Genomic epidemiology of Plasmodium knowlesi reveals putative genetic drivers of adaptation in Malaysia
Sabah, Malaysia, has amongst the highest burden of human Plasmodium knowlesi infection in the world, associated with increasing encroachment on the parasite's macaque host habitat. However, the genomic make-up of P. knowlesi in Sabah was previously poorly understood. To inform on local patterns of transmission and putative adaptive drivers, we conduct population-level genetic analyses of P. knowlesi human infections using 52 new whole genomes from Sabah, Malaysia, in combination with publicly available data. We identify the emergence of distinct geographical subpopulations within the macaque-associated clusters using identity-by-descent-based connectivity analysis. Secondly, we report on introgression events between the clusters, which may be linked to differentiation of the subpopulations, and that overlap genes critical for survival in human and mosquito hosts. Using village-level locations from P. knowlesi infections, we also identify associations between several introgressed regions and both intact forest perimeter-area ratio and mosquito vector habitat suitability. Our findings provide further evidence of the complex role of changing ecosystems and sympatric macaque hosts in Malaysia driving distinct genetic changes seen in P. knowlesi populations. Future expanded analyses of evolving P. knowlesi genetics and environmental drivers of transmission will be important to guide public health surveillance and control strategies.
Authors
- Edwin Sutanto (ORCID: https://orcid.org/0000-0002-2997-4648)
- Angelica F. Tan (ORCID: https://orcid.org/0000-0001-7914-758X)
- Giri Shan Rajahram (ORCID: https://orcid.org/0000-0002-8123-476X)
- Zbynek Bozdech (ORCID: https://orcid.org/0000-0002-9830-8446)
- Sarah Auburn (ORCID: https://orcid.org/0000-0002-4638-536X)
- Nicolas Aranciaga (ORCID: https://orcid.org/0000-0002-3120-5768)
- Matthew A. Field (ORCID: https://orcid.org/0000-0003-0788-6513)
- CHRIS J. DRAKELEY (ORCID: https://orcid.org/0000-0003-4863-075X)
- Timothy William (ORCID: https://orcid.org/0000-0002-2195-6736)
- Matthew J. Grigg (ORCID: https://orcid.org/0000-0001-9914-8352)
- Bridget E. Barber (ORCID: https://orcid.org/0000-0003-1066-7960)
- Jenarun Jelip
- Ernest Diez Benavente (ORCID: https://orcid.org/0000-0002-4313-4290)
- Michal Kucharski (ORCID: https://orcid.org/0000-0002-1505-5608)
- Jacob A. F. Westaway (ORCID: https://orcid.org/0000-0002-5171-819X)
- Kim A. Piera (ORCID: https://orcid.org/0000-0002-7414-9604)
- Danshy A. Alaza
- Roberto Amato (ORCID: https://orcid.org/0000-0001-8633-9221)
- Kamil A. Braima (ORCID: https://orcid.org/0000-0003-2529-2313)
- Sourav Nayak (ORCID: https://orcid.org/0000-0002-7659-5712)
- Hidayat Trimarsanto (ORCID: https://orcid.org/0000-0003-2436-8283)
- Nicholas M. Anstey
Institutions
- Ministry of Health (MY)
- Garvan Institute of Medical Research (AU)
- Universiti of Malaysia Sabah (MY)
- Nanyang Technological University (SG)
- Eijkman Institute for Molecular Biology (ID)
- Australian Institute of Tropical Health and Medicine (AU)
- Wellcome Sanger Institute (GB)
- Charles Darwin University (AU)
- University Medical Center Utrecht (NL)
- Menzies School of Health Research (AU)
- London School of Hygiene & Tropical Medicine (GB)
- Sabah Environmental Trust (MY)
- National Research and Innovation Agency (ID)
- James Cook University (AU)
Publication Details
- Journal
- PLoS neglected tropical diseases
- Published
- 2025-03-12
- DOI
- https://doi.org/10.1371/journal.pntd.0012885
- Citations
- 1
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- Ministry of Education
- Department of Foreign Affairs and Trade, Australian Government
- Kementerian Kesihatan Malaysia
- National Institutes of Health
- National Health and Medical Research Council
- Medical Research Foundation