Publication: Population structure shapes copy number variation in malaria parasites
Issued Date
2016-03-01
Resource Type
ISSN
15371719
07374038
07374038
Other identifier(s)
2-s2.0-84964494870
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Biology and Evolution. Vol.33, No.3 (2016), 603-620
Suggested Citation
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 Population structure shapes copy number variation in malaria parasites. Molecular Biology and Evolution. Vol.33, No.3 (2016), 603-620. doi:10.1093/molbev/msv282 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/40904
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Population structure shapes copy number variation in malaria parasites
Other Contributor(s)
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
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
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.
