Complex Polymorphisms in an Approximately 330 kDa Protein Are Linked to Chloroquine-Resistant P. Falciparum in Southeast Asia and Africa

Cell. 1997 Nov 28;91(5):593-603. doi: 10.1016/s0092-8674(00)80447-x.

Abstract

Chloroquine resistance in a P. falciparum cross maps as a Mendelian trait to a 36 kb segment of chromosome 7. This segment harbors cg2, a gene encoding a unique approximately 330 kDa protein with complex polymorphisms. A specific set of polymorphisms in 20 chloroquine-resistant parasites from Asia and Africa, in contrast with numerous differences in 21 sensitive parasites, suggests selection of a cg2 allele originating in Indochina over 40 years ago. One chloroquine-sensitive clone exhibited this allele, suggesting another resistance component. South American parasites have cg2 polymorphisms consistent with a separate origin of resistance. CG2 protein is found at the parasite periphery, a site of chloroquine transport, and in association with hemozoin of the digestive vacuole, where chloroquine inhibits heme polymerization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Africa
  • Amino Acid Sequence
  • Animals
  • Antimalarials / pharmacology*
  • Asia, Southeastern
  • Chloroquine / pharmacology*
  • Chromosome Mapping
  • Crossing Over, Genetic
  • DNA, Protozoan / analysis
  • DNA, Satellite / analysis
  • Drug Resistance, Microbial
  • Erythrocytes / parasitology
  • Genetic Linkage
  • Molecular Sequence Data
  • Pan troglodytes
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Polymorphism, Genetic
  • Protozoan Proteins / analysis
  • Protozoan Proteins / genetics*
  • Sequence Analysis, DNA
  • Transcription, Genetic

Substances

  • Antimalarials
  • CG1 protein, Plasmodium falciparum
  • CG2 protein, Plasmodium falciparum
  • DNA, Protozoan
  • DNA, Satellite
  • Protozoan Proteins
  • Chloroquine

Associated data

  • GENBANK/AF030690
  • GENBANK/AF030691
  • GENBANK/AF030692
  • GENBANK/AF030693
  • GENBANK/AF030694
  • GENBANK/AF033378