Skip Navigation



MBE Advance Access published online on May 7, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm087
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
24/8/1582    most recent
msm087v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Musset, L.
Right arrow Articles by Clain, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Musset, L.
Right arrow Articles by Clain, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Letter

Parallel Evolution of Adaptive Mutations in Plasmodium falciparum Mitochondrial DNA During Atovaquone-Proguanil Treatment

Lise Musset1,2, Jacques Le Bras1,2 and Jérôme Clain1

1 Université Paris Descartes, IFR71 Sciences du Médicament, EA209-Eucaryotes pathogènes: Transports membranaires et Chimiorésistances, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
2 Centre National de Référence du Paludisme, APHP, Hôpital Bichat-Claude Bernard, Paris, France

Corresponding author: Jérôme Clain, Address: EA209-Eucaryotes pathogènes: Transports membranaires et Chimiorésistances, Faculté des Sciences Pharmaceutiques et Biologiques, 4 av de l'Observatoire, 75006 Paris, France. E-mail: jerome.clain{at}univ-paris5.fr, Tel: 0033 1 53 73 96 21, Fax: 0033 1 53 73 96 17

Received for publication February 10, 2007. Revision received April 15, 2007. Accepted for publication April 19, 2007.

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.

Key Words: Plasmodium falciparum • atovaquone-proguanil resistance • cytochrome b • parallel evolution


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.