title: Comparative and evolutionary studies of ALDH18A1 genes and proteins.
abstract: Vertebrate ALDH18A1 genes encode a bifunctional mitochondrial enzyme, catalyzing a 2-step conversion of glutamate to glutamyl semialdehyde, subsequently converted into proline, ornithine and arginine. Bioinformatic analyses of vertebrate and invertebrate genomes were undertaken using known ALDH18A1 amino acid sequences. G5K (glutamyl kinase) and GPR (glutamyl phosphate reductase) domain sequences were identified for all vertebrate and invertebrate genomes examined, whereas bacterial sequences encoded separate enzymes. Vertebrate ALDH18A1 (also called P5CS) sequences were highly conserved throughout vertebrate evolution. A mechanism for generating two major vertebrate ALDH18A1 isoforms is proposed with 'a' isoform containing Asn239-Val240 with wide tissue expression, whereas the 'b' isoform lacking the dipeptide has been reported in gut tissues. Phylogenetic analyses describe the relationships and potential origins of the ALDH18A1 gene during vertebrate and invertebrate evolution and a proposal for generating the bifunctional vertebrate and invertebrate ALDH18A1 gene from a bacterial operon (proBA) encoding G5K and GPR. A more recent Aldh18a1 gene duplication event has apparently occurred with a primordial rat genome.
authors.affiliation: The Griffith Institute for Drug Discovery and School of Natural Sciences, Griffith University, Nathan 4111, QLD, Australia. Electronic address: r.holmes@griffith.edu.au.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Holmes
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016208:Databases, Factual; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D007448:Invertebrates / Q000145:classification / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D000072417:Protein Domains / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014714:Vertebrates / Q000145:classification / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D000444:Aldehyde Dehydrogenase
keywords: ALDH18A1; Aldehyde dehydrogenases; Bifunctional enzyme; CpG islands; Evolution; GK; GPR; Gene integration; Glutamyl kinase; Glutamyl phosphate reductase; Invertebrates; Phylogeny; Primordial gene; Transcription factor binding sites; Vertebrates