Development Genes and Evolution

, Volume 218, Issue 11–12, pp 579–590 | Cite as

Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae

  • Naohito Takatori
  • Thomas Butts
  • Simona Candiani
  • Mario Pestarino
  • David E. K. Ferrier
  • Hidetoshi Saiga
  • Peter W. H. Holland
Original Article

Abstract

The homeobox genes comprise a large and diverse gene superfamily, many of which encode transcription factors with pivotal roles in the embryonic development of animals. We searched the assembled draft genome sequence of an amphioxus, Branchiostoma floridae, for genes possessing homeobox sequences. Phylogenetic analysis was used to divide these into gene families and classes. The 133 amphioxus homeobox genes comprise 60 ANTP class genes, 29 PRD genes (excluding Pon and Pax1/9), nine TALE genes, seven POU genes, seven LIM genes, five ZF genes, four CUT genes, four HNF genes, three SINE genes, one CERS gene, one PROS gene, and three unclassified genes. Ten of the 11 homeobox gene classes are less diverse in amphioxus than humans, as a result of gene duplication on the vertebrate lineage. Amphioxus possesses at least one member for all of the 96 homeobox gene families inferred to be present in the common ancestor of chordates, including representatives of the Msxlx, Bari, Abox, Nk7, Ro, and Repo gene families that have been lost from tunicates and vertebrates. We find duplication of several homeobox genes in the cephalochordate lineage (Mnx, Evx, Emx, Vent, Nk1, Nedx, Uncx, Lhx2/9, Hmbox, Pou3, and Irx) and several divergent genes that probably originated by extensive sequence divergence (Hx, Ankx, Lcx, Acut, Atale, Azfh, Ahbx, Muxa, Muxb, Aprd1–6, and Ahnf). The analysis reveals not only the repertoire of amphioxus homeobox genes but also gives insight into the evolution of chordate homeobox genes.

Keywords

Homeodomain Lancelet Molecular evolution Molecular phylogeny Chordate 

Supplementary material

427_2008_245_MOESM1_ESM.pdf (164 kb)
Supplementary Fig. 1Arbitrarily rooted phylogenetic tree of ANTP class genes generated by maximum likelihood based on homeodomain sequences. Gene family support nodes are shown, except in cases where these are not recovered as monophyletic (Hox families, NK2, NK4, and Vent) due to uneven rates of sequence evolution and complex histories. The two Vent genes are represented by a single branch, since they have identical homeodomains. Amphioxus homeodomains identified in this study are marked with closed circles. The two B. floridae ro alleles differ in predicted amino acid sequence; Protein ID 290436 was used. Scale bar indicates evolutionary distance of 0.5 amino acid substitutions per position. The following notes apply to all supplementary figures: numbers at nodes indicate bootstrap support values given as a percentage of 500 bootstrap pseudoreplications of the data. Names on branches indicate protein names, with species name in abbreviated form and accession ID. Species codes are: Bb Branchiostoma belcheri; Bf Branchiostoma floridae; Ce Caenorhabditis elegans; Cf Canis familiaris; Ci Ciona intestinalis; Dm Drosophila melanogaster; Dr Danio rerio; Gg Gallus gallus; He Heliocidaris erythrogramma; Hr Halocynthia roretzi; Hs Homo sapiens; Mm Mus musculus; Nv Nematostella vectensis; Od Oikopleura dioica; Pd Platynereis dumerilii; Sk Saccoglossus kowalevskii; Sp Strongylocentrotus purpuratus;; Tf Takifugu rubripes; and Xl Xenopus laevis. (PDF 168 KB)
427_2008_245_Fig2_ESM.gif (107 kb)
Supplementary Fig. 2

Arbitrarily rooted phylogenetic tree of Pax genes generated by maximum likelihood based on paired domain sequences. Scale bar indicates evolutionary distance of 0.05 amino acid substitutions per position. In this and all subsequent supplementary figures, amphioxus proteins identified in this study are represented without an accession ID and are marked with closed circles; amphioxus sequences previously reported are represented with accession ID and marked with open circles. The B. floridae genome Pax6 sequence used corresponds to Protein ID 291575. (GIF 109 KB)

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High resolution image file (TIFF 28 MB)
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Supplementary Fig. 3

Arbitrarily rooted phylogenetic tree of PRD class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 193 KB)

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High resolution image file (TIFF 32 MB)
427_2008_245_Fig4_ESM.gif (120 kb)
Supplementary Fig. 4

Arbitrarily rooted phylogenetic tree of LIM class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 122 KB)

