Update on the aldehyde dehydrogenase gene (ALDH) superfamily

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.

Figure 1

Neighbour-joining dendrogram (with branch lengths representing relative protein sequence similarity) of ALDH3B sequences in human, rat and mouse, indicating the likely homology and identity of the genes assigned 'Aldh3b3' in rat and mouse.

Figure 2

Comparison of ALDH4A1 from human and rat. Rat Aldh4a1 is part of the larger fusion gene LRRP Ba1-651 [26]. The exons representing the Aldh4a1 portion of this gene with homology to mouse and human are highlighted.

Figure S1

Alignment of ALDH3B2 genes in human, rat and mouse created by ClustalW. Dashes (-) represent sequence gaps, asterisks (*) represent identical amino acids (AAs), colons (:) represent very similar AAs, periods (.) represent less similar AAs, whereas spaces () represent dissimilar AAs.