scholarly journals Natural selection and genetic diversity of domain I of Plasmodium falciparum apical membrane antigen-1 on Bioko Island

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ya-Nan Wang ◽  
Min Lin ◽  
Xue-Yan Liang ◽  
Jiang-Tao Chen ◽  
Dong-De Xie ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Amino Acid ◽  
Malaria Vaccine ◽  
Apical Membrane ◽  
Three Dimensional ◽  
B Cell Epitopes ◽  
Apical Membrane Antigen 1 ◽  
Bioko Island ◽  
Domain I

Abstract Background Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. However, antigenic variation and diversity of PfAMA-1 are still major problems to design a universal malaria vaccine based on this antigen, especially against domain I (DI). Detail understanding of the PfAMA-1 gene polymorphism can provide useful information on this potential vaccine component. Here, general characteristics of genetic structure and the effect of natural selection of DIs among Bioko P. falciparum isolates were analysed. Methods 214 blood samples were collected from Bioko Island patients with P. falciparum malaria between 2011 and 2017. A fragment spanning DI of PfAMA-1 was amplified by nested polymerase chain reaction and sequenced. Polymorphic characteristics and the effect of natural selection were analysed using MEGA 5.0, DnaSP 6.0 and Popart programs. Genetic diversity in 576 global PfAMA-1 DIs were also analysed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 program. Results 131 different haplotypes of PfAMA-1 were identified in 214 Bioko Island P. falciparum isolates. Most amino acid changes identified on Bioko Island were found in C1L. 32 amino acid changes identified in PfAMA-1 sequences from Bioko Island were found in predicted RBC-binding sites, B cell epitopes or IUR regions. Overall patterns of amino acid changes of Bioko PfAMA-1 DIs were similar to those in global PfAMA-1 isolates. Differential amino acid substitution frequencies were observed for samples from different geographical regions. Eight new amino acid changes of Bioko island isolates were also identified and their three-dimensional protein structural consequences were predicted. Evidence for natural selection and recombination event were observed in global isolates. Conclusions Patterns of nucleotide diversity and amino acid polymorphisms of Bioko Island isolates were similar to those of global PfAMA-1 DIs. Balancing natural selection across DIs might play a major role in generating genetic diversity in global isolates. Most amino acid changes in DIs occurred in predicted B-cell epitopes. Novel sites mapped on a three dimensional structure of PfAMA-1 showed that these regions were located at the corner. These results may provide significant value in the design of a malaria vaccine based on this antigen.

scholarly journals Genetic Polymorphism and Natural Selection of Apical Membrane Antigen-1 in Plasmodium falciparum Isolates from Vietnam

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1903
Author(s):  
Jung-Mi Kang ◽  
Hương Giang Lê ◽  
Tuấn Cường Võ ◽  
Haung Naw ◽  
Won Gi Yoo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Amino Acid ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Geographical Regions ◽  
Major Amino Acid ◽  
Selection Of

Apical membrane antigen-1 of Plasmodium falciparum (PfAMA-1) is a leading malaria vaccine candidate antigen. However, the genetic diversity of pfama-1 and associated antigenic variation in global P. falciparum field isolates are major hurdles to the design of an efficacious vaccine formulated with this antigen. Here, we analyzed the genetic structure and the natural selection of pfama-1 in the P. falciparum population of Vietnam. A total of 37 distinct haplotypes were found in 131 P. falciparum Vietnamese isolates. Most amino acid changes detected in Vietnamese pfama-1 were localized in the ectodomain, domains I, II, and III. Overall patterns of major amino acid changes in Vietnamese pfama-1 were similar to those of global pfama-1, but the frequencies of the amino acid changes slightly differed by country. Novel amino acid changes were also identified in Vietnamese pfama-1. Vietnamese pfama-1 revealed relatively lower genetic diversity than currently analyzed pfama-1 in other geographical regions, and suggested a distinct genetic differentiation pattern. Evidence for natural selection was detected in Vietnamese pfama-1, but it showed purifying selection unlike the global pfama-1 analyzed so far. Recombination events were also found in Vietnamese pfama-1. Major amino acid changes that were commonly identified in global pfama-1 were mainly localized to predicted B-cell epitopes, RBC-binding sites, and IUR regions. These results provide important information for understanding the genetic nature of the Vietnamese pfama-1 population, and have significant implications for the design of a vaccine based on PfAMA-1.

scholarly journals Population Genetic Analysis of the Plasmodium Falciparum Erythrocyte Binding Antigen-175 (EBA-175) Gene in Equatorial Guinea

