REPETITIVE DNA-SEQUENCES LOCATED IN THE CENTRAL REGION OF THE HUMAN MDR1 (MULTIDRUG-RESISTANCE) GENE MAY ACCOUNT FOR A GENE FUSION EVENT DURING ITS EVOLUTION

The mdr1 gene, first member of the human multidrug-resistance gene fam ily, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-gly coprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestr al genes during evolution could have resulted in this structure. The D NA sequence analysis of the introns located in the region connecting t he two halves of the human mdr1 gene revealed a highly conserved poly( CA). poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely rep resent ''molecular fossils'' of ancient DNA elements which were involv ed in such a recombination event.