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High resolution image file (TIFF 31 MB)
427_2008_245_Fig5_ESM.gif (71 kb)
Supplementary Fig. 5

Arbitrarily rooted phylogenetic tree of POU class genes generated by maximum likelihood based on homeodomain sequences. The highly divergent Hdx gene is not included. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 73 KB)

427_2008_245_Fig5_ESM.tif (28.9 mb)
High resolution image file (TIFF 30 MB)
427_2008_245_Fig6_ESM.gif (57 kb)
Supplementary Fig. 6

Arbitrarily rooted phylogenetic tree of HNF class genes generated by maximum likelihood based on homeodomain sequences. The highly divergent Ahnf gene is not included. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 58 KB)

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High resolution image file (TIFF 26 MB)
427_2008_245_Fig7_ESM.gif (58 kb)
Supplementary Fig. 7

Arbitrarily rooted phylogenetic tree of SINE class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.05 amino acid substitutions per position. (GIF 59 KB)

427_2008_245_Fig7_ESM.tif (26.8 mb)
High resolution image file (TIFF 28 MB)
427_2008_245_Fig8_ESM.gif (101 kb)
Supplementary Fig. 8

Arbitrarily rooted phylogenetic tree of TALE class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 103 KB)

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High resolution image file (TIFF 31 MB)
427_2008_245_Fig9_ESM.gif (27 kb)
Supplementary Fig. 9

Arbitrarily rooted phylogenetic tree of PROS class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 28 KB)

427_2008_245_Fig9_ESM.tif (19.6 mb)
High resolution image file (TIFF 20 MB)
427_2008_245_Fig10_ESM.gif (152 kb)
Supplementary Fig. 10

Arbitrarily rooted phylogenetic tree of homeodomains from ZF class genes generated by the maximum likelihood. Multiple homeodomains from a single gene are numbered according to their position from the N terminus. Scale bar indicates evolutionary distance of 0.2 amino acid substitutions per position. (GIF 156 KB)

427_2008_245_Fig10_ESM.tif (32.3 mb)
High resolution image file (TIFF 33 MB)
427_2008_245_Fig11_ESM.gif (62 kb)
Supplementary Fig. 11

Arbitrarily rooted phylogenetic tree of CERS class genes generated by maximum likelihood based on homeodomain sequences. Scale bar indicates evolutionary distance of 0.1 amino acid substitutions per position. (GIF 63 KB)

427_2008_245_Fig11_ESM.tif (22.2 mb)
High resolution image file (TIFF 23 MB)
427_2008_245_MOESM12_ESM.doc (38 kb)
Supplementary Table 1Chromosomal location and putative synteny of putative human homologues of amphioxus genes neighboring Pou3L. (DOC 38 KB)

References

  1. Abascal F, Zardoya R, Posada D (2005) ProtTest: selection of best-fit models of protein evolution. Bioinformatics 21:2104–2105PubMedCrossRefGoogle Scholar
  2. Booth HAF, Holland PWH (2004) Eleven daughters of NANOG. Genomics 84:229–238PubMedCrossRefGoogle Scholar
  3. Booth HAF, Holland PWH (2007) Annotation, nomenclature and evolution of four novel homeobox genes expressed in the human germ line. Gene 387:7–14PubMedCrossRefGoogle Scholar
  4. Bourlat SJ, Juliusdottir T, Lowe CJ, Freeman R, Aronowicz J, Kirschner M, Lander ES, Thorndyke M, Nakano H, Kohn AB et al (2006) Deuterostome phylogeny reveals monophyletic chordates and the new phylum Xenoturbellida. Nature 444:85–88PubMedCrossRefGoogle Scholar
  5. Brooke NM, Garcia-Fernàndez J, Holland PWH (1998) The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature 392:920–922PubMedCrossRefGoogle Scholar
  6. Bürglin TR (1994) A comprehensive classification of homeobox genes. In: Duboue D (ed) Guidebook to the homeobox genes. Oxford University Press, Oxford, pp 25–71Google Scholar
  7. Bürglin TR (1995) The evolution of homeobox genes. In: Arai R, Kato M, Doi Y (eds) Biodiversity and evolution. The National Science Museum Foundation, Tokyo, pp 291–336Google Scholar
  8. Bürglin TR (1997) Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals. Nucleic Acids Res 25:4173–4180PubMedCrossRefGoogle Scholar
  9. Bürglin TR (1998) The PBC domain contains a MEINOX domain: coevolution of Hox and TALE homeobox genes. Dev Genes Evol 208:113–116PubMedCrossRefGoogle Scholar
  10. Bürglin TR, Cassata G (2002) Loss and gain of domains during evolution of cut superclass homeobox genes. Int J Dev Biol 46:115–123PubMedGoogle Scholar
  11. Butts T, Holland PWH, Ferrier DEK (2008) The Urbilaterian Super-Hox cluster. Trends in Genetics 24:259–262PubMedCrossRefGoogle Scholar
  12. Candiani S, Castagnola P, Oliveri D, Pestarino M (2002) Cloning and developmental expression of AmphiBrn1/2/4, a POU III gene in amphioxus. Mech Dev 116:231–234PubMedCrossRefGoogle Scholar
  13. Candiani S, Oliveri D, Parodi M, Bertini E, Pestarino M (2006) Expression of AmphiPOU-IV in the developing neural tube and epidermal sensory neural precursors in amphioxus supports a conserved role of class IV POU genes in the sensory cells development. Dev Genes Evol 216:623–633PubMedCrossRefGoogle Scholar
  14. Candiani S, Holland ND, Oliveri D, Parodi M, Pestarino M (2008) Expression of the amphioxus Pit-1 gene (AmphiPOU1F1/Pit-1) exclusively in the developing preoral organ, a putative homolog of the vertebrate adenohypophysis. Brain Res Bull 75:324–330PubMedCrossRefGoogle Scholar
  15. Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE (2002) Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol Cell 10:1129–1137PubMedCrossRefGoogle Scholar
  16. Chu-Lagraff Q, Wright DM, McNeil LK, Doe CQ (1991) The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila. Development Suppl 2:79–85Google Scholar
  17. Dehal P, Boore JL (2005) Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol 3:e314PubMedCrossRefGoogle Scholar
  18. Delsuc F, Brinkmann H, Chourrout D, Philippe H (2006) Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature 439:965–968PubMedCrossRefGoogle Scholar
  19. Dildrop R, Ruther U (2004) Organization of Iroquois genes in fish. Dev Genes Evol 214:267–276PubMedCrossRefGoogle Scholar
  20. Doe CQ, Chu-LaGraff Q, Wright DM, Scott MP (1991) The prospero gene specifies cell fates in the Drosophila central nervous system. Cell 65:451–464PubMedCrossRefGoogle Scholar
  21. Dozier C, Kagoshima H, Niklaus G, Cassata G, Bürglin TR (2001) The Caenorhabditis elegans Six/sine oculis class homeobox gene ceh-32 is required for head morphogenesis. Dev Biol 236:289–303PubMedCrossRefGoogle Scholar
  22. Felsenstein J (1993) PHYLIP (Phylogeny Inference Package) version 3.5c. Department of Genetics, University of Washington, SeattleGoogle Scholar
  23. Ferrier DEK, Minguillon C, Holland PWH, Garcia-Fernàndez J (2000) The amphioxus Hox cluster: deuterostome posterior flexibility and Hox14. Evolution and Development 2:284–293PubMedCrossRefGoogle Scholar
  24. Galliot B, de Vargas C, Miller D (1999) Evolution of homeobox genes: Q50 Paired-like genes founded the Paired class. Dev Genes Evol 209:186–197PubMedCrossRefGoogle Scholar
