Abstract
Most malaria in Malaysia is caused by Plasmodium knowlesi parasites through zoonotic infection from macaque reservoir hosts. We obtained genome sequences from 28 clinical infections in Peninsular Malaysia to clarify the emerging parasite population structure and test for evidence of recent adaptation. The parasites all belonged to a major genetic population of P. knowlesi (cluster 3) with high genomewide divergence from populations occurring in Borneo (clusters 1 and 2). We also observed unexpected local genetic subdivision; most parasites belonged to 2 subpopulations sharing a high level of diversity except at particular genomic regions, the largest being a region of chromosome 12, which showed evidence of recent directional selection. Surprisingly, we observed a third subpopulation comprising P. knowlesi infections that were almost identical to each other throughout much of the genome, indicating separately maintained transmission and recent genetic isolation. Each subpopulation could evolve and present a broader health challenge in Asia.
Highlights
Most malaria in Malaysia is caused by Plasmodium knowlesi parasites through zoonotic infection from macaque reservoir hosts
The tree showed that all of the 28 samples from Peninsular Malaysia belonged to a genetic population divergent from those in Malaysian Borneo
These new clinical samples from Peninsular Malaysia clustered with the old laboratory isolates that were sequenced previously and had initially indicated the existence of a third major genetic population within this species [15]
Summary
Most malaria in Malaysia is caused by Plasmodium knowlesi parasites through zoonotic infection from macaque reservoir hosts. Zoonotic malaria was considered to be very rare, but original findings in Malaysia [5,6] and subsequent surveys elsewhere have revealed that many human malaria cases in Southeast Asia are caused by the macaque parasite Plasmodium knowlesi [7] This parasite species causes almost all malaria in Malaysia [4] and is responsible for clinical cases throughout Southeast Asia, where the distributions of macaque reservoir hosts and mosquito vectors overlap with human populations [8]. The short-term adaptability of this single strain is further illustrated by selection for culture in long-tailed macaque erythrocytes, which was associated with the loss of a specific ligand gene needed for invading human erythrocytes [21] These examples from laboratory observations strongly suggest that highly diverse natural parasite populations are likely to adapt to changing conditions. To determine the population genetic substructure within P. knowlesi locally, we analyzed recent clinical samples from patients with P. knowlesi infection in Peninsular Malaysia by using wholegenome sequencing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
