Population genetic structure and natural selection of  Plasmodium falciparum  apical membrane antigen-1 in Myanmar isolates

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Abstract

Background

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is one of leading blood stage malaria vaccine candidates. However, genetic variation and antigenic diversity identified in global PfAMA-1 are major hurdles in the development of an effective vaccine based on this antigen. In this study, genetic structure and the effect of natural selection of PfAMA-1 among Myanmar P. falciparum isolates were analysed.

Methods

Blood samples were collected from 58 Myanmar patients with falciparum malaria. Full-length PfAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. PfAMA-1 sequence of each isolate was sequenced. Polymorphic characteristics and effect of natural selection were analysed with using DNASTAR, MEGA4, and DnaSP programs. Polymorphic nature and natural selection in 459 global PfAMA-1 were also analysed.

Results

Thirty-seven different haplotypes of PfAMA-1 were identified in 58 Myanmar P. falciparum isolates. Most amino acid changes identified in Myanmar PfAMA-1 were found in domains I and III. Overall patterns of amino acid changes in Myanmar PfAMA-1 were similar to those in global PfAMA-1. However, frequencies of amino acid changes differed by country. Novel amino acid changes in Myanmar PfAMA-1 were also identified. Evidences for natural selection and recombination event were observed in global PfAMA-1. Among 51 commonly identified amino acid changes in global PfAMA-1 sequences, 43 were found in predicted RBC-binding sites, B-cell epitopes, or IUR regions.

Conclusions

Myanmar PfAMA-1 showed similar patterns of nucleotide diversity and amino acid polymorphisms compared to those of global PfAMA-1. Balancing natural selection and intragenic recombination across PfAMA-1 are likely to play major roles in generating genetic diversity in global PfAMA-1. Most common amino acid changes in global PfAMA-1 were located in predicted B-cell epitopes where high levels of nucleotide diversity and balancing natural selection were found. These results highlight the strong selective pressure of host immunity on the PfAMA-1 gene. These results have significant implications in understanding the nature of Myanmar PfAMA-1 along with global PfAMA-1. They also provide useful information for the development of effective malaria vaccine based on this antigen.

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Most cited references 50

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A proteomic view of the Plasmodium falciparum life cycle.

Laurence Florens, Michael Washburn, J. Raine … (2002)

The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression.

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The estimation of population differentiation with microsatellite markers.

François Balloux, Nicolas Lugon-Moulin (2002)

Microsatellite markers are routinely used to investigate the genetic structuring of natural populations. The knowledge of how genetic variation is partitioned among populations may have important implications not only in evolutionary biology and ecology, but also in conservation biology. Hence, reliable estimates of population differentiation are crucial to understand the connectivity among populations and represent important tools to develop conservation strategies. The estimation of differentiation is c from Wright's FST and/or Slatkin's RST, an FST -analogue assuming a stepwise mutation model. Both these statistics have their drawbacks. Furthermore, there is no clear consensus over their relative accuracy. In this review, we first discuss the consequences of different temporal and spatial sampling strategies on differentiation estimation. Then, we move to statistical problems directly associated with the estimation of population structuring itself, with particular emphasis on the effects of high mutation rates and mutation patterns of microsatellite loci. Finally, we discuss the biological interpretation of population structuring estimates.

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A field trial to assess a blood-stage malaria vaccine.

Mahamadou Thera, Ogobara K. Doumbo, Drissa Coulibaly … (2011)

Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.).

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Author and article information

Contributors

Byoung-Kuk Na: bkna@gnu.ac.kr

Journal

Journal ID (nlm-ta): Malar J

Journal ID (iso-abbrev): Malar. J

Title: Malaria Journal

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2875

Publication date (Electronic): 7 February 2018

Publication date PMC-release: 7 February 2018

Publication date Collection: 2018

Volume: 17

Electronic Location Identifier: 71

Affiliations

[1 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, , Gyeongsang National University College of Medicine, ; Jinju, 52727 Republic of Korea

[2 ]ISNI 0000 0001 0661 1492, GRID grid.256681.e, BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, , Gyeongsang National University, ; Jinju, 52727 Republic of Korea

[3 ]Department of Medical Research Pyin Oo Lwin Branch, Pyin Oo Lwin, Myanmar

[4 ]ISNI 0000 0001 2364 8385, GRID grid.202119.9, Department of Tropical Medicine and Inha Research Institute for Medical Sciences, , Inha University College of Medicine, ; Incheon, 22212 Republic of Korea

[5 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Microbiology, , Ajou University College of Medicine, ; Suwon, 16499 Republic of Korea

[6 ]ISNI 0000 0004 0533 4755, GRID grid.410899.d, Present Address: Department of Infection Biology, Zoonosis Research Center, School of Medicine, , Wonkwang University, ; Iksan, 54538 Republic of Korea

[7 ]Present Address: Planning and Management Division, Nakdonggang National Institute of Biological Resources, Sangju, 37242 Republic of Korea

Article

Publisher ID: 2215

DOI: 10.1186/s12936-018-2215-7

PMC ID: 5804060

PubMed ID: 29415731

SO-VID: ec1c8f10-90c8-49f6-9579-09e24a2287c3

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 1 October 2017

Date accepted : 30 January 2018

Funding

Funded by: Natioanl Research Foundation of Korea

Award ID: NRF-2015R1A2A2A01004310

Award Recipient : Byoung-Kuk Na

Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;

Award ID: NRF-2015K1A3A9A01034893

Award Recipient : Tong-Soo Kim

Custom metadata

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: plasmodium falciparum,apical membrane antigen-1,genetic diversity,natural selection,myanmar

Data availability:

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: plasmodium falciparum, apical membrane antigen-1, genetic diversity, natural selection, myanmar

Population genetic structure and natural selection of Plasmodium falciparum apical membrane antigen-1 in Myanmar isolates

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Abstract

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Most cited references 50

A proteomic view of the Plasmodium falciparum life cycle.

The estimation of population differentiation with microsatellite markers.

A field trial to assess a blood-stage malaria vaccine.

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