Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Molecular Biology and Evolution Year : 2007

Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment.

Abstract

Here we provide direct evidence that two adaptive nucleotide changes in the same codon (268) of the cytochrome b gene (pfcytb) each occurred repeatedly in independent Plasmodium falciparum lineages exposed to the antimalarial drug atovaquone-proguanil (AP). We analyzed the history of 7 AP resistance alleles from clinical isolates by sequencing the mitochondrial (mt) genome that encodes the pfcytb gene and found that a distinct mt haplotype was associated with each AP resistance allele. By comparing mt sequences and microsatellite genotypes of the isolates both before treatment initiation and at the day of failure for each uncured patient, we observed that the AP resistance alleles occurred and spread within the patients. These data demonstrate that identical AP resistance alleles have multiple independent origins and provide an example of parallel evolution driven by drug treatment selection in P. falciparum.

Domains

Parasitology

Dates and versions

pasteur-00577268 , version 1 (16-03-2011)

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Cite

Lise Musset, Jacques Le Bras, Jérôme Clain. Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment.. Molecular Biology and Evolution, 2007, 24 (8), pp.1582-5. ⟨10.1093/molbev/msm087⟩. ⟨pasteur-00577268⟩

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