  25. Garcia-Fernàndez J, Holland PWH (1994) Archetypal organization of the amphioxus Hox gene cluster. Nature 370:563–566PubMedCrossRefGoogle Scholar
  26. Glardon S, Holland LZ, Gehring WJ, Holland ND (1998) Isolation and developmental expression of the amphioxus Pax-6 gene (AmphiPax-6): insights into eye and photoreceptor evolution. Development 125:2701–2710PubMedGoogle Scholar
  27. Gomez-Skarmeta JL, Modolell J (2002) Iroquois genes: genomic organization and function in vertebrate neural development. Curr Opin Genet Dev 12:403–408PubMedCrossRefGoogle Scholar
  28. Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704PubMedCrossRefGoogle Scholar
  29. Guindon S, Lethiec F, Duroux P, Gascuel O (2005) PHYML Online—a web server for fast maximum likelihood-based phylogenetic inference. Nucleic Acids Res 33:W557–W559PubMedCrossRefGoogle Scholar
  30. Hobert O, Westphal H (2000) Functions of LIM-homeobox genes. Trends Genet 16:75–83PubMedCrossRefGoogle Scholar
  31. Holland PWH, Garcia-Fernàndez J, Williams NA, Sidow A (1994) Gene duplications and the origins of vertebrate development. Development 1994 (Suppl):125–133Google Scholar
  32. Holland ND, Holland LZ, Kozmik Z (1995) An amphioxus Pax gene, AmphiPax-1, expressed in embryonic endoderm, but not in mesoderm: implications for the evolution of class I paired box genes. Mol Mar Biol Biotechnol 4:206–214PubMedGoogle Scholar
  33. Holland LZ, Schubert M, Kozmik Z, Holland ND (1999) AmphiPax-3/7, an amphioxus paired box gene: insights into chordate myogenesis, neurogenesis, and the possible evolutionary precursor of definitive vertebrate neural crest. Evol Dev 1:153–165PubMedCrossRefGoogle Scholar
  34. Holland PWH, Booth HAF, Bruford EA (2007) Classification and nomenclature of all human homeobox genes. BMC Biol 5:47PubMedCrossRefGoogle Scholar
  35. Holland LZ, Albalat R, Azumi K, Benito-Gutiérrez È, Blow MJ, Bronner-Fraser M, Brunet F, Butts T, Candiani S, Dishaw LJ, Ferrier DEK, Garcia-Fernàndez J, Gibson-Brown JJ, Gissi C, Godzik A, Hallböök F, Hirose D, Hosomichi K, Ikuta T, Inoko H, Kasahara M, Kasamatsu J, Kawashima T, Kimura A, Kobayashi M, Kozmik Z, Kubokawa K, Laudet V, Litman GW, McHardy AC, Meulemans D, Nonaka M, Olinski RP, Pancer Z, Pennacchio LA, Pestarino M, Rast JP, Rigoutsos I, Robinson-Rechavi M, Roch G, Saiga H, Sasakura Y, Satake M, Satou Y, Schubert M, Sherwood N, Shiina T, Takatori N, Tello J, Vopalensky P, Wada S, Xu A, Ye Y, Yoshida K, Yoshizaki F, Yu J-K, Zhang Q, Zmasek CM, Putnam NH, Rokhsar DS, Satoh N, Holland PWH (2008) The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res 18:1100–1111PubMedCrossRefGoogle Scholar
  36. Howard-Ashby M, Materna SC, Brown CT, Chen L, Cameron RA, Davidson EH (2006) Identification and characterisation of homeobox transcription factor genes in Strongylocentrotus purpuratus, and their expression in embryonic development. Dev Biol 300:74–89PubMedCrossRefGoogle Scholar
  37. Irimia M, Maeso I, Garcia-Fernandez J (2008) Convergent evolution of clustering of Iroquois homeobox genes across metazoans. Mol Biol Evol 25:1521–1525PubMedCrossRefGoogle Scholar
  38. Jackman WR, Langeland JA, Kimmel CB (2000) Islet reveals segmentation in the amphioxus hindbrain homolog. Dev Biol 220:16–26PubMedCrossRefGoogle Scholar
  39. Kozmik Z, Holland ND, Kalousova A, Paces J, Schubert M, Holland LZ (1999) Characterization of an amphioxus paired box gene, AmphiPax2/5/8: developmental expression patterns in optic support cells, nephridium, thyroid-like structures and pharyngeal gill slits, but not in the midbrain-hindbrain boundary region. Development 126:1295–304PubMedGoogle Scholar
  40. Kumar S, Tamura K, Nei M (2004) MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163PubMedCrossRefGoogle Scholar
  41. Letunic I, Copley RR, Pils B, Pinkert S, Schultz J, Bork P (2006) SMART 5: domains in the context of genomes and networks. Nucleic Acids Res 34:D257–D260PubMedCrossRefGoogle Scholar
  42. Liu M, Su M, Lyons GE, Bodmer R (2006) Functional conservation of zinc-finger homeodomain gene zfh1/SIP1 in Drosophila heart development. Dev Genes Evol 216:683–693PubMedCrossRefGoogle Scholar
  43. Luke GN, Castro LFC, McLay K, Bird C, Coulson A, Holland PWH (2003) Dispersal of NK homeobox gene clusters in amphioxus and humans. Proc Natl Acad Sci USA 100:5292–5295PubMedCrossRefGoogle Scholar
