Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins.

摘要: The MDR1 gene, responsible for multidrug resistance in human cells, encodes a broad specificity efflux pump (P-glycoprotein). P-glycoprotein consists of two similar halves, each half including hydrophobic transmembrane region and nucleotide-binding domain. On the basis sequence homology between N-terminal C-terminal halves P-glycoprotein, we have previously suggested that this gene arose by duplication primordial gene. We now determined complete intron/exon structure direct sequencing cosmid clones enzymatic amplification genomic DNA segments. includes 28 introns, 26 which interrupt protein-coding sequence. Although both are composed approximately same number exons, only intron pairs, within domains, located at conserved positions protein. other introns occur different locations protein most cases coding relative to open reading frame. These results suggest fusion genes related but independently evolved proteins rather than internal duplication.