Limits...
Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene.

Faber BW, Abdul Kadir K, Rodriguez-Garcia R, Remarque EJ, Saul FA, Vulliez-Le Normand B, Bentley GA, Kocken CH, Singh B - PLoS ONE (2015)

Bottom Line: Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions.These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans.The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

ABSTRACT
Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.

No MeSH data available.


Related in: MedlinePlus

Polymorphic residues in the PkAMA1 protein.High frequency polymorphic sites in red, bold and highlighted in white; low frequency polymorphic sites in black.
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pone.0124400.g001: Polymorphic residues in the PkAMA1 protein.High frequency polymorphic sites in red, bold and highlighted in white; low frequency polymorphic sites in black.

Mentions: The translated DNA sequences were aligned (Fig 1) and 27 haplotypes were identified from the protein sequences (S1 Table). One haplotype occurred nine times, the next most frequent haplotype occurred six times, then two occurring five times, one occurring four times, one occurring three times, four occurring twice and finally 17 occurred only once (S1 Table). Interestingly, 11 haplotypes were found exclusively in Kapit Division, another 11 exclusively in Betong Division.


Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene.

Faber BW, Abdul Kadir K, Rodriguez-Garcia R, Remarque EJ, Saul FA, Vulliez-Le Normand B, Bentley GA, Kocken CH, Singh B - PLoS ONE (2015)

Polymorphic residues in the PkAMA1 protein.High frequency polymorphic sites in red, bold and highlighted in white; low frequency polymorphic sites in black.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400157&req=5

pone.0124400.g001: Polymorphic residues in the PkAMA1 protein.High frequency polymorphic sites in red, bold and highlighted in white; low frequency polymorphic sites in black.
Mentions: The translated DNA sequences were aligned (Fig 1) and 27 haplotypes were identified from the protein sequences (S1 Table). One haplotype occurred nine times, the next most frequent haplotype occurred six times, then two occurring five times, one occurring four times, one occurring three times, four occurring twice and finally 17 occurred only once (S1 Table). Interestingly, 11 haplotypes were found exclusively in Kapit Division, another 11 exclusively in Betong Division.

Bottom Line: Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions.These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans.The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

ABSTRACT
Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.

No MeSH data available.


Related in: MedlinePlus