Abstract
The Aryl hydrocarbon receptor is an ancient transcriptional factor originally discovered as a sensor of dioxin. In addition to its function as a receptor of environmental toxicants, it plays an important role in development. Although a significant amount of research has been carried out to understand the AHR signal transduction pathway and its involvement in species’ susceptibility to environmental toxicants, none of them to date has comprehensively studied its evolutionary origins. Studying the evolutionary origins of molecules can inform ancestral relationships of genes. The vertebrate genome has been shaped by two rounds of whole-genome duplications (WGD) at the base of vertebrate evolution approximately 600 million years ago, followed by lineage-specific gene losses, which often complicate the assignment of orthology. It is crucial to understand the evolutionary origins of this transcription factor and its partners, to distinguish orthologs from ancient non-orthologous homologs. In this study, we have investigated the evolutionary origins of proteins involved in the AHR pathway. Our results provide evidence of gene loss and duplications, crucial for understanding the functional connectivity of humans and model species. Multiple studies have shown that 2R-ohnologs (genes and proteins that have survived from the 2R-WGD) are enriched in signaling components relevant to developmental disorders and cancer. Our findings provide a link between the AHR pathway’s evolutionary trajectory and its potential mechanistic involvement in pathogenesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Avilla MN, Malecki KMC, Hahn ME, Wilson RH, Bradfield CA (2020) The Ah receptor: adaptive metabolism, ligand diversity, and the Xenokine model. Chem Res Toxicol 33:860–879. https://doi.org/10.1021/acs.chemrestox.9b00476
Barroso A, Mahler JV, Fonseca-Castro PH, Quintana FJ (2021) The aryl hydrocarbon receptor and the gut–brain axis. Cell Mol Immunol 18:259–268. https://doi.org/10.1038/s41423-020-00585-5
Beischlag TV, Morales JL, Hollingshead BD, Perdew GH (2008) The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukar Gene 18:207–250. https://doi.org/10.1615/critreveukargeneexpr.v18.i3.20
Bock KW (2018) From TCDD-mediated toxicity to searches of physiologic AHR functions. Biochem Pharmacol 155:419–424. https://doi.org/10.1016/j.bcp.2018.07.032
Braasch I, Peterson SM, Desvignes T, McCluskey BM, Batzel P, Postlethwait JH (2015) A new model army: emerging fish models to study the genomics of vertebrate Evo-Devo. J Exp Zool Part B Mol Dev Evol 324:316–341. https://doi.org/10.1002/jez.b.22589
Braasch I, Gehrke AR, Smith JJ, Kawasaki K, Manousaki T, Pasquier J, Amores A, Desvignes T, Batzel P, Catchen J, Berlin AM, Campbell MS, Barrell D, Martin KJ, Mulley JF, Ravi V, Lee AP, Nakamura T, Chalopin D, Fan S, Wcisel D, Cañestro C, Sydes J, Beaudry FEG, Sun Y, Hertel J, Beam MJ, Fasold M, Ishiyama M, Johnson J, Kehr S, Lara M, Letaw JH, Litman GW, Litman RT, Mikami M, Ota T, Saha NR, Williams L, Stadler PF, Wang H, Taylor JS, Fontenot Q, Ferrara A, Searle SMJ, Aken B, Yandell M, Schneider I, Yoder JA, Volff J-N, Meyer A, Amemiya CT, Venkatesh B, Holland PWH, Guiguen Y, Bobe J, Shubin NH, Palma FD, Alföldi J, Lindblad-Toh K, Postlethwait JH (2016) The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons. Nat Genet 48:427–437. https://doi.org/10.1038/ng.3526
Butler RA et al (2001) 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 β-naphthoflavone binding. Gene 278:223–234. https://doi.org/10.1016/s0378-1119(01)00724-7
Cai Y et al (2016) Molecular evidence for the existence of an aryl hydrocarbon receptor pathway in scallops Chlamys farreri. Comp Biochem Physiology Part B Biochem Mol Biology 196:74–84. https://doi.org/10.1016/j.cbpb.2016.02.006
Cañestro C et al (2009) Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes. Plos Genet 5:e1000496. https://doi.org/10.1371/journal.pgen.1000496
Castresana J (2000) Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17:540–552. https://doi.org/10.1093/oxfordjournals.molbev.a026334
Catchen JM, Conery JS, Postlethwait JH (2009) Automated identification of conserved synteny after whole-genome duplication. Genome Res 19:1497–1505. https://doi.org/10.1101/gr.090480.108
Chen K, Durand D, Farach-Colton M (2000) NOTUNG: a program for dating gene duplications and optimizing gene family trees. J Comput Biol 7:429–447. https://doi.org/10.1089/106652700750050871
Conant GC, Wolfe KH (2008) Turning a hobby into a job: How duplicated genes find new functions. Nat Rev Genet 9:938–950. https://doi.org/10.1038/nrg2482
Dehal P, Boore JL (2005) Two rounds of whole genome duplication in the ancestral vertebrate. Plos Biol 3:e314. https://doi.org/10.1371/journal.pbio.0030314
Duncan DM et al (1998) Control of distal antennal identity and tarsal development in Drosophila by spineless–aristapedia, a homolog of the mammalian dioxin receptor. Gene Dev 12:1290–1303
Eide M, Rydbeck H, Tørresen OK, Lille-Langøy R, Puntervoll P, Goldstone JV, Jakobsen KS, Stegeman J, Goksøyr A, Karlsen OA (2018) Independent losses of a xenobiotic receptor across teleost evolution. Sci. Rep. 8(1). https://doi.org/10.1038/s41598-018-28498-4
Emmons RB, Duncan D, Estes PA, Kiefel P, Mosher JT, Sonnenfeld M, Ward MP, Duncan I, Crews ST (1999) The spineless-aristapedia and tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila. Dev Camb Engl 126:3937–3945. https://doi.org/10.1242/dev.126.17.3937
Escriva H et al (2002) Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution. Mol Biol Evol 19:1440–1450. https://doi.org/10.1093/oxfordjournals.molbev.a004207
Evans BR, Karchner SI, Allan LL, Pollenz RS, Tanguay RL, Jenny MJ, Sherr DH, Hahn ME (2008) Repression of aryl hydrocarbon receptor (AHR) signaling by AHR repressor: role of DNA binding and competition for AHR nuclear translocator. Mol Pharmacol 73:387–398. https://doi.org/10.1124/mol.107.040204
Fried C et al (2003) Independent Hox-cluster duplications in lampreys. J Exp Zool Part B Mol Dev Evol 299B:18–25. https://doi.org/10.1002/jez.b.37
Furlong RF et al (2007) A degenerate ParaHox gene cluster in a degenerate vertebrate. Mol Biol Evol 24:2681–2686. https://doi.org/10.1093/molbev/msm194
Goh CS et al (2000) Co-evolution of proteins with their interaction partners edited by B. Honig. J Mol Biol 299:283–293. https://doi.org/10.1006/jmbi.2000.3732
Gu YZ, Hogenesch JB, Bradfield CA (2000) The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol 40:519–561. https://doi.org/10.1146/annurev.pharmtox.40.1.519
Gutiérrez-Vázquez C, Quintana FJ (2018) Regulation of the immune response by the aryl hydrocarbon receptor. Immunity 48:19–33. https://doi.org/10.1016/j.immuni.2017.12.012
Hahn ME (1998) The aryl hydrocarbon receptor: a comparative perspective. Comp Biochem Physiol 121(1):23–53. https://doi.org/10.1016/s0742-8413(98)10028-2
Hahn ME, Karchner SI, Evans BR, Franks DG, Merson RR, Lapseritis JM (2006) Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates: insights from comparative genomics. J Exp Zool Part Comp Exp Biology 305A:693–706. https://doi.org/10.1002/jez.a.323
Hahn ME, Allan LL, Sherr DH (2009) Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor. Biochem Pharmacol 77:485–497. https://doi.org/10.1016/j.bcp.2008.09.016
Hahn ME, Karchner SI, Merson RR (2017) Diversity as opportunity: insights from 600 million years of AHR evolution. Curr Opin Toxicol 2:58–71. https://doi.org/10.1016/j.cotox.2017.02.003
Hokamp K, McLysaght A, Wolfe KH (2003) The 2R hypothesis and the human genome sequence. J Struct Funct Genom 3:95–110. https://doi.org/10.1023/a:1022661917301
Huang X et al (2004) 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. Development 131:819–828. https://doi.org/10.1242/dev.00959
Huerta-Cepas J, Serra F, Bork P (2016) ETE 3: reconstruction, analysis, and visualization of phylogenomic data. Mol Biol Evol 33:1635–1638. https://doi.org/10.1093/molbev/msw046
Huminiecki L, Heldin CH (2010) 2R and remodeling of vertebrate signal transduction engine. Bmc Biol 8:146–146. https://doi.org/10.1186/1741-7007-8-146
