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dc.contributor.authorAssefa, Samuel
dc.contributor.authorLim, Caeul
dc.contributor.authorPreston, Mark D.
dc.contributor.authorDuffy, Craig W.
dc.contributor.authorNair, Mridul
dc.contributor.authorAdroub, Sabir
dc.contributor.authorKadir, Khamisah A.
dc.contributor.authorGoldberg, Jonathan M.
dc.contributor.authorNeafsey, Daniel E.
dc.contributor.authorDivis, Paul
dc.contributor.authorClark, Taane G.
dc.contributor.authorDuraisingh, Manoj T.
dc.contributor.authorConway, David J.
dc.contributor.authorPain, Arnab
dc.contributor.authorSingh, Balbir
dc.date.accessioned2017-01-02T09:28:26Z
dc.date.available2017-01-02T09:28:26Z
dc.date.issued2015-10-05
dc.identifier.citationAssefa S, Lim C, Preston MD, Duffy CW, Nair MB, et al. (2015) Population genomic structure and adaptation in the zoonotic malaria parasitePlasmodium knowlesi. Proceedings of the National Academy of Sciences 112: 13027–13032. Available: http://dx.doi.org/10.1073/pnas.1509534112.
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.pmid26438871
dc.identifier.doi10.1073/pnas.1509534112
dc.identifier.urihttp://hdl.handle.net/10754/622357
dc.description.abstractMalaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (F) = 0.21, with 9,293 SNPs having fixed differences of F = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean F values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
dc.description.sponsorshipWe thank all patients, nurses, doctors, and laboratory technicians at Kapit and Betong Hospitals and core staff in our research institutes for their assistance; Hifzur Rahman Ansari (King Abdullah University of Science and Technology) for submission of the sequences to European Nucleotide Archive; the Malaria Research and Reference Reagent Resource Center for providing the P. knowlesi strains contributed by William E. Collins; and the Director General of Health in Malaysia for permission to publish this paper. This study was supported by Universiti Malaysia Sarawak Grants E14054/F05/54PK1/09/2012(01) and 01(TD03)/1003/2013(01); UK Medical Research Council Grants MRC G1100123, MR/K000551/1, and MR/M01360X/1; European Research Council Advanced Award AdG-2011-294428; NIH Grant 5R01AI091787; Bill and Melinda Gates Foundation Grant OPP1023594; a postgraduate scholarship from the Ministry of Education in Malaysia; and faculty baseline funding from King Abdullah University of Science and Technology.
dc.publisherProceedings of the National Academy of Sciences
dc.subjectAdaptation
dc.subjectPlasmodium diversity
dc.subjectPopulation genomics
dc.subjectReproductive isolation
dc.subjectZoonosis
dc.titlePopulation genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.identifier.journalProceedings of the National Academy of Sciences
dc.identifier.pmcidPMC4620865
dc.contributor.institutionPathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom
dc.contributor.institutionDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, United States
dc.contributor.institutionMalaria Research Centre, Universiti Malaysia Sarawak, Kota Samarahan, Sarawak, 94300, Malaysia
dc.contributor.institutionBroad Institute of MIT and Harvard, Cambridge, MA, 02142, United States
dc.contributor.institutionCenter for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Kita-ku, Sapporo, N20 W10, Japan
kaust.personNair, Mridul
kaust.personAdroub, Sabir
kaust.personPain, Arnab
dc.date.published-online2015-10-05
dc.date.published-print2015-10-20


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