Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: Molecular phylogeny and evidence for a new GAD paralog

P T Bosma, M Blazquez, M A Collins, J D D Bishop, G Drouin, I G Priede, K Docherty, V L Trudeau

Research output: Contribution to journalArticle

47 Citations (Scopus)


The evolution of chordate glutamic acid decarboxylase (GAD; EC, a key enzyme in the central nervous system synthesizing the neurotransmitter gamma-amino-butyric acid (GABA) from glutamate, was studied. Prior to this study, molecular data of GAD had been restricted to mammals, which express two distinct forms, GAD(65) and GAD(67). These are the products of separate genes and probably are derived from a common ancestral GAD following gene duplication at some point during vertebrate evolution. To enable a comprehensive phylogenetic analysis, molecular information of GAD forms in other vertebrate classes was essential. By reverse transcriptase-polymerase chain reaction (RT-PCR), partial nucleotide sequences of GAD were cloned from brains of zebra finch (Taeniopygia guttata), turtle (Trachemys scripta), goldfish (Carassius auratus), zebrafish (Danio rerio), and armoured grenadier (Coryphaenoides (Nematonurus) armatus, a deep-sea fish), and from the cerebral ganglion plus neural gland of Ciona intestinalis, a protochordate. Whereas GAD(65) and GAD(67) homologs were expressed in birds, reptiles, and fish, only a single GAD cDNA with equal similarities to both vertebrate GAD forms was found in the protochordate. This indicates that the duplication of the vertebrate GAD gene occurred between 400 and 560 million years ago. For both GAD(65) and GAD(67), the generated phylogenetic tree followed the general tree topology for the major vertebrate classes. In turtle, an alternative spliced form of GAD(65), putatively encoding a truncated, nonactive GAD, was found. Furthermore, a third GAD form, which is equally divergent from both GAD(65) and GAD(67), is expressed in C. (N.) armatus. This third form might have originated from an ancient genome duplication specific to modern ray-finned fishes.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalMolecular Biology and Evolution
Publication statusPublished - 1999


  • glutamic acid decarboxylase
  • GAD
  • gamma-aminobutyric acid
  • neurotransmitter
  • molecular phylogeny
  • chordate evolution
  • 67-KDA GAD
  • CDNA


Dive into the research topics of 'Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: Molecular phylogeny and evidence for a new GAD paralog'. Together they form a unique fingerprint.

Cite this