Physical linkage to drug resistance genes results in conservation of var genes among West Pacific Plasmodium falciparum isolates

J Infect Dis. 2006 Oct 1;194(7):939-48. doi: 10.1086/506619. Epub 2006 Aug 23.

Abstract

The multicopy var gene family encoding the variant surface antigen Plasmodium falciparum erythrocyte membrane protein 1 is highly diverse, with little overlap between different P. falciparum isolates. We report 5 var genes (varS1-varS5) that are shared at relatively high frequency among 63 genetically diverse P. falciparum isolates collected from 5 islands in the West Pacific region. The varS1, varS2, and varS3 genes were localized to the internal region on chromosome 4, approximately 200 kb from pfdhfr-ts, whereas varS4 and varS5 were mapped to an internal region of chromosome 7, within 100 kb of pfcrt. The presence of varS2 and varS3 were significantly correlated with the pyrimethamine-resistant pfdhfr genotype, whereas varS4 was strongly correlated with the chloroquine-resistant pfcrt genotype. Thus, the conservation of these var genes is the result of their physical linkage with drug-resistant genes in combination with the antimalarial drug pressure in the region.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimalarials / pharmacology*
  • Asia, Southeastern
  • Chloroquine / pharmacology
  • Chromosome Mapping*
  • Conserved Sequence*
  • Drug Resistance / genetics*
  • Electrophoresis, Gel, Pulsed-Field
  • Genetic Linkage*
  • Humans
  • Pacific Islands
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / isolation & purification
  • Protozoan Proteins / genetics*
  • Pyrimethamine / pharmacology

Substances

  • Antimalarials
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Chloroquine
  • Pyrimethamine