Iyer M, Reschly EJ, & Krasowski MD (2006) Functional evolution of the pregnane X receptor. Expert Opin. Drug Metab. Toxicol, 2(3):381–397. https://doi.org/10.1517/17425255.2.3.381
Karchner SI et al (2005) AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes. Biochem J 392:153–161. https://doi.org/10.1042/BJ20050713
Karchner SI et al (2006) The molecular basis for differential dioxin sensitivity in birds: role of the aryl hydrocarbon receptor. Proc Natl Acad Sci 103:6252–6257. https://doi.org/10.1073/pnas.0509950103
Kasahara M, Naruse K, Sasaki S et al (2007) The medaka draft genome and insights into vertebrate genome evolution. Nature 447:714–719. https://doi.org/10.1038/nature05846
Katoh K, Standley DM (2013) MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30:772–780. https://doi.org/10.1093/molbev/mst010
Katoh K, Misawa K, Kuma K, Miyata T (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30:3059–3066. https://doi.org/10.1093/nar/gkf436
Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A (2019) RAxML-NG: a fast, scalable, and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 35:4453–4455. https://doi.org/10.1093/bioinformatics/btz305
Kuraku S et al (2009) Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after? Mol Biol Evol 26:47–59. https://doi.org/10.1093/molbev/msn222
Lamb TD (2021) Analysis of paralogons, origin of the vertebrate karyotype, and ancient chromosomes retained in extant species. Genome Biol Evol 13:evab044. https://doi.org/10.1093/gbe/evab044
Larigot L, Juricek L, Dairou J, Coumoul X (2018) AhR signaling pathways and regulatory functions. Biochim Open 7:1–9. https://doi.org/10.1016/j.biopen.2018.05.001
Lavine JA et al (2005) Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci 88:60–72. https://doi.org/10.1093/toxsci/kfi228
Letunic I, Bork P (2021) Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab301
Leung MCK, Procter AC, Goldstone JV, Foox J, DeSalle R, Mattingly CJ, Siddall ME, Timme-Laragy AR (2017) Applying evolutionary genetics to developmental toxicology and risk assessment. Reprod Toxicol 69:174–186. https://doi.org/10.1016/j.reprotox.2017.03.003
Makino T, McLysaght A (2010) Ohnologs in the human genome are dosage balanced and frequently associated with disease. Proc Natl Acad Sci 107:9270–9274. https://doi.org/10.1073/pnas.0914697107
McIntosh BE, Hogenesch JB, Bradfield CA (2010) Mammalian Per-Arnt-sim proteins in environmental adaptation. Physiology 72:625–645. https://doi.org/10.1146/annurev-physiol-021909-135922
McLysaght A, Hokamp K, Wolfe KH (2002) Extensive genomic duplication during early chordate evolution. Nat Genet 31:200–204. https://doi.org/10.1038/ng884
Mehta TK et al (2013) Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). Proc National Acad Sci 110:16044–16049. https://doi.org/10.1073/pnas.1315760110
Meyer A, Schartl M (1999) Gene and genome duplications in vertebrates: the one-to-four (-to-eight in fish) rule and the evolution of novel gene functions. Curr Opin Cell Biol 11:699–704. https://doi.org/10.1016/s0955-0674(99)00039-3
Mottes F et al (2021) The impact of whole genome duplications on the human gene regulatory networks. Plos Comput Biol 17:e1009638. https://doi.org/10.1371/journal.pcbi.1009638
Muffato M et al (2010) Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes. Bioinformatics 26:1119–1121. https://doi.org/10.1093/bioinformatics%2Fbtq079
Nakatani Y, Takeda H, Kohara Y, Morishita S (2007) Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates. Genome Res 17:1254–1265. https://doi.org/10.1101/gr.6316407
Nakatani Y et al (2021) Reconstruction of proto-vertebrate, proto-cyclostome and proto-gnathostome genomes provides new insights into early vertebrate evolution. Nat Commun 12:4489. https://doi.org/10.1038/s41467-021-24573-z
Nebert DW (2017) Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per-Arnt-sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals. Prog Lipid Res 67:38–57. https://doi.org/10.1016/j.plipres.2017.06.001
Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated Induction of the CYP1 enzymes in environmental toxicity and cancer*. J Biol Chem 279:23847–23850. https://doi.org/10.1074/jbc.r400004200
Nelson JS, Grande TC, Wilson MV (2016) Fishes of the World. Wiley, Hoboken
Ohno S (1970) Evolution by gene duplication. Springer, Berlin, Heidelberg
Okey AB (2007) An aryl hydrocarbon receptor odyssey to the shores of toxicology: the deichmann lecture, international congress of toxicology-XI. Toxicol Sci 98:5–38. https://doi.org/10.1093/toxsci/kfm096
Panopoulou G, Poustka AJ (2005) Timing and mechanism of ancient vertebrate genome duplications—the adventure of a hypothesis. Trends Genet 21:559–567. https://doi.org/10.1016/j.tig.2005.08.004
Parichy DM (2016) The gar is a fish... is a bird... is a mammal? Nat Genet 48:344–345. https://doi.org/10.1038/ng.3532
Postlethwait J, Amores A, Cresko W, Singer A, Yan YL (2004) Subfunction partitioning, the teleost radiation and the annotation of the human genome. Trends Genet 20:481–490. https://doi.org/10.1016/j.tig.2004.08.001
Powell-Coffman JA et al (1998) Caenorhabditis elegans orthologs of the aryl hydrocarbon receptor and its heterodimerization partner the aryl hydrocarbon receptor nuclear translocator. Proc Natl Acad Sci 95:2844–2849. https://doi.org/10.1073/pnas.95.6.2844
Qin H, Powell-Coffman JA (2004) The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development. Dev Biol 270:64–75. https://doi.org/10.1016/j.ydbio.2004.02.004
Quintana FJ (2013) The aryl hydrocarbon receptor: a molecular pathway for the environmental control of the immune response. Immunology 138:183–189. https://doi.org/10.1111/imm.12046
Quintana FJ, Sherr DH (2013) Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev 65:1148–1161. https://doi.org/10.1124/pr.113.007823
Reitzel AM et al (2010) Light entrained rhythmic gene expression in the sea anemone Nematostella vectensis: the evolution of the animal circadian clock. PLoS ONE 5:e12805. https://doi.org/10.1371/journal.pone.0012805
Reitzel AM et al (2014a) Genetic variation at aryl hydrocarbon receptor (AHR) loci in populations of Atlantic killifish (Fundulus heteroclitus) inhabiting polluted and reference habitats. Bmc Evol Biol 14:6–6. https://doi.org/10.1186/1471-2148-14-6
Reitzel AM et al (2014b) Aryl hydrocarbon receptor (AHR) in the cnidarian Nematostella vectensis: comparative expression, protein interactions, and ligand binding. Dev Genes Evol 224:13–24. https://doi.org/10.1007/s00427-013-0458-4
Rothhammer V, Quintana FJ (2019) The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol 19:184–197. https://doi.org/10.1038/s41577-019-0125-8
Sacerdot C, Louis A, Bon C, Berthelot C, Crollius HR (2018) Chromosome evolution at the origin of the ancestral vertebrate genome. Genome Biol 19:166. https://doi.org/10.1186/s13059-018-1559-1
Shaffer HB, Minx P, Warren DE, Shedlock AM, Thomson RC, Valenzuela N, Abramyan J, Amemiya CT, Badenhorst D, Biggar KK, Borchert GM, Botka CW, Bowden RM, Braun EL, Bronikowski AM, Bruneau BG, Buck LT, Capel B, Castoe TA, Czerwinski M, Delehaunty KD, Edwards SV, Fronick CC, Fujita MK, Fulton L, Graves TA, Green RE, Haerty W, Hariharan R, Hernandez O, Hillier LW, Holloway AK, Janes D, Janzen FJ, Kandoth C, Kong L, de Koning AJ, Li Y, Literman R, McGaugh SE, Mork L, O’Laughlin M, Paitz RT, Pollock DD, Ponting CP, Radhakrishnan S, Raney BJ, Richman JM, John JS, Schwartz T, Sethuraman A, Spinks PQ, Storey KB, Thane N, Vinar T, Zimmerman LM, Warren WC, Mardis ER, Wilson RK (2013) The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage. Genome Biol 14:R28. https://doi.org/10.1186/gb-2013-14-3-r28
Shankar P et al (2020) A review of the functional roles of the zebrafish aryl hydrocarbon receptors. Toxicol Sci 178:215–238. https://doi.org/10.1093/toxsci/kfaa143
Shen W, Ren H (2021) TaxonKit: a practical and efficient NCBI taxonomy toolkit. J Genet Gen. https://doi.org/10.1016/j.jgg.2021.03.006
Sidow A (1996) Gen(om)e duplications in the evolution of early vertebrates. Curr Opin Genet Dev 6:715–722. https://doi.org/10.1016/s0959-437x(96)80026-8
