Functional Diversification and Evolution of Animal Zinc‐Dependent Alcohol Dehydrogenases

Abstract

Zinc‐dependent alcohol dehydrogenases (ADHs) comprise one of the best studied group of enzymes. Vertebrates possess eight distinct classes (I‐VIII) of ADHs, based upon sequence homology, catalytic activity and gene expression features. However, because many independent duplications occurred along the evolution of vertebrates, the identification of orthologous groups of proteins is not convincingly resolved. Since the number of ADH sequences in animals has been duplicated after the last analysis of these enzymes, a new phylogenetic analysis was performed.Results provide a comprehensive scenario, where is clear that ancestral class III ADH give rise in first place to the class I ADH, which is present in all classes of vertebrates. Later, class II and VII emerged by duplication of class III ADH before the amphibian‐amniota split, but interestingly, class VII ADH was lost in mammals. Finally, classes IV to VI have a more recent origin, because the duplication that gave rise to these three classes occurred just after the appearance of mammals. Class VIII ADH is restricted only to amphibians.The complex ADHs enzymogenesis in vertebrates is a consequence of the diverse physiological roles developed by these enzymes, as responsible to synthesize or catabolize several endogenous metabolites that regulate growth, metabolism, differentiation and neuroendocrine functions. Supported by DGAPA‐UNAM grant IN208308