Genetic diversity of the full length apical membrane antigen-1 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Plasmodium knowlesi is a simian malaria parasite that causes significant zoonotic infections in Southeast Asia, particularly in Malaysia. The Plasmodium thrombospondin-related apical merozoite protein (TRAMP) plays an essential role in the invasion of the parasite into its host erythrocyte. The present study investigated the genetic polymorphism and natural selection of the full length PkTRAMP from P. knowlesi clinical isolates from Malaysia. Blood samples (n = 40) were collected from P. knowlesi malaria patients from Peninsular Malaysia and Malaysian Borneo. The PkTRAMP gene was amplified using PCR, followed by cloning into a plasmid vector and sequenced. Results showed that the nucleotide diversity of PkTRAMP was low (π: 0.009). Z-test results indicated negative (purifying) selection of PkTRAMP. The alignment of the deduced amino acid sequences of PkTRAMP of Peninsular Malaysia and Malaysian Borneo revealed 38 dimorphic sites. A total of 27 haplotypes were identified from the amino acid sequence alignment. Haplotype analysis revealed that there was no clustering of PkTRAMP from Peninsular Malaysia and Malaysian Borneo.

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Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia

Lau

Hamid

et al. 2022

Parasitol Res

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Genetic diversity and in silico analysis of Plasmodium knowlesi Serine Repeat Antigen (SERA) 3 antigen 2 in Malaysia

Tan

Ding

Fong

et al. 2023

Infection, Genetics and Evolution

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Natural selection on apical membrane antigen 1 (AMA1) of an emerging zoonotic malaria parasite Plasmodium inui

Putaporntip,

Kuamsab,

Jongwutiwes

2024

Sci Rep

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Apical membrane antigen 1 (AMA1) of malaria parasites plays an important role in host cell invasion. Antibodies to AMA1 can inhibit malaria merozoite invasion of erythrocytes while vaccine-induced specific cytotoxic T cell responses to this protein are associated with clinical protection. Polymorphisms in AMA1 of Plasmodium falciparum (PfAMA1) and P. vivax (PvAMA1) are of concern for vaccine development. To date, little is known about sequence diversity in ama1 of P. inui ( Piama1 ), an emerging zoonotic malaria parasite. In this study, 80 complete Piama1 coding sequences were obtained from 57 macaques in Thailand that defined 60 haplotypes clustering in two phylogenetic lineages. In total, 74 nucleotide substitutions were identified and distributed unevenly across the gene. Blockwise analysis of the rates of synonymous ( d S ) and nonsynonymous ( d N ) nucleotide substitutions did not show a significant deviation from neutrality among Thai isolates. However, significantly negative Tajima’s D values were detected in domain I and the loop region of domain II, implying purifying selection. Codon-based analysis of d N / d S has identified 12 and 14 codons under positive and negative selections, respectively. Meanwhile, 85 amino acid substitutions were identified among 80 Thai and 11 non-Thai PiAMA1 sequences. Of these, 48 substituted residues had a significant alteration in physicochemical properties, suggesting positive selection. More than half of these positively selected amino acids (32 of 48) corresponded to the predicted B-cell or T-cell epitopes, suggesting that selective pressure could be mediated by host immunity. Importantly, 14 amino acid substitutions were singletons and predicted to be deleterious that could be subject to ongoing purifying selection or elimination. Besides genetic drift and natural selection, intragenic recombination identified in domain II could generate sequence variation in Piama1 . It is likely that malarial ama1 exhibits interspecies differences in evolutionary histories. Knowledge of the sequence diversity of the Piama1 locus further provides an evolutionary perspective of this important malaria vaccine candidate.

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Genetic diversity of the full length apical membrane antigen-1 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Cited by 7 publications

References 17 publications

Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia

Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia

Genetic diversity and in silico analysis of Plasmodium knowlesi Serine Repeat Antigen (SERA) 3 antigen 2 in Malaysia

Natural selection on apical membrane antigen 1 (AMA1) of an emerging zoonotic malaria parasite Plasmodium inui

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