Evolutionary paradigm of chloroquine-resistant malaria in India.
Drug pressure in the field is believed to be responsible for the emergence of drug-resistant Plasmodium falciparum, the parasite that causes malaria. Variants of the P. falciparum chloroquine resistance transporter (pfcrt) gene have been shown to be responsible for conferring resistance to the commonly used drug chloroquine. In particular, an amino acid mutation, K76T, was shown to have a strong positive correlation with the chloroquine-resistant varieties of malaria parasites. Global studies have reported highly reduced genetic diversity surrounding K76T in the pfcrt gene, which indicates that the mutation has been a target of positive Darwinian natural selection. However, two recent studies of P. falciparum in India found high genetic diversity in the pfcrt gene, which, at first sight, do not support the role of natural selection in the evolution of chloroquine resistance in India.
Das
Aparup
A
Evolutionary Genomics and Bioinformatics Laboratory, National Institute of Malaria Research, 22 Sham Nath Marg, Delhi 110054, India. aparup@mrcindia.org
Dash
Aditya Prasad
AP
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D012641:Selection, Genetic
D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine