Comparative Studies of Vertebrate Mitochondrial Carbonic Anhydrase (CA5) Genes and Proteins: Evidence for Gene Duplication in Mammals with CA5A Being Liver Specific and CA5B Broadly Expressed and Located on the X-Chromosome

Abstract

At least fifteen families of mammalian carbonic anhydrases (CA) (E.C. 4.2.1.2) catalyse the hydration of carbon dioxide and related functions. CA5A and CA5B genes encode distinct mitochondrial enzymes and perform essential biochemical roles, including ammonia detoxification and glucose metabolism. Bioinformatic methods were used to predict the amino acid sequences, secondary structures and gene locations for CA5A and CA5B genes and proteins using data from vertebrate genome projects. CA5A and CA5B genes usually contained 7 coding exons for each of the vertebrate genomes examined. Human CA5A and CA5B subunits contained 305 and 317 amino acids, respectively, with key amino acid residues including mitochondrial transit peptides; three Zinc binding sites (His130, His132, His155); and a Tyr164 active site. Phylogenetic analyses of vertebrate CA5 gene families suggested that it is an ancient gene in vertebrate evolution which had undergone a gene duplication event in a mammalian ancestral genome forming the CA5A and CA5B gene families in monotreme, marsupial and eutherian mammals. CA5A was predominantly expressed in liver whereas CA5B had a wide tissue distribution profile, was localized on the X-chromosome and was more highly conserved during mammalian evolution.