Update on the aldehyde dehydrogenase gene (ALDH) superfamily

Brian Jackson,Konstandinos Vasiliou,Vasilis Vasiliou,William Black,Chad Brocker,Daniel W Nebert,David C Thompson

doi:10.1186/1479-7364-5-4-283

Abstract

Members of the aldehyde dehydrogenase gene (ALDH) superfamily play an important role in the enzymic detoxification of endogenous and exogenous aldehydes and in the formation of molecules that are important in cellular processes, like retinoic acid, betaine and gamma-aminobutyric acid. ALDHs exhibit additional, non-enzymic functions, including the capacity to bind to some hormones and other small molecules and to diminish the effects of ultraviolet irradiation in the cornea. Mutations in ALDH genes leading to defective aldehyde metabolism are the molecular basis of several diseases, including gamma-hydroxybutyric aciduria, pyridoxine-dependent seizures, Sjögren-Larsson syndrome and type II hyperprolinaemia. Interestingly, several ALDH enzymes appear to be markers for normal and cancer stem cells. The superfamily is evolutionarily ancient and is represented within Archaea, Eubacteria and Eukarya taxa. Recent improvements in DNA and protein sequencing have led to the identification of many new ALDH family members. To date, the human genome contains 19 known ALDH genes, as well as many pseudogenes. Whole-genome sequencing allows for comparison of the entire complement of ALDH family members among organisms. This paper provides an update of ALDH genes in several recently sequenced vertebrates and aims to clarify the associated records found in the National Center for Biotechnology Information (NCBI) gene database. It also highlights where and when likely gene-duplication and gene-loss events have occurred. This information should be useful to future studies that might wish to compare the role of ALDH members among species and how the gene superfamily as a whole has changed throughout evolution.

Highlights

The aldehyde dehydrogenase gene (ALDH) superfamily is represented in all three taxonomic domains (Archaea, Eubacteria and Eukarya), suggesting a vital role throughout evolutionary history
Peptide sequences for each ALDH gene were retrieved from Entrez Protein[12] and aligned against a reference list of ALDH family members, including known human ALDHs and sequences from the National Center for Biotechnology Information (NCBI)’s HomoloGene[12] using ClustalW.[13]
Names were assigned to the ‘new genes’ and ‘pseudogenes’ (Table 3) according to the ALDH nomenclature system established in 1999.14 The species-specific nomenclature system was used for zebrafish genes.[15]

Summary

Introduction

The aldehyde dehydrogenase gene (ALDH) superfamily is represented in all three taxonomic domains (Archaea, Eubacteria and Eukarya), suggesting a vital role throughout evolutionary history. Our understanding of the biological roles of this superfamily continues to expand in ways that are often unexpected and, perhaps, unprecedented for an enzyme family. As implied by their name, members of this superfamily serve to metabolise both physiologically and pathophysiologically relevant aldehydes. This capacity prevents the accumulation of toxic aldehydes derived from endogenous production and/or exogenous exposures, which, if left unchecked, adversely affect cellular homeostasis and organismal functions.[1].

Methods

Results

Conclusion