THE EXON-INTRON ORGANIZATION OF THE GENES (GAD1 AND GAD2) ENCODING 2 HUMAN GLUTAMATE DECARBOXYLASES (GAD(67) AND GAD(65)) SUGGESTS THAT THEY DERIVE FROM A COMMON ANCESTRAL GAD

We have cloned and characterized human genes (GAD1 and GAD2) encoding the two human glutamate decarboxylases, GAD(67) and GAD(65). The coding region of the GAD(65) gene consists of 16 exons, spanning more than 79 kb of genomic DNA. Exon 1 contains the 5' untranslated region of GAD(65) mRNA, and exon 16 specifies the protein's carboxy terminal and at least part of the mRNA's 3' untranslated sequence. Similarly, the coding region of the GAD(67) gene consists of 16 exons, spread over more than 45 kb of genomic DNA. The GAD(67) gene contains an additional exon (exon 0) that, together with part of exon 1, specifies the 5' untranslated region of GAD(67) mRNA. Exon 16 specifies the entire 3' untranslated region of GAD(67) mRNA. EXONS 1-3 encode the most divergent region of GAD65 and GAD(67). The remaining exon-intron boundaries occur at identical positions in the two cDNAs, suggesting that they derive from a common ancestral GAD gene. (C) 1994 Academic Press, Inc.