Characterization and sequence analysis of the human ornithine decarboxylase gene.

This report describes the characterization and complete sequence of the human ornithine decarboxylase (ODC) gene. Genomic Southern blot analysis shows only a single gene hybridizing at high stringency, in contrast to the murine multigene family. A Pst I restriction fragment length polymorphism was identified and an allele of the human ODC gene containing the polymorphic Pst I site was cloned and sequenced. The ODC gene is divided into 12 exons and spans 8 kb. Comparison of the human, rat, and mouse ODC genes shows striking conservation of genomic organization, as well as 82% identity in the first 148 bp of the 5'-flanking region. This region contains a TATA box, cAMP-responsive element, CCAAT box, and AP-2 binding site and is consistent with induction of ODC gene expression by both the cAMP and protein kinase C-mediated signaling pathways. The first intron of the human gene is 2,849 bp in length, and contains two putative Sp1 binding sites, as well as an Ap1 binding site, suggesting a role for the first intron in transcriptional regulation. The 5' noncoding region of the predicted mRNA contains regions of virtual identity with that of mouse and rat ODC mRNA, suggesting sequences involved in translational regulation. In addition, it was found that the exon segments corresponding to the amino and carboxyl termini of Saccharomyces cerevisiae and Trypanosoma b. brucei are unrelated to their mammalian counterparts, whereas the middle segments of the protein are conserved. These differences may influence the difference in protein half-life seen between T. b. brucei and mammalian ODC.