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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/40904
Title: Population structure shapes copy number variation in malaria parasites
Authors: Ian H. Cheeseman
Becky Miller
John C. Tan
Asako Tan
Shalini Nair
Standwell C. Nkhoma
Marcos De Donato
Hectorina Rodulfo
Arjen Dondorp
Oralee H. Branch
Lastenia Ruiz Mesia
Paul Newton
Mayfong Mayxay
Alfred Amambua-Ngwa
David J. Conway
François Nosten
Michael T. Ferdig
Tim J.C. Anderson
Texas Biomedical Research Institute
University of Notre Dame
University of Malawi College of Medicine
Universidad de Oriente - Venezuela
Mahidol University
Nuffield Department of Clinical Medicine
New York University
Universidad Nacional de la Amazonia Peruana, Iquitos
Mahosot Hospital
University of Health Sciences
Medical Research Council Laboratories Gambia
London School of Hygiene & Tropical Medicine
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Mar-2016
Citation: Molecular Biology and Evolution. Vol.33, No.3 (2016), 603-620
Abstract: © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84964494870&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/40904
ISSN: 15371719
07374038
Appears in Collections:Scopus 2016-2017

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