THE LONG LEADER SEQUENCE OF THE MOUSE ORNITHINE DECARBOXYLASE MESSENGER-RNA, PREVIOUSLY SUSPECTED TO BE A CLONING ARTIFACT, IS PROBABLY A PRODUCT OF RECOMBINATION WITH A MULV-LIKE RETROVIRUS

Sequence analysis of the first 549 nucleotides (nt) of the non-translated 5' end of the cloned mouse ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17)-encoding sequence shows that this sequence is closely related to nt 1946-1395 of Moloney murine leukemia virus (MuLV). The viral sequence, however, is oriented anti-sense relative to the ODC sequence. This orientation makes it unlikely to be a cloning artifact mediated by reverse transcriptase, but rather a recombination between genomic DNA and a MuLV-like provirus. In the cell line, from which the cDNA clone originated, Katz and Kahana [EMBO J. 8 (1989) 1163-1167] have shown that an intragenic deletion and amplification of the ODC gene had taken place. We believe that an additional recombination also has occurred in this cell line. The cDNA clone studied was obtained after selecting for high ODC expression. It is conceivable that the retroviral sequence contains an, intragenic enhancer which is also functional in the anti-sense orientation. The inserted sequence contains two repeats which share homology with known enhancer elements. The reported recombination event shows that caution is needed when selective pressure is applied for the isolation and characterization of genes.