The Xenopus alcohol dehydrogenase gene family: characterization and comparative analysis incorporating amphibian and reptilian genomes

BMC Genomics

Jaume Farrés¹  Xavier Parés¹  Gregg Duester²  Ricard Albalat³  Emma Borràs¹ 

[1] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, E-08193, Bellaterra, Barcelona, Spain;Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA;Departament de Gènetica, Facultat de Biologia and Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona, Av. Diagonal, E-08028, Barcelona, Spain

关键词: Vertebrate evolution;    Gene family;    Enzymogenesis;    Alcohol dehydrogenase;   

Others  :  1217664
DOI  :  10.1186/1471-2164-15-216

 received in 2013-10-04, accepted in 2014-03-11,  发布年份 2014

【 摘 要 】

Background

The alcohol dehydrogenase (ADH) gene family uniquely illustrates the concept of enzymogenesis. In vertebrates, tandem duplications gave rise to a multiplicity of forms that have been classified in eight enzyme classes, according to primary structure and function. Some of these classes appear to be exclusive of particular organisms, such as the frog ADH8, a unique NADP⁺-dependent ADH enzyme. This work describes the ADH system of Xenopus, as a model organism, and explores the first amphibian and reptilian genomes released in order to contribute towards a better knowledge of the vertebrate ADH gene family.

Results

Xenopus cDNA and genomic sequences along with expressed sequence tags (ESTs) were used in phylogenetic analyses and structure-function correlations of amphibian ADHs. Novel ADH sequences identified in the genomes of Anolis carolinensis (anole lizard) and Pelodiscus sinensis (turtle) were also included in these studies. Tissue and stage-specific libraries provided expression data, which has been supported by mRNA detection in Xenopus laevis tissues and regulatory elements in promoter regions. Exon-intron boundaries, position and orientation of ADH genes were deduced from the amphibian and reptilian genome assemblies, thus revealing syntenic regions and gene rearrangements with respect to the human genome. Our results reveal the high complexity of the ADH system in amphibians, with eleven genes, coding for seven enzyme classes in Xenopus tropicalis. Frogs possess the amphibian-specific ADH8 and the novel ADH1-derived forms ADH9 and ADH10. In addition, they exhibit ADH1, ADH2, ADH3 and ADH7, also present in reptiles and birds. Class-specific signatures have been assigned to ADH7, and ancestral ADH2 is predicted to be a mixed-class as the ostrich enzyme, structurally close to mammalian ADH2 but with class-I kinetic properties. Remarkably, many ADH1 and ADH7 forms are observed in the lizard, probably due to lineage-specific duplications. ADH4 is not present in amphibians and reptiles.

Conclusions

The study of the ancient forms of ADH2 and ADH7 sheds new light on the evolution of the vertebrate ADH system, whereas the special features showed by the novel forms point to the acquisition of new functions following the ADH gene family expansion which occurred in amphibians.