2021 ◽  
Author(s):  
Pei-Kui Yang ◽  
Xue-Yan Liang ◽  
Min Lin ◽  
Jiang-Tao Chen ◽  
Hui-Ying Huang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Malaria Vaccine ◽  
Blood Stage ◽  
Equatorial Guinea ◽  
Bioko Island ◽  
Erythrocyte Binding ◽  
Region Ii ◽  
Blood Stage Malaria

Abstract Background: Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms in the PfEBA-175 gene among global P. falciparum populations have prevented the development of effective vaccines based on this gene. At the same time, the dimorphism of the F- and C-fragments associated with high endemic of severe malaria has been described. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175.Methods: A total of 218 blood samples were collected from patients with P. falciparum malaria on Bioko Island and Bata district in 2018 and 2019. The allelic dimorphism of PfEBA-175 region II was investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Genetic diversity in 312 global PfEBA-175 region II sequences was also analyzed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program.Results: Allelic dimorphism of PfEBA-175 was identified in the study area, and the frequency of the F-fragment was higher than that of the C-fragment in both Bioko Island and Bata district populations. Additionally, single infections (87.80%) were more frequent than mixed infections (12.20%). A total of 49 monoclonal PfEBA-175 region II sequences of Bioko Island and Bata district were sequenced successfully. PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and -0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (Fst>0.15, P<0.05). A total of 312 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging by PolyPhen-2. Among them, mutations A34T, K301N and L305V led to significant increases in the free energy difference (ΔΔG>1), indicating destabilization of the protein structure.Conclusions: This study proved the dimorphism of PfEBA-175, and also demonstrated that the F-fragment was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar to those of isolates worldwide. High levels of recombination events were observed in PfEBA-175 isolates globally, suggesting that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

scholarly journals Genetic diversity and effect of natural selection at apical membrane antigen-1 (AMA-1) among Iranian Plasmodium vivax isolates

2014 ◽  
Vol 61 (5) ◽  
pp. 385-393 ◽  
Author(s):  
Ahmad Reza Esmaeili Rastaghi ◽  
Fatemeh Nedaei ◽  
Hossein Nahrevanian ◽  
Nazanin Hoseinkhan
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Plasmodium Vivax ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

scholarly journals Genetic Diversity and Selection of Plasmodium vivax Apical Membrane Antigen-1 in China–Myanmar Border of Yunnan Province, China, 2009–2016

2022 ◽  
Vol 11 ◽  
Author(s):  
Yan-Bing Cui ◽  
Hai-Mo Shen ◽  
Shen-Bo Chen ◽  
Kokouvi Kassegne ◽  
Tian-Qi Shi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Yunnan Province ◽  
Malaria Vaccine ◽  
Apical Membrane ◽  
High Genetic Diversity ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Public Data ◽  
Selection Of

Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is an important vaccine candidate for vivax malaria. However, antigenic variation within PvAMA-1 is a major obstacle to the design of a global protective malaria vaccine. In this study, we analyzed the genetic polymorphism and selection of the PvAMA-1 gene from 152 P. vivax isolates from imported cases to China, collected in the China–Myanmar border (CMB) area in Yunnan Province (YP) during 2009–2011 (n = 71) and 2014–2016 (n = 81), in comparison with PvAMA-1 gene information from Myanmar (n = 73), collected from public data. The overall nucleotide diversity of the PvAMA-1 gene from the 152 YP isolates was 0.007 with 76 haplotypes identified (Hd = 0.958). Results from the population structure suggested three groups among the YP and Myanmar isolates with optimized clusters value of K = 7. In addition, YP (2014–2016) isolates generally lacked some K components that were commonly found in YP (2009–2011) and Myanmar. Meanwhile, PvAMA-1 domain I is found to be the dominant target of positive diversifying selection and most mutation loci were found in this domain. The mutation frequencies of D107N/A, R112K/T, K120R, E145A, E277K, and R438H in PvAMA-1 were more than 70% in the YP isolates. In conclusion, high genetic diversity and positive selection were found in the PvAMA-1 gene from YP isolates, which are significant findings for the design and development of PvAMA-1-based malaria vaccine.

scholarly journals Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (EBA-175) gene in Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Pei-Kui Yang ◽  
Xue-Yan Liang ◽  
Min Lin ◽  
Jiang-Tao Chen ◽  
Hui-Ying Huang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Malaria Vaccine ◽  
Blood Stage ◽  
Equatorial Guinea ◽  
Fixation Index ◽  
Bioko Island ◽  
Erythrocyte Binding ◽  
Blood Stage Malaria

Abstract Background Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. Methods The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. Results Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and − 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. Conclusions This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

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