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Title: Whole-genome scans provide evidence of adaptive evolution in malawian Plasmodium falciparum isolates
Authors: Harold Ocholla
Mark D. Preston
Mwapatsa Mipando
Anja T.R. Jensen
Susana Campino
Bronwyn Macinnis
Daniel Alcock
Anja Terlouw
Issaka Zongo
Jean Bosco Oudraogo
Abdoulaye A. Djimde
Samuel Assefa
Ogobara K. Doumbo
Steffen Borrmann
Alexis Nzila
Kevin Marsh
Rick M. Fairhurst
Francois Nosten
Tim J.C. Anderson
Dominic P. Kwiatkowski
Alister Craig
Taane G. Clark
Jacqui Montgomery
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
University of Malawi
Liverpool School of Tropical Medicine
London School of Hygiene & Tropical Medicine
Wellcome Trust Sanger Institute
Wellcome Trust Centre for Human Genetics
Kobenhavns Universitet
Copenhagen University Hospital
Institut de Recherche en Sciences de la Santé
University of Bamako
Universitat Tubingen
King Fahd University of Petroleum and Minerals
Wellcome Trust Research Laboratories Nairobi
National Institute of Allergy and Infectious Diseases
Texas Biomedical Research Institute
Nuffield Department of Clinical Medicine
Mahidol University
KEMRI/CDC Laboratories
Pennsylvania State University
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: Journal of Infectious Diseases. Vol.210, No.12 (2014), 1991-2000
Abstract: © The Author 2014. Background: Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation. Methods: We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection. Results. High genetic diversity (π = 2.4 × 10<sup>-4</sup>), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparison of the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drugresistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1. Conclusions: The sequence variations observed at drug-resistance loci reflect differences in each country's historical use of antimalarial drugs and may be useful in formulating local malaria treatment guidelines.
ISSN: 15376613
Appears in Collections:Scopus 2011-2015

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