Genetic polymorphism and natural selection of apical membrane antigen-1 in Plasmodium malariae isolated from Vietnam

BACKGROUND: Plasmodium malariae, a causative agent of human quartan malaria, has been largely overlooked due to its mild clinical manifestations and low prevalence. Genetic information of the parasite is also very limited, particularly for clinical isolates. In this study, we analyzed the genetic nature of apical membrane antigen-1 (AMA-1) in Vietnam P. malariae isolates to expand knowledge on the genetic nature of the vaccine candidate protein. METHOD: The gene encoding AMA-1 of P. malariae (pmama-1) was amplified from 95 Vietnam P. malariae isolates and sequenced. Polymorphic patterns and natural selection of the pmama-1 were examined with programs such as BioEdit, MEGA4, and DnaSP. Comparative analysis of genetic polymorphisms and natural selection in pmama-1 from other Southeast Asia countries was also conducted. RESULTS: A total of 117 Vietnam pmama-1 sequences were obtained from 95 Vietnam P. malariae isolates. The majority of amino acid polymorphisms were identified in domains I and II, grouping Vietnam pmama-1 into 19 distinct haplotypes. Although overall profiles of amino acid polymorphisms in Vietnam pmama-1 mirrored those from other Southeast Asia countries, positions and frequencies of amino acid changes varied by countries. Most amino acid changes detected in pmama-1 were predicted to be positioned on the surface of the protein. Evidences of natural selection and evolutionary trend of the gene were also observed. CONCLUSIONS: This study highlights a substantial genetic heterogeneity of pmama-1 in P. malariae population and expands our knowledge on genetic nature of this gene. To understand the genetic nature and evolution of global pmama-1, further studies with larger numbers of P. malariae isolates from other global regions are necessary.