Diversity as opportunity: Insights from 600 million years of AHR evolution

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.

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

“…There is a general consensus that the AhR of modern humans is implicated in DNA repair (Dittmann et al, ; Schreck et al, ), tumor suppression (Fan et al, ; Yu et al, ), epidermal barrier function (Noakes, ), skin tanning response, and melanocyte homeostasis (Jux et al, ; Luecke et al, ). Phylogenetic analysis suggested that the ability of vertebrate AhR to sense xenobiotics was acquired at a late stage of evolution, implying that the driving force for evolutionary conservation of AhR lies not only in its role in xenobiotic metabolism but also in normal cell development (Hahn et al, ; Hao & Whitelaw, ).…”

“…There is a general consensus that the AhR of modern humans is implicated in DNA repair (Dittmann et al, 2016;Schreck et al, 2009), tumor suppression (Fan et al, 2010;Yu et al, 2017), epidermal barrier function (Noakes, 2015), skin tanning response, and melanocyte homeostasis (Jux et al, 2011;Luecke et al, 2010). Phylogenetic analysis suggested that the ability of vertebrate AhR to sense xenobiotics was acquired at a late stage of evolution, implying that the driving force for evolutionary conservation of AhR lies not only in its role in xenobiotic metabolism but also in normal cell development (Hahn et al, 2017;Hao & Whitelaw, 2013). Hubbard et al (2016) showed that the AhR variant in modern humans contains Val381 residue in the ligandbinding domain, while the AhR of Neanderthals, and a Denisovan individual, as well as nonhuman primates and other vertebrates (rodents) encode the ancestral Ala381 variant.…”

When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations

“…A major difference is in the number of AHR genes. In contrast to the single AHR gene present in most mammals, fish (and most other vertebrates) have multiple AHR genes (Hahn, Karchner, & Merson, 2017;Hahn et al, 2006). Fish typically have four AHR genes, products of a tandem gene duplication (AHR1 and AHR2) and paralogs of each of these (designated "a" and "b"), the result of a whole-genome duplication at the base of the teleost lineage, after its divergence from the lineage leading to tetrapods (Goodale et al, 2012;Incardona et al, 2006).…”

The growth and infectivity of Leishmania major is not altered by in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

“…Although AhR proteins have been identified in numerous organisms within the kingdom Animalia (but not outside it), the ability to bind planar aromatic hydrocarbons with high affinity appears to be unique to vertebrates [15]. Leishmania organisms are eukaryotes, but as trypanosomes they are classified outside the kingdom Animalia, and an AhR has not been reported to exist within them.…”