Abstract
BackgroundThe 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.ResultsXenopus 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.ConclusionsThe 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.
Highlights
The alcohol dehydrogenase (ADH) gene family uniquely illustrates the concept of enzymogenesis
By Reverse transcription-polymerase chain reaction (RT-PCR) amplification from a X. laevis stomach cDNA pool, four cDNAs were cloned and sequenced, and, on the basis of amino acid sequence identity, they were assigned to ADH1, ADH3, ADH8 and a novel ADH9 class
ADH1, ADH3 and ADH8 were similar to their R. perezi orthologues and showed the typical residues of each class, while the low sequence identity values (
Summary
The alcohol dehydrogenase (ADH) gene family uniquely illustrates the concept of enzymogenesis. 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. Vertebrate alcohol dehydrogenases (ADH, EC1.1.1.1) are dimeric zinc-containing enzymes with a 40-kDa subunit and 373–383 amino acid residues. They belong to the medium-chain dehydrogenase/reductase (MDR) superfamily [1]. ADH8 is a unique NADP+-dependent ADH isolated from the stomach of the frog Rana perezi and its proposed function is the reduction of retinaldehyde to retinol [15]
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