Musset Lise, Le Bras Jacques, Clain Jérôme
Université Paris Descartes, IFR71 Sciences du Médicament, EA209-Eucaryotes pathogènes: Transports membranaires et Chimiorésistances, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Mol Biol Evol. 2007 Aug;24(8):1582-5. doi: 10.1093/molbev/msm087. Epub 2007 May 7.
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.
在此，我们提供了直接证据，表明在暴露于抗疟药物阿托伐醌-氯胍（AP）的独立恶性疟原虫谱系中，细胞色素b基因（pfcytb）同一密码子（268）处的两个适应性核苷酸变化各自反复出现。我们通过对编码pfcytb基因的线粒体（mt）基因组进行测序，分析了来自临床分离株的7个AP抗性等位基因的历史，发现每个AP抗性等位基因都与一个独特的mt单倍型相关。通过比较每个未治愈患者治疗开始前和治疗失败当天分离株的mt序列和微卫星基因型，我们观察到AP抗性等位基因在患者体内出现并传播。这些数据表明，相同的AP抗性等位基因有多个独立起源，并提供了一个由药物治疗选择驱动的恶性疟原虫平行进化的例子。
