Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi

Handle URI:
http://hdl.handle.net/10754/622357
Title:
Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi
Authors:
Assefa, Samuel; Lim, Caeul; Preston, Mark D.; Duffy, Craig W.; Nair, Mridul; Adroub, Sabir; Kadir, Khamisah A.; Goldberg, Jonathan M.; Neafsey, Daniel E.; Divis, Paul; Clark, Taane G.; Duraisingh, Manoj T.; Conway, David J.; Pain, Arnab ( 0000-0002-1755-2819 ) ; Singh, Balbir
Abstract:
Malaria 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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Assefa 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.
Publisher:
Proceedings of the National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences
Issue Date:
6-Oct-2015
DOI:
10.1073/pnas.1509534112
PubMed ID:
26438871
PubMed Central ID:
PMC4620865
Type:
Article
ISSN:
0027-8424; 1091-6490
Sponsors:
We 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.
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAssefa, Samuelen
dc.contributor.authorLim, Caeulen
dc.contributor.authorPreston, Mark D.en
dc.contributor.authorDuffy, Craig W.en
dc.contributor.authorNair, Mridulen
dc.contributor.authorAdroub, Sabiren
dc.contributor.authorKadir, Khamisah A.en
dc.contributor.authorGoldberg, Jonathan M.en
dc.contributor.authorNeafsey, Daniel E.en
dc.contributor.authorDivis, Paulen
dc.contributor.authorClark, Taane G.en
dc.contributor.authorDuraisingh, Manoj T.en
dc.contributor.authorConway, David J.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorSingh, Balbiren
dc.date.accessioned2017-01-02T09:28:26Z-
dc.date.available2017-01-02T09:28:26Z-
dc.date.issued2015-10-06en
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.en
dc.identifier.issn0027-8424en
dc.identifier.issn1091-6490en
dc.identifier.pmid26438871en
dc.identifier.doi10.1073/pnas.1509534112en
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.en
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.en
dc.publisherProceedings of the National Academy of Sciencesen
dc.subjectAdaptationen
dc.subjectPlasmodium diversityen
dc.subjectPopulation genomicsen
dc.subjectReproductive isolationen
dc.subjectZoonosisen
dc.titlePopulation genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesien
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.identifier.pmcidPMC4620865en
dc.contributor.institutionPathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdomen
dc.contributor.institutionDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, United Statesen
dc.contributor.institutionMalaria Research Centre, Universiti Malaysia Sarawak, Kota Samarahan, Sarawak, 94300, Malaysiaen
dc.contributor.institutionBroad Institute of MIT and Harvard, Cambridge, MA, 02142, United Statesen
dc.contributor.institutionCenter for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Kita-ku, Sapporo, N20 W10, Japanen
kaust.authorNair, Mridulen
kaust.authorAdroub, Sabiren
kaust.authorPain, Arnaben
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