【 授权许可】

   
2014 Borràs et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Persson B, Zigler JS Jr, Jörnvall H: A super-family of medium-chain dehydrogenases/reductases (MDR). Sub-lines including zeta-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductase enoyl reductases, VAT-1 and other proteins. Eur J Biochem 1994, 226:15-22.
• [2]Duester G, Farrés J, Felder MR, Holmes RS, Höög JO, Parés X, Plapp BV, Yin SJ, Jörnvall H: Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Biochem Pharmacol 1999, 58:389-395.
• [3]ADH gene nomenclature approved by the Human Genome Organization (HUGO) Gene Nomenclature Committeehttp://www.genenames.org/genefamilies/ADH webcite
• [4]Gonzàlez-Duarte R, Albalat R: Merging protein, gene and genomic data: the evolution of the MDR-ADH family. Heredity 2005, 95:184-197.
• [5]Cederlund E, Hedlund J, Hjelmqvist L, Jonsson A, Shafqat J, Norin A, Keung WM, Persson B, Jörnvall H: Characterization of new medium-chain alcohol dehydrogenases adds resolution to duplications of the class I/III and the sub-class I genes. Chem Biol Interact 2011, 191:8-13.
• [6]Li TK, Bosron WF, Dafeldecker WP, Lange LG, Vallee BL: Isolation of PI-alcohol dehydrogenase of human liver: is it a determinant of alcoholism? Proc Natl Acad Sci U S A 1977, 74:4378-4381.
• [7]Yang ZN, Davis GJ, Hurley TD, Stone CL, Li TK, Bosron WF: Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction. Alcohol Clin Exp Res 1994, 18:587-591.
• [8]Allali-Hassani A, Peralba JM, Martras S, Farrés J, Parés X: Retinoids, ω-hydroxyfatty acids and cytotoxic aldehydes as physiological substrates, and H2-receptor antagonists as pharmacological inhibitors, of human class IV alcohol dehydrogenase. FEBS Lett 1998, 426:362-366.
• [9]Downes JE, Vandeberg JL, Hubbard GB, Holmes RS: Regional distribution of mammalian corneal aldehyde dehydrogenase and alcohol dehydrogenase. Cornea 1992, 11:560-566.
• [10]Haselbeck RJ, Ang HL, Duester G: Class IV alcohol/retinol dehydrogenase localization in epidermal basal layer: potential site of retinoic acid synthesis during skin development. Dev Dyn 1997, 208:447-453.
• [11]Vaglenova J, Martínez SE, Porté S, Duester G, Farrés J, Parés X: Expression, localization and potential physiological significance of alcohol dehydrogenase in the gastrointestinal tract. Eur J Biochem 2003, 270:2652-2662.
• [12]Höög JO, Brandt M, Hedberg JJ, Strömberg P: Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat ADH6. Chem Biol Interact 2001, 130–132:395-404.
• [13]Höög JO, Östberg LJ: Mammalian alcohol dehydrogenases – a comparative investigation at gene and protein levels. Chem Biol Interact 2011, 191:2-7.
• [14]Kedishvili NY, Gough WH, Chernoff EA, Hurley TD, Stone CL, Bowman KD, Popov KM, Bosron WF, Li TK: cDNA sequence and catalytic properties of a chick embryo alcohol dehydrogenase that oxidizes retinol and 3β,5α-hydroxysteroids. J Biol Chem 1997, 272:7494-7500.
• [15]Peralba JM, Cederlund E, Crosas B, Moreno A, Julià P, Martínez SE, Persson B, Farrés J, Parés X, Jörnvall H: Structural and enzymatic properties of a gastric NADP(H)-dependent and retinal-active alcohol dehydrogenase. J Biol Chem 1999, 274:26021-26026.
• [16]Wesolowski MH, Lyerla TA: Alcohol dehydrogenase isozymes in the clawed frog. Xenopus laevis. Biochem Genet 1983, 21:1003-1017.
• [17]Graf JD: Genetic mapping in Xenopus laevis: eight linkage groups established. Genetics 1989, 123:389-398.
• [18]Peralba JM, Crosas B, Martínez SE, Julià P, Farrés J, Parés X: Amphibian alcohol dehydrogenase. Purification and characterization of classes I and III from Rana perezi. Adv Exp Med Biol 1999, 463:343-358.
• [19]Rosell A, Valencia E, Ochoa WF, Fita I, Parés X, Farrés J: Complete reversal of coenzyme specificity by concerted mutation of three consecutive residues in alcohol dehydrogenase. J Biol Chem 2003, 278:40573-40580.
• [20]Valencia E, Rosell A, Larroy C, Farrés J, Biosca JA, Fita I, Parés X, Ochoa WF: Crystallization and preliminary X-ray analysis of NADP(H)-dependent alcohol dehydrogenases from Saccharomyces cereviasiae and Rana perezi. Acta Cryst D Biol Cryst 2003, 59:334-337.
