Abstract
The macaque parasite Plasmodium knowlesi is a significant concern in Malaysia where cases of human infection are increasing. Parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (Macaca fascicularis (Mf)) or pig-tailed macaques (Macaca nemestrina (Mn)). We used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from Malaysian-Borneo and Peninsular-Malaysia. Nuclear genomes were dimorphic, as expected, but new evidence of chromosomal-segment exchanges between subpopulations was found. A large segment on chromosome 8 originating from the Mn subpopulation and containing genes encoding proteins expressed in mosquito-borne parasite stages, was found in Mf genotypes. By contrast, non-recombining organelle genomes partitioned into 3 deeply branched lineages, unlinked with nuclear genomic dimorphism. Subpopulations which diverged in isolation have re-connected, possibly due to deforestation and disruption of wild macaque habitats. The resulting genomic mosaics reveal traits selected by host-vector-parasite interactions in a setting of ecological transition.
Highlights
Plasmodium knowlesi, a common malaria parasite of long-tailed Macaca fascicularis (Mf) and pig-tailed M. nemestrina (Mn) macaques in Southeast Asia, is recognized as a significant cause of human malaria
Genomic diversity of Plasmodium knowlesi jointly funded by the UK MRC and UK Department for International Development
A cluster of human P. knowlesi cases were reported from Malaysian Borneo in 2004 [1], but human infections are known to be widespread in Southeast Asia [2,3], and have been reported in travellers from outside the region [2,4]
Summary
Plasmodium knowlesi, a common malaria parasite of long-tailed Macaca fascicularis (Mf) and pig-tailed M. nemestrina (Mn) macaques in Southeast Asia, is recognized as a significant cause of human malaria. A cluster of human P. knowlesi cases were reported from Malaysian Borneo in 2004 [1], but human infections are known to be widespread in Southeast Asia [2,3], and have been reported in travellers from outside the region [2,4]. Whole genome-level genetic diversity among P. knowlesi from human infections in Sarikei in Sarawak demonstrates substantial dimorphism extending over at least 50% of the genome [9]. This finding is supported by analysis of microsatellite diversity in parasites from Mf, Mn and human infections across Peninsular and Borneo Malaysia [10]. A third genome cluster has been described from geographically distinct Peninsular Malaysia [11, 12, 13, 14]
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