Population genomic structure and adaptation in the zoonotic malaria parasitePlasmodium knowlesi

Malaria cases caused by the zoonotic parasitePlasmodium knowlesiare 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 diversit...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2015-10, Vol.112 (42), p.13027-13032
Hauptverfasser: Assefa, Samuel, Lim, Caeul, Preston, Mark D., Duffy, Craig W., Nair, Mridul B., Adroub, Sabir A., Kadir, Khamisah A., Goldberg, Jonathan M., Neafsey, Daniel E., Divis, Paul, Clark, Taane G., Duraisingh, Manoj T., Conway, David J., Pain, Arnab, Singh, Balbir
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Sprache:eng
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Zusammenfassung:Malaria cases caused by the zoonotic parasitePlasmodium knowlesiare 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 × 10−3) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite speciesPlasmodium falciparumandPlasmodium vivax. A remarkable substructure is revealed withinP. 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 ST) = 0.21, with 9,293 SNPs having fixed differences ofF ST= 1.0]. This differentiation showed marked heterogeneity across the genome, with meanF STvalues 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.
ISSN:0027-8424
1091-6490