Skip Navigation



MBE Advance Access published online on May 25, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi177
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
22/9/1834    most recent
msi177v1
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 Pearce, R.
Right arrow Articles by Roper, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pearce, R.
Right arrow Articles by Roper, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. 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@oupjournals.org
Accepted May 23, 2005

Research Article

Reduced Variation Around Drug Resistant dhfr Alleles in African Plasmodium falciparum

Richard Pearce 1*, Allen Malisa 2, S. Patrick Kachur 3, Karen Barnes 4, Brian Sharp 5, and Cally Roper 1

1 London School of Hygiene and Tropical Medicine, Pathogen Molecular Biology Unit, Department of Infectious Tropical Diseases, Keppel Street, London, WC1E 7HT, United Kingdom
2 University of Morogoro, Department of Biological Sciences, Faculty of Science, SUA, P O Box 3038, Morogoro, Tanzania; Ifakara Health Research and Development Centre, PO Box 53, Ifakara, Tanzania
3 Ifakara Health Research and Development Centre, PO Box 53, Ifakara, Tanzania; Malaria Branch, Division of Parasitic Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway NE, MS F-22, Atlanta, Georgia, United States, 30341
4 University of Cape Town Division of Clinical Pharmacology, Anzio Road, Observatory, 7925, Cape Town, South Africa
5 Malaria Research Lead Programme, Medical Research Council, PO Box 70380, Overport 4067, Durban, South Africa

* To whom correspondence should be addressed.
Richard Pearce, E-mail: richard.pearce{at}lshtm.ac.uk


  Abstract

We have measured microsatellite diversity at 26 markers around the dhfr gene in pyrimethamine sensitive and resistant parasites collected in SE Africa. Through direct comparison with diversity on ancestral comparisons we have found significant loss of diversity across a region of 70kb around the most highly resistant allele which is evidence of a selective sweep attributable to selection through widespread use of pyrimethamine (in combination with Sulfadoxine) as treatment for malaria. Retrospective analysis through five years of direct and continuous selection from use of sulfadoxine-pyrimethamine as first- line malaria treatment on a Plasmodium falciparum population in KwaZulu Natal, South Africa, has revealed how recombination significantly narrowed the margins of the selective sweep over time. A deterministic model incorporating selection coefficients measured during the same interval indicates that the transition was towards a state of recombination-selection equilibrium. We compared loss of diversity around the same resistance allele in two populations at either extreme of the range of entomological inoculation rates (EIR), namely under one infective bite per year in Mpumalanga, South Africa, and more than one per day in southern Tanzania. Entomological inoculation rates determine effective recombination rates and are expected to profoundly influence the dimensions of the selective sweep. Surprisingly the dimensions were broadly consistent across both populations. We conclude that despite different recombination rates and contrasting drug selection histories in neighboring countries, the region-wide movement of resistant parasites has played a key role in the establishment of resistance in these populations and the dimensions of the selective sweep are dominated by the influence of high initial starting frequencies.

Keywords: Plasmodium falciparum; selective sweeps; pyrimethamine resistance.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am J Trop Med HygHome page
V. N. Hawkins, S. M. Suzuki, K. Rungsihirunrat, H. C. Hapuarachchi, A. Maestre, K. Na-Bangchang, and C. H. Sibley
Assessment of the Origins and Spread of Putative Resistance-Conferring Mutations in Plasmodium vivax Dihydropteroate Synthase
Am J Trop Med Hyg, August 1, 2009; 81(2): 348 - 355.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
A. M. McCollum, L. K. Basco, R. Tahar, V. Udhayakumar, and A. A. Escalante
Hitchhiking and Selective Sweeps of Plasmodium falciparum Sulfadoxine and Pyrimethamine Resistance Alleles in a Population from Central Africa
Antimicrob. Agents Chemother., November 1, 2008; 52(11): 4089 - 4097.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Annan, P. Durand, F. J. Ayala, C. Arnathau, P. Awono-Ambene, F. Simard, F. G. Razakandrainibe, J. C. Koella, D. Fontenille, and F. Renaud
Population genetic structure of Plasmodium falciparum in the two main African vectors, Anopheles gambiae and Anopheles funestus
PNAS, May 8, 2007; 104(19): 7987 - 7992.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Mita, K. Tanabe, N. Takahashi, T. Tsukahara, H. Eto, L. Dysoley, H. Ohmae, K. Kita, S. Krudsood, S. Looareesuwan, et al.
Independent Evolution of Pyrimethamine Resistance in Plasmodium falciparum Isolates in Melanesia
Antimicrob. Agents Chemother., March 1, 2007; 51(3): 1071 - 1077.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
D. J. Conway
Molecular Epidemiology of Malaria
Clin. Microbiol. Rev., January 1, 2007; 20(1): 188 - 204.
[Abstract] [Full Text] [PDF]


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.