• [21]Rosell A, Valencia E, Parés X, Fita I, Parés X, Farrés J, Ochoa WF: Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8). J Mol Biol 2003, 330:75-85.
• [22]Hoffmann I, Ang HL, Duester G: Alcohol dehydrogenase in Xenopus development: conserved expression of ADH1 and ADH4 in epithelial retinoid targed tissues. Dev Dyn 1998, 213:261-270.
• [23]Persson B, Hedlund J, Jörnvall H: The MDR superfamily. Cell Mol Life Sci 2008, 65:3879-3894.
• [24]Close B, Banister K, Baumans V, Bernoth EM, Bromage N, Bunyan J, Erhardt W, Flecknell P, Gregory N, Hackbarth H, Morton D, Warwick C: Recommendations for euthanasia of experimental animals: part 2. DGTX of the European Commission. Lab Anim 1997, 31:1-32.
• [25]Frohman MA: Rapid amplification of cDNA ends for generation of full-length cDNAs: thermal RACE. Methods Enzymol 1993, 218:340-356.
• [26]Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-cloroform extraction. Anal Biochem 1987, 162:156-159.
• [27]Boleda MD, Julià P, Moreno A, Parés X: Role of extrahepatic alcohol dehydrogenase in rat ethanol metabolism. Arch Biochem Biophys 1989, 274:74-81.
• [28]UniProthttp://www.uniprot.org webcite
• [29]Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 1990, 215:403-410.
• [30]TBLASTN search at Sanger Institute X. tropicalis EST Projecthttp://www.sanger.ac.uk/cgi-bin/blast/submitblast/x_tropicalis webcite
• [31]BLAST search at TGI Gene Indices[http://compbio.dfci.harvard.edu/cgi-bin/tgi/Blast/index.cgi webcite]
• [32]UniGenehttp://www.ncbi.nlm.nih.gov/unigene webcite
• [33]TBLASTN search at Joint Genome Institute X. tropicalis Genome Assembly 4.1http://genome.jgi-psf.org/pages/blast.jsf?db=Xentr4 webcite
• [34]TBLASTN search at Ensembl genome browserhttp://www.ensembl.org/Multi/blastview webcite
• [35]Kent WJ: BLAT–the BLAST-like alignment tool. Genome Res 2002, 12:656-664.
• [36]BLAT search at UCSC web browserhttp://genome.ucsc.edu/cgi-bin/hgBlat webcite
• [37]Ensembl genome browserhttp://www.ensembl.org webcite
• [38]Kel AE, Grossling E, Reuter I, Cheremushkin E, Kel-Margoulis OV, Wingender E: MATCH: a tool for searching transcription binding sites in DNA sequences. Nucleic Acids Res 2003, 31:3576-3579.
• [39]Hall TA: BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 1999, 41:95-98.
• [40]Sievers F, Wilm A, Dineen DG, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG: Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 2011, 7:539.
• [41]Clustal Omega web formhttps://www.ebi.ac.uk/Tools/msa/clustalo webcite
• [42]Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011, 28:2731-2739.
• [43]Saitou N, Nei M: The neighbour-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987, 4:406-425.
• [44]Jones DT, Taylor WR, Thornton JM: The rapid generation of mutation data matrices from protein sequences. CABIOS 1992, 8:275-282.
• [45]Strimmer K, von Haesler A: Quartet puzzling: a quartet maximum likelihood method for reconstructing tree topologies. Mol Biol Evol 1996, 13:964-969.
• [46]Felsenstein J: Confidence limits on phylogenies: an approach using the bootstrap. Evolution 1985, 39:783-791.
• [47]Felsenstein J: Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet 1988, 22:521-565.
• [48]Guindon S, Gascuel O: A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 2003, 52:696-704.
• [49]European Molecular Biology Laboratory (EMBL) nucleotide sequence databasehttp://www.ebi.ac.uk webcite
• [50]Zgômbic-Knight M, Foglio MH, Duester G: Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro. J Biol Chem 1995, 270:4305-4311.
• [51]Duester G, Smith M, Bilanchone V, Hatfield GW: Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the β subunit. J Biol Chem 1986, 261:2027-2033.
• [52]Stewart MJ, McBride MS, Winter LA, Duester G: Promoters for the human alcohol dehydrogenase genes ADH1, ADH2 and ADH3: Interaction of CCAAT/enhancer binding protein with elements flanking the ADH2 TATA box. Gene 1990, 90:271-279.
• [53]Ceci JD, Zheng YW, Felder MR: Molecular analysis of mouse alcohol dehydrogenase: nucleotide sequence of the Adh-1 gene and genetic mapping of a related nucleotide sequence to chromosome 3. Gene 1987, 59:181-182.
