Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 among Plasmodium vivax Korean isolates

Abstract

Background: The carboxy-terminal 42 kDa region of Plasmodium vivax merozoite surface protein-1 (PvMSP-1(42)) is a leading candidate antigen for blood stage vaccine development. However, this region has been observed to be highly polymorphic among filed isolates of P. vivax. Therefore it is important to analyse the existing diversity of this antigen in the field isolates of P. vivax. In this study, the genetic diversity and natural selection in PvMSP-1(42) among P. vivax Korean isolates were analysed. Methods: A total of 149 P. vivax-infected blood samples collected from patients in Korea were used. The region flanking PvMSP-1(42) was amplified by PCR, cloned into Escherichia coli, and then sequenced. The polymorphic characteristic and natural selection of PvMSP-1(42) were analysed using the DNASTAR, MEGA4 and DnaSP programs. Results: A total of 11 distinct haplotypes of PvMSP-1(42) with 40 amino acid changes, as compared to the reference Sal I sequence, were identified in the Korean P. vivax isolates. Most of the mutations were concentrated in the 33 kDa fragment (PvMSP-1(33)), but a novel mutation was found in the 19 kDa fragment (PvMSP-1(19)). PvMSP-1(42) of Korean isolates appeared to be under balancing selection. Recombination may also play a role in the resulting genetic diversity of PvMSP-1(42). Conclusions: PvMSP-1(42) of Korean P. vivax isolates displayed allelic polymorphisms caused by mutation, recombination and balancing selection. These results will be useful for understanding the nature of the P. vivax population in Korea and for development of a PvMSP-1(42) based vaccine against P. vivax.