Analysis of nuclear and organellar genomes of Plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations

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.

Citation
Diez Benavente E, Florez de Sessions P, Moon RW, Holder AA, Blackman MJ, et al. (2017) Analysis of nuclear and organellar genomes of Plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations. PLOS Genetics 13: e1007008. Available: http://dx.doi.org/10.1371/journal.pgen.1007008.

Acknowledgements
TGC is funded by the Medical Research Council UK (Grant no. MR/K000551/1, MR/M01360X/1, MR/N010469/1, MC_PC_15103). SC and CR are funded by the Medical Research Council UK (Grant no. MR/M01360X/1). RWM is supported by an MRC Career Development Award jointly funded by the UK MRC and UK Department for International Development. This work was supported in part by the Francis Crick Institute that receives its core funding from Cancer Research UK (FC001097, FC001043), the UK Medical Research Council (FC001097, FC001043), and the Wellcome Trust (FC001097, FC001043). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher
Public Library of Science (PLoS)

Journal
PLOS Genetics

DOI
10.1371/journal.pgen.1007008

PubMed ID
28922357

Additional Links
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007008

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