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.

Genome‐wide mosaicism in divergence between zoonotic malaria parasite subpopulations with separate sympatric transmission cycles

“…A separate simultaneous study reported data from another six infections, confirming the divergence between sympatric subpopulations (Pinheiro et al., ), but this did not cumulatively give a much deeper sample. In agreement with the initial study (Assefa et al., ), a recent secondary analysis of the previously published data confirmed the existence of genomic regions with shared polymorphisms (Diez Benavente et al., ), but did not include any new data.…”

“…The recombinant genomes that are now circulating offer a great diversity on which selection may operate, but there is no evidence yet of specific adaptation at introgressed loci. A recent re‐analysis of previously published data identified a common shared haplotype in a chromosomal region with low divergence between the subpopulations (Diez Benavente et al., ), although an observation that the region had a slightly higher than background proportion of genes predicted to be expressed at a particular developmental stage may not be relevant, as an extended haplotype may result from selection on a single locus rather than on multiple genes.…”

Genetic diversity and natural selection of Plasmodium knowlesi merozoite surface protein 1 paralog gene in Malaysia

“…Results were significant with robust Bayesian structure analysis where 4 different sub-populations were identified however, higher sample number are required from Sarikei and Peninsular Malaysia for accurate determination of the population structure. A recent genomic study identified host-specific sub-populations of P. knowlesi infections and has indicated a recombination event in the sexual stages of the parasite [ 49 ]. These observations might indicate that humans are susceptible to infection by any of the P. knowlesi populations circulating in these regions.…”

Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development

“…A principal component analysis (not shown) based on pairwise SNP differences between isolates did not reveal any geographic outliers. We used the proportion of heterozygous calls per sample (>0.015%) as well as the fraction of genome indicating Multiplicity Of Infection (MOI)>1 obtained using estMOI (>30%) 34 as described previously 35 to remove samples with MOI>1 ( S3 Fig. ).…”