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. Author summary Plasmodium knowlesi , a common malaria parasite of long-tailed and pig-tailed macaques, is now recognized as a significant cause of human malaria, accounting for up to 70% of malaria cases in certain areas in Southeast Asia including Malaysian Borneo. Rapid human population growth, deforestation and encroachment on wild macaque habitats potentially increase contact with humans and drive up the prevalence of human Plasmodium knowlesi infections. Appropriate molecular tools and sampling are needed to assist surveillance by malaria control programmes, and to understand the genetics underpinning Plasmodium knowlesi transmission and switching of hosts from macaques to humans. We report a comprehensive analysis of the largest assembled set of Plasmodium knowlesi genome sequences from Malaysia. It reveals genetic regions that have been recently exchanged between long-tailed and pig-tailed macaques, which contain genes with signals indicative of rapid contemporary ecological change, including deforestation. Additional analyses partition Plasmodium knowlesi infections in Borneo into 3 deeply branched lineages of ancient origin, which founded the two divergent populations associated with long-tailed and pig-tailed macaques and a third, highly diverse population, on the Peninsular mainland. Overall, the complex Plasmodium parasite evolution observed and likelihood of further host transitions are potential challenges to malaria control in Malaysia.
【초록키워드】 Evolution, Human, Genome, Genetic, Infection, Transmission, parasites, Malaysia, genetics, Population, malaria, Asia, Prevalence, Protein, Region, infections, Surveillance, humans, Lineage, Isolation, Rapid, sampling, macaque, molecular, genotypes, genomic, lineages, macaques, Evidence, Interaction, genome sequence, Contact, Disruption, switching, evidence of, human population, contact with, malaria control, population growth, chromosome, stages, comprehensive analysis, growth, complex, human infection, traits, hosts, organelle, Plasmodium, subpopulations, reference genome, deforestation, subpopulation, parasite, nuclear, infecting, Host, isolate, likelihood, selected, resulting, described, expressed, analysis, reveal, expected, genes encoding, assist, ecological, Appropriate, 【제목키워드】 Human, Genome, Recombination, subpopulation, nuclear, reveal,