  44. Mesika A, Ben-Dor S, Laviad EL, Futerman AH (2007) A new functional motif in Hox domain-containing ceramide synthases: identification of a novel region flanking the Hox and TLC domains essential for activity. J Biol Chem 282:27366–27373PubMedCrossRefGoogle Scholar
  45. Minguillón C, Ferrier DEK, Cebrián C, Garcia-Fernàndez J (2002) Gene duplications in the prototypical cephalochordate amphioxus. Gene 287:121–128PubMedCrossRefGoogle Scholar
  46. Mizutani Y, Kihara A, Igarashi Y (2005) Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 390:263–271PubMedCrossRefGoogle Scholar
  47. Mukherjee K, Bürglin TR (2007) Comprehensive analysis of animal TALE homeobox genes: new conserved motifs and cases of accelerated evolution. J Mol Evol 65:137–153PubMedCrossRefGoogle Scholar
  48. Nishijima I, Ohtoshi A (2006) Characterization of a novel prospero-related homeobox gene, Prox2. Mol Genet Genom 275:471–478CrossRefGoogle Scholar
  49. Ohshima K, Hattori M, Yada T, Gojobori T, Sakaki Y, Okada N (2003) Whole-genome screening indicates a possible burst of formation of processed pseudogenes and Alu repeats by particular L1 subfamilies in ancestral primates. Genome Biol 4:R74PubMedCrossRefGoogle Scholar
  50. Peters T, Dildrop R, Ausmeier K, Ruther U (2000) Organization of mouse Iroquois homeobox genes in two clusters suggests a conserved regulation and function in vertebrate development. Genome Res 10:1453–1462PubMedCrossRefGoogle Scholar
  51. Pewzner-Jung Y, Ben-Dor S, Futerman AH (2006) When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: insights into the regulation of ceramide synthesis. J Biol Chem 281:25001–25005PubMedCrossRefGoogle Scholar
  52. Putnam NH, Butts T, Ferrier DEK, Furlong RF, Hellsten U, Kawashima T, Robinson-Rechavi M, Shoguchi E, Terry A, Yu J-K, Benito-Gutiérrez E, Dubchak I, Garcia-Fernàndez J, Grigoriev IV, Horton AC, de Jong PJ, Jurka J, Kapitonov V, Kohara Y, Kuroki Y, Lindquist E, Lucas S, Kazutoyo O, Pennacchio LA, Salamov AA, Satou Y, Sauka-Spengler T, Schmutz J, Shin I-T, Toyoda A, Gibson-Brown JJ, Bronner-Fraser M, Fujiyama A, Holland LZ, Holland PWH, Satoh N, Rokhsar DS (2008) The amphioxus genome and the evolution of the chordate karyotype. Nature 453:1064–1071PubMedCrossRefGoogle Scholar
  53. Ryan JF, Burton PM, Mazza ME, Kwong GK, Mullikin JC, Finnerty JF (2006) The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis. Genome Biol 7:R64PubMedCrossRefGoogle Scholar
  54. Schultz J, Milpetz F, Bork P, Ponting CP (1998) SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci USA 95:5857–5864PubMedCrossRefGoogle Scholar
  55. Seo HC, Curtiss J, Mlodzik M, Fjose A (1999) Six class homeobox genes in Drosophila belong to three distinct families and are involved in head development. Mech Dev 83:127–139PubMedCrossRefGoogle Scholar
  56. Takatori N, Saiga H (2008) Evolution of CUT class homeobox genes in the lineage to the vertebrates: insights from the analysis of the genomic sequence of amphioxus, Branchiostoma floridae. Int J Dev Biol 52(7) (in press). doi:10.1387/ijdb.072541nt
  57. Wada S, Tokuoka M, Shoguchi E, Kobayashi K, Di Gregorio A, Spagnuolo A, Branno M, Kohara Y, Rokhsar D, Levine M et al (2003) A genomewide survey of developmentally relevant genes in Ciona intestinalis. II. Genes for homeobox transcription factors. Dev Genes Evol 213:222–234PubMedCrossRefGoogle Scholar
  58. Yousef MS, Matthews BW (2005) Structural basis of Prospero-DNA interaction: implications for transcription regulation in developing cells. Structure 13:601–607PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Naohito Takatori
    • 1
    • 4
  • Thomas Butts
    • 2
  • Simona Candiani
    • 3
  • Mario Pestarino
    • 3
  • David E. K. Ferrier
    • 2
    • 5
  • Hidetoshi Saiga
    • 1
  • Peter W. H. Holland
    • 2
  1. 1.Department of Biological Sciences, Graduate School of Science and EngineeringTokyo Metropolitan UniversityHachiohjiJapan
  2. 2.Department of ZoologyUniversity of OxfordOxfordUK
  3. 3.Dipartimento di BiologiaUniversità di GenovaGenoaItaly
  4. 4.Department of Biological Sciences, Graduate School of ScienceOsaka UniversitySuitaJapan
  5. 5.Gatty Marine LaboratoryUniversity of St. AndrewsSt. AndrewsUK

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