title: Phylogeography of var gene repertoires reveals fine-scale geospatial clustering of Plasmodium falciparum populations in a highly endemic area.
abstract: Plasmodium falciparum malaria is a major global health problem that is being targeted for progressive elimination. Knowledge of local disease transmission patterns in endemic countries is critical to these elimination efforts. To investigate fine-scale patterns of malaria transmission, we have compared repertoires of rapidly evolving var genes in a highly endemic area. A total of 3680 high-quality DBLα-sequences were obtained from 68 P. falciparum isolates from ten villages spread over two distinct catchment areas on the north coast of Papua New Guinea (PNG). Modelling of the extent of var gene diversity in the two parasite populations predicts more than twice as many var gene alleles circulating within each catchment (Mugil = 906; Wosera = 1094) than previously recognized in PNG (Amele = 369). In addition, there were limited levels of var gene sharing between populations, consistent with local parasite population structure. Phylogeographic analyses demonstrate that while neutrally evolving microsatellite markers identified population structure only at the catchment level, var gene repertoires reveal further fine-scale geospatial clustering of parasite isolates. The clustering of parasite isolates by village in Mugil, but not in Wosera was consistent with the physical and cultural isolation of the human populations in the two catchments. The study highlights the microheterogeneity of P. falciparum transmission in highly endemic areas and demonstrates the potential of var genes as markers of local patterns of parasite population structure.
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute, 3052, Melbourne, Vic., Australia; Department of Medical Biology, University of Melbourne, 3052, Melbourne, Vic., Australia.
authors.forename: Sofonias K
authors.initials: SK
authors.lastname: Tessema
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Monk
authors.forename: Mark B
authors.initials: MB
authors.lastname: Schultz
authors.forename: Livingstone
authors.initials: L
authors.lastname: Tavul
authors.forename: John C
authors.initials: JC
authors.lastname: Reeder
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Barry
mesh_terms: D000483:Alleles; D016000:Cluster Analysis; D016054:DNA, Protozoan / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population; D016778:Malaria, Falciparum / Q000469:parasitology; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010219:Papua New Guinea; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum
keywords: DBLα; Plasmodium falciparum; genetic diversity; immune evasion; population structure; var genes