Distinct patterns of diversity, population structure and evolution in the AMA1 genes of sympatric Plasmodium falciparum and Plasmodium vivax populations of Papua New Guinea from an area of similarly high transmission

Abstract

BackgroundAs 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. Population genetic analyses can predict the effectiveness of interventions including vaccines, by providing insight into patterns of diversity and evolution. The aim of this study was to investigate the population genetics of leading malaria vaccine candidate AMA1 in sympatric P. falciparum and 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%).MethodsA total of 72 Pfama1 and 102 Pvama1 sequences were collected from two distinct areas, Madang and Wosera, on the highly endemic PNG north coast.ResultsDespite a greater number of polymorphic sites in the AMA1 genes of P. falciparum (Madang = 52; Wosera = 56) compared to P. vivax (Madang = 36, Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and recombination (R) was far lower for P. falciparum (Madang = 12, Wosera = 20; Hd ≤0.92, R ≤45.8) than for P. vivax (Madang = 50, Wosera = 38; Hd = 0.99, R = ≤70.9). Balancing selection was detected only within domain I of AMA1 for P. vivax, and in both domains I and III for P. falciparum.ConclusionsHigher diversity in the genes encoding P. vivax AMA1 than in P. falciparum AMA1 in this highly endemic area has important implications for development of AMA1-based vaccines in PNG and beyond. These results also suggest a smaller effective population size of P. falciparum compared to P. vivax, a finding that warrants further investigation. 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.

Genetic diversity of the Plasmodium falciparum apical membrane antigen I gene in parasite population from the China–Myanmar border area

“…A minimum of 16 recombination events were detected in the China-Myanmar border and in Thai samples (Polley et al, 2003), compared to over 20 recombinant events detected in Papua New Guinea (Arnott et al, 2014) and African populations (Osier et al, 2010; Polley and Conway, 2001; Takala et al, 2009; Tetteh et al, 2009) (Table 2). The recombination parameter ( C ) between adjacent nucleotide sites and for the whole sequence had a value of 0.003 and 3.8, respectively in the China-Myanmar border population.…”

“…A total of 956 publically available PfAMA1 sequences representing seven P. falciparum populations were retrieved from GenBank: Thailand (Polley et al, 2003), Papua New Guinea (Arnott et al, 2014), Gambia (Tetteh et al, 2009), Nigeria (Polley and Conway, 2001), Kenya (Osier et al, 2010), Mali (Takala et al, 2009), and Venezuela (Ord et al, 2008). Analysis of the minimum number of recombination events ( R M ) (Hudson and Kaplan, 1985), recombination parameter C ( C = 4 Nr , where N is the effective population size and r is the probability of recombination between adjacent nucleotides per generation) (Hudson, 1987), as well as linkage disequilibrium (LD) using the indices D ’ (Lewontin, 1964) and R 2 (Hill and Robertson, 1968) were calculated by DnaSP (Librado and Rozas, 2009).…”

Higher Complexity of Infection and Genetic Diversity of Plasmodium vivax Than Plasmodium falciparum across all Malaria Transmission Zones of Papua New Guinea

“…33,[50][51][52] The complexity of infection was somewhat variable among different regions and geographic clusters for both species, and is comparable to that found in a wide range of higher transmission settings in other countries. 27,28,33,38,[53][54][55][56][57] However, the vast majority of P. vivax infections were polyclonal and MOI was almost 2-fold higher than that of P. falciparum. Furthermore, although complexity of infection was associated with prevalence for P. falciparum, there was no association between these parameters for P. vivax.…”

“…Previous studies in PNG have focused on the highest transmission region on the north coast of PNG, namely the East Sepik and Madang Province. [38][39][40][41][42] Therefore, we aimed to gather genotyping data from all areas covered in the national malaria indicator survey mentioned earlier. Using this data, we have compared the molecular epidemiology of P. vivax and P. falciparum populations from all malaria-endemic areas of PNG representing a range of transmission intensities.…”

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

“…Studies of microsatellites and highly variable antigens of sympatric P. vivax and P. falciparum populations in Southeast Asia and the Southwest Pacific have consistently shown P. vivax populations to be more diverse, with a higher effective population size (N eff ), more stable transmission, and increased gene flow between geographic islands, whereas P. falciparum populations tend to be clonal with episodic transmission and structure-by-geography (10)(11)(12)(13)(14)(15). We hypothesized that the species have evolved disparate responses to selective pressures and that genomic studies of sympatric Plasmodium sp.…”