receptor activation: Direct vs. indirect. 2016, Pubmed
Mathew, AHR-dependent misregulation of Wnt signaling disrupts tissue regeneration. 2009, Pubmed
McMillan, The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems. 2007, Pubmed
Mehta, Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). 2013, Pubmed
Mikkelsen, Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. 2007, Pubmed
Mimura, Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. 1999, Pubmed
Moura-Alves, AhR sensing of bacterial pigments regulates antibacterial defence. 2014, Pubmed
Muffato, Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes. 2010, Pubmed
Mulero-Navarro, New Trends in Aryl Hydrocarbon Receptor Biology. 2016, Pubmed
Nguyen, The search for endogenous activators of the aryl hydrocarbon receptor. 2008, Pubmed
Nukaya, Aryl hydrocarbon receptor nuclear translocator in hepatocytes is required for aryl hydrocarbon receptor-mediated adaptive and toxic responses in liver. 2010, Pubmed
Oka, Molecular cloning and characterization of the aryl hydrocarbon receptors and aryl hydrocarbon receptor nuclear translocators in the American alligator. 2016, Pubmed
Okey, An aryl hydrocarbon receptor odyssey to the shores of toxicology: the Deichmann Lecture, International Congress of Toxicology-XI. 2007, Pubmed
Patel, Ah receptor represses acute-phase response gene expression without binding to its cognate response element. 2009, Pubmed
Perry, Molecular logic behind the three-way stochastic choices that expand butterfly colour vision. 2016, Pubmed
Petersen, Distribution of mRNAs encoding the arylhydrocarbon receptor, arylhydrocarbon receptor nuclear translocator, and arylhydrocarbon receptor nuclear translocator-2 in the rat brain and brainstem. 2000, Pubmed
Peterson, Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. 1993, Pubmed
Poland, Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. 1976, Pubmed
Poland, 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. 1982, Pubmed
Poland, 2,3,7,8-Tetrachlorodibenzo-p-dioxin: environmental contaminant and molecular probe. 1976, Pubmed
Postlethwait, Subfunction partitioning, the teleost radiation and the annotation of the human genome. 2004, Pubmed
Powell-Coffman, Caenorhabditis elegans orthologs of the aryl hydrocarbon receptor and its heterodimerization partner the aryl hydrocarbon receptor nuclear translocator. 1998, Pubmed
Prasch, Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish. 2003, Pubmed
Puga, Ah receptor signals cross-talk with multiple developmental pathways. 2005, Pubmed
Putnam, The amphioxus genome and the evolution of the chordate karyotype. 2008, Pubmed
Qin, The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development. 2004, Pubmed
Qin, The Caenorhabditis elegans AHR-1 transcription complex controls expression of soluble guanylate cyclase genes in the URX neurons and regulates aggregation behavior. 2006, Pubmed
Quintana, Aryl hydrocarbon receptor control of adaptive immunity. 2013, Pubmed
Reitzel, Aryl hydrocarbon receptor (AHR) in the cnidarian Nematostella vectensis: comparative expression, protein interactions, and ligand binding. 2014, Pubmed
Reitzel, Light entrained rhythmic gene expression in the sea anemone Nematostella vectensis: the evolution of the animal circadian clock. 2010, Pubmed
Reitzel, Genetic variation at aryl hydrocarbon receptor (AHR) loci in populations of Atlantic killifish (Fundulus heteroclitus) inhabiting polluted and reference habitats. 2014, Pubmed
Richter, The genomic and cellular foundations of animal origins. 2013, Pubmed
Schneider, Intersection of AHR and Wnt signaling in development, health, and disease. 2014, Pubmed
Scott, AhR2-mediated, CYP1A-independent cardiovascular toxicity in zebrafish (Danio rerio) embryos exposed to retene. 2011, Pubmed
Sebé-Pedrós, Unexpected repertoire of metazoan transcription factors in the unicellular holozoan Capsaspora owczarzaki. 2011, Pubmed
Simakov, Hemichordate genomes and deuterostome origins. 2015, Pubmed , Echinobase
Simionato, Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics. 2007, Pubmed
Smith, Sensory neuron fates are distinguished by a transcriptional switch that regulates dendrite branch stabilization. 2013, Pubmed
Smith, Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. 2013, Pubmed
Smith, The sea lamprey meiotic map improves resolution of ancient vertebrate genome duplications. 2015, Pubmed
Smith, The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation. 2013, Pubmed
Sodergren, The genome of the sea urchin Strongylocentrotus purpuratus. 2006, Pubmed , Echinobase
Srivastava, The Amphimedon queenslandica genome and the evolution of animal complexity. 2010, Pubmed
Srivastava, The Trichoplax genome and the nature of placozoans. 2008, Pubmed
Stockinger, The aryl hydrocarbon receptor: multitasking in the immune system. 2014, Pubmed
Suga, The Capsaspora genome reveals a complex unicellular prehistory of animals. 2013, Pubmed
Sun, Cross-species transcriptomic analysis elucidates constitutive aryl hydrocarbon receptor activity. 2014, Pubmed
Tanos, Aryl hydrocarbon receptor regulates the cholesterol biosynthetic pathway in a dioxin response element-independent manner. 2012, Pubmed
Thanawala, Regional modulation of a stochastically expressed factor determines photoreceptor subtypes in the Drosophila retina. 2013, Pubmed
Tijet, Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries. 2006, Pubmed
Tittlemier, Naturally produced halogenated dimethyl bipyrroles bind to the aryl hydrocarbon receptor and induce cytochrome P4501A and porphyrin accumulation in chicken embryo hepatocytes. 2003, Pubmed
Torruella, Phylogenetic relationships within the Opisthokonta based on phylogenomic analyses of conserved single-copy protein domains. 2012, Pubmed
Van Tiem, AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). 2011, Pubmed
Venkatesh, Elephant shark genome provides unique insights into gnathostome evolution. 2014, Pubmed
Vetter, Biological activity and physicochemical parameters of marine halogenated natural products 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole and 2,4,6-tribromoanisole. 2005, Pubmed
Vezina, AHR signaling in prostate growth, morphogenesis, and disease. 2009, Pubmed
Vogel, Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. 2016, Pubmed
Vogel, A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family. 2009, Pubmed
Watanabe, Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins. 2004, Pubmed
Wernet, Stochastic spineless expression creates the retinal mosaic for colour vision. 2006, Pubmed
Whitlock, Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. 1990, Pubmed
Yasui, Functional characterization and evolutionary history of two aryl hydrocarbon receptor isoforms (AhR1 and AhR2) from avian species. 2007, Pubmed
Yoshioka, Molecular targets that link dioxin exposure to toxicity phenotypes. 2011, Pubmed
Zelante, Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. 2013, Pubmed
Zhang, Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans. 2013, Pubmed
Zudaire, The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers. 2008, Pubmed