Whole genome sequencing of amplified Plasmodium knowlesi DNA from unprocessed blood reveals genetic exchange events between Malaysian Peninsular and Borneo subpopulations

Ernest Diez Benavente, Ana Rita Gomes, Jeremy Ryan De Silva, Matthew Grigg, Harriet Walker, Bridget E. Barber, Timothy William, Tsin Wen Yeo, Paola Florez de Sessions, Abhinay Ramaprasad, Amy Ibrahim, James Charleston, Martin L. Hibberd, Arnab Pain, Robert W. Moon, Sarah Auburn, Lau Yee Ling, Nicholas M. Anstey, Taane G. Clark, Susana Campino

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21 Scopus citations


The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.
Original languageEnglish (US)
JournalScientific Reports
Issue number1
StatePublished - Jul 8 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): BAS/1/1020-01-01
Acknowledgements: We thank Don Van Schalkwyk for providing biological materials from the P. knowlesi reference strain. We thank
the KAUST Bioscience Core Lab (BCL) facility for sequencing the unamplifed isolates. AI is funded by a UK
Medical Research Council LiD PhD studentship. RWM is supported by an MRC Career Development Award
(MR/M021157/1) jointly funded by the UK Medical Research Council and UK Department for International
Development. TGC is funded by the Medical Research Council UK (Grant No. MR/M01360X/1, MR/N010469/1,
MR/R025576/1, and MR/R020973/1) and BBSRC (Grant No. BB/R013063/1). SC is funded by Medical Research
Council UK grants (MR/M01360X/1, MR/R025576/1, and MR/R020973/1) and BBSRC (Grant no. BB/
R013063/1). Te Sabah studies were funded by the Malaysian Ministry of Health (grant number BP00500420)
and the Australian National Health and Medical Research Council (grant numbers 1037304, 1132975 and
1045156) and fellowships (1042072 and 1135820 to NMA, 1088738 to BEB, and 1138860 to MJG). AP and AR
are supported by a faculty baseline fund (BAS/1/1020-01-01) to AP. We gratefully acknowledge the Scientifc
Computing Group for data management and compute infrastructure at Genome Institute of Singapore for their
help. Te MRC eMedLab computing resource was used for bioinformatics and statistical analysis.


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