A window size of 100 bp and a step size of 3 bp were used. B) Nucleotide diversity: Sliding window analysis showing nucleotide diversity (π values for (i) Pfama1 and (ii) Pvama1. Location of residues is indicated by the colored panel along the top of the chart: signal sequence (grey), DI (red), DII (orange), DIII (blue), transmembrane region (black).
vivax genes encoding the AMA1 ectodomain, with all polymorphisms including non-synonymous (NS SNP, red lines), synonymous (SP SNP, black lines) and singleton (dashed red and black lines, respectively) sites shown. vivax sequences A) Polymorphism: Schematic of the (i) P. The following results are based on the total dataset of 76 P. Polymorphism and selection of AMA1 genes in Plasmodium falciparum and Plasmodium vivax populations of Papua New Guinea. Differing patterns of selection on the AMA1 genes indicate that critical antigenic sites may differ between the species, highlighting the need for independent investigations of these two leading vaccine candidates. vivax, a finding that warrants further investigation. These results also suggest a smaller effective population size of P. falciparum AMA1 in this highly endemic area has important implications for development of AMA1-based vaccines in PNG and beyond. Higher diversity in the genes encoding P. vivax, and in both domains I and III for P. Balancing selection was detected only within domain I of AMA1 for P. falciparum (Madang = 12, Wosera = 20 Hd ≤0.92, R ≤45.8) than for P. vivax (Madang = 36, Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and recombination (R) was far lower for P. falciparum (Madang = 52 Wosera = 56) compared to P. vivax populations of Papua New Guinea (PNG), an area of similarly high prevalence (Pf = 22.3 to 38.8%, Pv = 15.3 to 31.8%).Ī total of 72 Pfama1 and 102 Pvama1 sequences were collected from two distinct areas, Madang and Wosera, on the highly endemic PNG north coast.ĭespite a greater number of polymorphic sites in the AMA1 genes of P. The aim of this study was to investigate the population genetics of leading malaria vaccine candidate AMA1 in sympatric P. Population genetic analyses can predict the effectiveness of interventions including vaccines, by providing insight into patterns of diversity and evolution. As Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed.
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