Genetic diversity of merozoite surface protein-1 C-terminal 42 kDa of Plasmodium falciparum (PfMSP-1) may be greater than previously known in global isolates.

Background: The C-terminal 42 kDa region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1) is the target of an immune response. It has been recognised as one of the promising candidate antigens for a blood-stage malaria vaccine. Genetic structure of PfMSP-1 has been considered to be largely conserved in the P. falciparum population. However, only limited information is currently available. This study aimed to analyse genetic diversity and the effect of natural selection on PfMSP-1 among the Myanmar P. falciparum population and compare them with publicly available PfMSP-1 from global P. falciparum populations.

Methods: A total of 69 P. falciparum clinical isolates collected from Myanmar malaria patients in Upper Myanmar in 2015 were used. The PfMSP-1 region was amplified by polymerase chain reaction, cloned and sequenced. Genetic structure and natural selection of this region were analysed using MEGA4 and DnaSP programs. Polymorphic nature and natural selection in global PfMSP-1 were also investigated.

Results: All three allele types (MAD20, K1, and RO33) of PfMSP-1 were identified in Myanmar isolates of P. falciparum. Myanmar PfMSP-1 displayed genetic diversity. Most polymorphisms were scattered in blocks 16 and 17. Polymorphisms observed in Myanmar PfMSP-1 showed a similar pattern to those of global PfMSP-1; however, they were not identical to each other. Genetic diversity of Myanmar PfMSP-1 was relatively lower than that of PfMSP-1 from different geographical regions. Evidence of natural selection and recombination were found. Comparative analysis of genetic polymorphism and natural selection in the global PfMSP-1 population suggested that this region was not tightly conserved in global PfMSP-1 as previously thought and is under the complicated influence of natural selection and recombination.

Conclusions: Global PfMSP-1 revealed limited, but non-negligible, genetic diversity by allele types and geographical origins. Complicated natural selection and potential recombination might have occurred in global PfMSP-1. Comprehensive monitoring of genetic diversity for global PfMSP-1 would be needed to better understand the polymorphic nature and evolutionary aspect of PfMSP-1 in the global P. falciparum population. More thought would be necessary for designing a vaccine based on PfMSP-1.