Abstract
Plasmodium knowlesi is a significant cause of human malaria transmitted as a zoonosis from macaque reservoir hosts in South‐East Asia. Microsatellite genotyping has indicated that human infections in Malaysian Borneo are an admixture of two highly divergent sympatric parasite subpopulations that are, respectively, associated with long‐tailed macaques (Cluster 1) and pig‐tailed macaques (Cluster 2). Whole‐genome sequences of clinical isolates subsequently confirmed the separate clusters, although fewer of the less common Cluster 2 type were sequenced. Here, to analyse population structure and genomic divergence in subpopulation samples of comparable depth, genome sequences were generated from 21 new clinical infections identified as Cluster 2 by microsatellite analysis, yielding a cumulative sample size for this subpopulation similar to that for Cluster 1. Profound heterogeneity in the level of intercluster divergence was distributed across the genome, with long contiguous chromosomal blocks having high or low divergence. Different mitochondrial genome clades were associated with the two major subpopulations, but limited exchange of haplotypes from one to the other was evident, as was also the case for the maternally inherited apicoplast genome. These findings indicate deep divergence of the two sympatric P. knowlesi subpopulations, with introgression likely to have occurred recently. There is no evidence yet of specific adaptation at any introgressed locus, but the recombinant mosaic types offer enhanced diversity on which selection may operate in a currently changing landscape and human environment. Loci responsible for maintaining genetic isolation of the sympatric subpopulations need to be identified in the chromosomal regions showing fixed differences.
Highlights
The zoonotic malaria parasite Plasmodium knowlesi is a significant cause of human malaria in Southeast Asia
Microsatellite genotyping has indicated that human infections in Malaysian Borneo are an admixture of two highly divergent sympatric parasite subpopulations that are respectively associated with long-tailed macaques (Cluster 1) and pig-tailed macaques (Cluster 2)
Different mitochondrial genome clades were associated with the two major subpopulations, but limited exchange of haplotypes from one to the other was evident, as was the case for the maternally-inherited apicoplast genome. These findings indicate deep divergence of the two sympatric P. knowlesi subpopulations, with introgression likely to have occurred recently
Summary
The zoonotic malaria parasite Plasmodium knowlesi is a significant cause of human malaria in Southeast Asia. Multi-locus microsatellite genotyping analysis of P. knowlesi infections revealed that human infections in Malaysian Borneo comprise two major genetic subpopulations that are respectively associated with long-tailed and pig-tailed macaque reservoir hosts (Divis et al, 2015), with significant divergence confirmed by whole-genome sequence analyses of parasites in human infections (Assefa et al, 2015). Further analyses of additional samples has subsequently revealed a third divergent subpopulation of P. knowlesi (Cluster 3) on the mainland of Southeast Asia which includes Peninsular Malaysia (Divis et al, 2017; Yusof et al, 2016). To develop laboratory studies on the other two major zoonotic populations will require establishment of parasite isolates in controlled monkey infections, or ideally into culture with erythrocytes. Isolation of new P. knowlesi samples from human clinical infections is relatively straightforward, as most of these are not mixed with other species, whereas most natural P. knowlesi infections in macaques occur together with other primate malaria parasite species (Lee et al, 2011)
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