IMPLICATION OF THE MULTIDRUG RESISTANCE GENE PFMDR1 IN PLASMODIUM-FALCIPARUM HAS ARISEN AS MULTIPLE INDEPENDENT EVENTS
- Author(s)
- Triglia, T; Foote, SJ; Kemp, DJ; Cowman, AF;
- Details
- Publication Year 1991-10,Volume 11,Issue #10,Page 5244-5250
- Journal Title
- MOLECULAR AND CELLULAR BIOLOGY
- Publication Type
- Journal Article
- Abstract
- The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdrl gene. To investigate the nature and origin of pfmdrl amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdrl, that amplification of the pfmdrl gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure.
- Publisher
- AMER SOC MICROBIOLOGY
- Keywords
- MEROZOITE SURFACE-ANTIGEN; CHLOROQUINE RESISTANCE; ESCHERICHIA-COLI; P-FALCIPARUM; DNA; AMPLIFICATION; SEQUENCE; RECOMBINATION; EXPRESSION; SEPARATION
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Creation Date: 1991-10-01 12:00:00