title: Physical linkage to drug resistance genes results in conservation of var genes among West Pacific Plasmodium falciparum isolates.
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.
authors.affiliation: Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Fowler
authors.forename: Marina
authors.initials: M
authors.lastname: Chavchich
authors.forename: Nanhua
authors.initials: N
authors.lastname: Chen
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Peters
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gatton
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001210:Asia, Southeastern; D002738:Chloroquine / Q000494:pharmacology; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004351:Drug Resistance / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D008040:Genetic Linkage; D006801:Humans; D010139:Pacific Islands; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002738:Chloroquine; D011739:Pyrimethamine