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 family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the 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 represent "molecular fossils" of ancient DNA elements which were involved in such a recombination event.
Pauly
M
M
Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Centre Universitaire de Luxembourg, Grand-Duchy of Luxembourg.
Kayser
I
I
Schmitz
M
M
Ries
F
F
Hentges
F
F
Dicato
M
M
D001483:Base Sequence; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D017421:Sequence Analysis