• [54]Zhang K, Bosron WF, Edenberg HJ: Structure of the mouse Adh-1 gene and identification of a deletion in a long alternating purine-pyrimidine sequence in the first intron of strains expressing low alcohol dehydrogenase activity. Gene 1987, 57:27-36.
• [55]Von Bahr-Lindström H, Jörnvall H, Höög JO: Cloning and characterization of the human ADH4 gene. Gene 1991, 103:269-274.
• [56]Foglio MH, Duester G: Characterization of the functional gene encoding mouse class III alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) and an unexpressed processed pseudogene with an intact open reading frame. Eur J Biochem 1996, 237:496-504.
• [57]Hur MW, Edenberg HJ: Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase. Gene 1992, 121:305-311.
• [58]Hur MW, Edenberg HJ: Cell-specific function of cis-acting elements in the regulation of human alcohol dehydrogenase 5 gene expression and effect of the 5′-nontranslated region. J Biol Chem 1995, 270:9002-9009.
• [59]Dannenberg LO, Chen HJ, Edenberg HJ: GATA-2 and HNF-3beta regulate the human alcohol dehydrogenase 1A (ADH1A) gene. DNA Cell Biol 2005, 24:543-552.
• [60]Schule R, Rangarajan P, Yang N, Kliewer S, Ransone LJ, Bolado J, Verma IM, Evans RM: Retinoic acid is a negative regulador of AP-1-reponsive genes. Proc Natl Acad Sci U S A 1991, 88:6092-6096.
• [61]International Chicken Genome Sequencing Consortium: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 2004, 432:695-716.
• [62]Hughes MK, Hughes AL: Evolution of duplicate genes in a tetraploid animal. Xenopus laevis. Mol Biol Evol 1993, 10:1360-1369.
• [63]Hosbach HA, Wyler T, Weber R: The Xenopus laevis globin gene family: chromosomal arrangement and gene structure. Cell 1983, 32:45-53.
• [64]Stutz F, Spohr G: A processed gene coding for a sarcomeric actin in Xenopus laevis and Xenopus tropicalis. EMBO J 1987, 6:1989-1995.
• [65]Eklund H, Müller-Wille P, Horjales E, Futer O, Holmquist B, Vallee BL, Höög JO, Kaiser R, Jörnvall H: Comparison of three classes of human liver alcohol dehydrogenases. Emphasis on different substrate binding pockets. Eur J Biochem 1990, 193:303-310.
• [66]Hurley TD, Bosron WF: Human alcohol dehydrogenase: dependence of secondary alcohol oxidation on the amino acids at positions 93 and 94. Biochem Biophys Res Commun 1992, 183:93-99.
• [67]Domínguez M, Álvarez R, Borràs E, Farrés J, Parés X, de Lera AR: Synthesis of enantiopure C3– and C4-hydroxyretinals and their enzymatic reduction by ADH8 from Xenopus laevis. Org Biomol Chem 2006, 4:155-164.
• [68]Nei M, Kumar S: Molecular Evolution and Phylogenies. New York: Oxford University Press; 2000.
• [69]Hjelmqvist L, Estonius M, Jörnvall H: The vertebrate alcohol dehydrogenase system: variable class II type form elucidates separate stages of enzymogenesis. Proc Natl Acad Sci U S A 1995, 92:10904-10908.
• [70]Svensson S, Strömberg P, Höög JO: A novel subtype of class II alcohol dehydrogenase in rodents. Unique Pro47 and Ser182 modulates hydride transfer in the mouse enzyme. J Biol Chem 1999, 274:29712-29719.
• [71]Hellgren M, Strömberg P, Gallego O, Martras S, Farrés J, Persson B, Parés X, Höög JO: Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinoid metabolism. Cell Mol Life Sci 2007, 64:498-505.
• [72]Yang ZN, Bosron WF, Hurley TD: Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase. J Mol Biol 1997, 265:330-343.
• [73]Sanghani PC, Bosron WF, Hurley TD: Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation. Biochemistry 2002, 41:15189-15194.
• [74]Cañestro C, Godoy L, Gonzàlez-Duarte R, Albalat R: Comparative expression analysis of Adh3 during arthropod, urochordate, cephalochordate, and vertebrate development challenges its predicted housekeeping role. Evol Dev 2003, 5:157-162.
• [75]Dasmahapatra AK, Doucet HL, Bhattacharyya C, Carvan MJ: Development expression of alcohol dehydrogenase (ADH3) in zebrafish (Danio rerio). Biochem Biophys Res Commun 2001, 286:1082-1086.
• [76]Farrés J, Moreno A, Crosas B, Peralba JM, Allali-Hassani A, Hjelmqvist L, Jörnvall H, Parés X: Alcohol dehydrogenase of class IV (σσ-ADH) from human stomach. cDNA sequence and structure/function relationships. Eur J Biochem 1994, 224:549-557.