Simakov O et al (2020) Deeply conserved synteny resolves early events in vertebrate evolution. Nat Ecol Evol 4:820–830. https://doi.org/10.1038/s41559-020-1156-z
Singh PP, Isambert H (2020) OHNOLOGS v2: a comprehensive resource for the genes retained from whole genome duplication in vertebrates. Nucleic Acids Res 48:D724–D730. https://doi.org/10.1093/nar/gkz909
Singh PP et al (2012) On the expansion of “dangerous” gene repertoires by whole-genome duplications in early vertebrates. Cell Rep 2:1387–1398. https://doi.org/10.1016/j.celrep.2012.09.034
Singh PP et al (2015) Identification of ohnolog genes originating from whole genome duplication in early vertebrates, based on synteny comparison across multiple genomes. Plos Comput Biol 11:e1004394. https://doi.org/10.1371/journal.pcbi.1004394
Smith JJ et al (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet 45:415–421. https://doi.org/10.1038/ng.2568
Smith JJ et al (2018) The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution. Nat Genet 50:270–277. https://doi.org/10.1038/s41588-017-0036-1
Sonnenfeld M, Ward M, Nystrom G, Mosher J, Stahl S, Crews S (1997) The Drosophila tango gene encodes a bHLH-PAS protein that is orthologous to mammalian Arnt and controls CNS midline and tracheal development. Development 124:4571–4582. https://doi.org/10.1242/dev.124.22.4571
Stadler PF et al (2004) Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii. Mol Phylogenet Evol 32:686–694. https://doi.org/10.1016/j.ympev.2004.03.015
Stolzer M, Lai H, Xu M, Sathaye D, Vernot B, Durand D (2012) Inferring duplications, losses, transfers, and incomplete lineage sorting with nonbinary species trees. Bioinformatics 28:i409–i415. https://doi.org/10.1093/bioinformatics/bts386
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, von Mering C (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47:D607–D613. https://doi.org/10.1093/nar/gky1131
Szklarczyk D et al (2021) The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 49(18):10800. https://doi.org/10.1093/nar/gkaa1074
Szöllősi GJ, Tannier E, Daubin V, Boussau B (2015) The inference of gene trees with species trees. Systematic Biol 64:e42–e62. https://doi.org/10.1093/sysbio/syu048
Taylor JS, Braasch I, Frickey T, Meyer A, de Peer YV (2003) Genome duplication, a trait shared by 22,000 species of ray-finned fish. Genome Res 13:382–390. https://doi.org/10.1101/gr.640303
Tinti M et al (2014) Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers. Open Biol 4:140029. https://doi.org/10.1098/rsob.140029
Whitlock JP (1999) Induction of cytochrome P4501A1. Annu Rev Pharmacol 39:103–125. https://doi.org/10.1146/annurev.pharmtox.39.1.103
Wittbrodt J, Meyer A, Schartl M (1998) More genes in fish? BioEssays 20:511–515. https://doi.org/10.1002/(sici)1521-1878(199806)20:6%3C511::aid-bies10%3E3.0.co;2-3
Xu X et al (2021) Species-specific differences in aryl hydrocarbon receptor responses: how and why? Int J Mol Sci 22(24):13293. https://doi.org/10.3390/ijms222413293
Yasui T et al (2007) Functional characterization and evolutionary history of two aryl hydrocarbon receptor isoforms (AhR1 and AhR2) from Avian species. Toxicol Sci 99:101–117. https://doi.org/10.1093/toxsci/kfm139
Acknowledgements
We would like to thank anonymous Reviewers for their insightful suggestions.
Funding
This research was supported by The National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs) CRACK IT project DARTpaths [project number CRACKITDP-P1-2]. Computational work was performed in the VSC (Flemish Supercomputer Center), funded by the Research Foundation—Flanders (FWO) and the Flemish Government.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Handling editor: David Alvarez-Ponce.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Bhalla, D., van Noort, V. Molecular Evolution of Aryl Hydrocarbon Receptor Signaling Pathway Genes. J Mol Evol 91, 628–646 (2023). https://doi.org/10.1007/s00239-023-10124-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-023-10124-1