scholarly journals Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Li-Yun Lin ◽  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Dong-De Xie ◽  
Jiang-Tao Chen ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Protein Structure ◽  
Transmembrane Protein ◽  
Fixation Index ◽  
Bioko Island ◽  
Adhesive Protein ◽  
Trap Gene ◽  
Selection Of

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

scholarly journals Genetic Diversity and Natural Selection on the Thrombospondin-Related Adhesive Protein (TRAP) Gene of Plasmodium Falciparum on Bioko Island, Equatorial Guinea and Global Comparative Analysis

2020 ◽  
Author(s):  
Li-Yun Lin ◽  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Dong-De Xie ◽  
Jiang-Tao Chen ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Protein Structure ◽  
Transmembrane Protein ◽  
Fixation Index ◽  
Effective Vaccine ◽  
Bioko Island ◽  
Adhesive Protein ◽  
Trap Gene ◽  
Selection Of

Abstract Background: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As the potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was painted. Methods: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools.Results: A total of 119 monoclonal Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p<0.05) and the nagetive Tajima's D (-0.41438) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst>0.15, p<0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG>1) indicated a destabilization of protein structure. Conclusions: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes) and the global PfTRAP gene is under natural selection, which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations showed destructive to the protein structure or function and deserve further study and continuous monitoring.

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.

scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein (PfCSP) and mismatches against RTS, S/AS01 malaria vaccine observed on Bioko Island, Equatorial Guinea and globally

2020 ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Genetic Polymorphisms ◽  
Vaccine Efficacy ◽  
Malaria Vaccine ◽  
Repetitive Sequences ◽  
Circumsporozoite Protein ◽  
Bioko Island ◽  
Selection Of

Abstract Backgroud RTS, S/AS01 is a Plasmodium falciparum circumsporozoite protein ( PfCSP ) based anti-malaria vaccine, but various genetic polymorphisms of PfCSP among global P. falciparum population could lead to mismatch against the PfCSP - based vaccine and reduce vaccine efficacy. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko as well as global P. falciparum population. Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analyzed with 2200 global PfCSP sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of PfCSP showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko PfCSP gene had no obvious deviation from African mainland PfCSP (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global PfCSP displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global PfCSP C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 vaccine strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal. The overall vaccine efficacy might be influenced by the low proportion of vaccine-matched isolates in global parasites population. Genetic polymorphism and geographical characteristics should be considered for future improvement of RTS, S/AS01.

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 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 Genetic diversity and population structure of ridge gourd (Luffa acutangula) accessions in a Thailand collection using SNP markers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Grimar Abdiel Perez ◽  
Pumipat Tongyoo ◽  
Julapark Chunwongse ◽  
Hans de Jong ◽  
Anucha Wongpraneekul ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Germplasm Collection ◽  
Snp Markers ◽  
Fixation Index ◽  
Breeding Programs ◽  
Total Fixation ◽  
Unrooted Phylogenetic Tree ◽  
Luffa Acutangula ◽  
Selection Of

AbstractThis study explored a germplasm collection consisting of 112 Luffa acutangula (ridge gourd) accessions, mainly from Thailand. A total of 2834 SNPs were used to establish population structure and underlying genetic diversity while exploring the fruit characteristics together with genetic information which would help in the selection of parental lines for a breeding program. The study found that the average polymorphism information content value of 0.288 which indicates a moderate genetic diversity for this L. acutangula germplasm. STRUCTURE analysis (ΔK at K = 6) allowed us to group the accessions into six subpopulations that corresponded well with the unrooted phylogenetic tree and principal coordinate analyses. When plotted, the STRUCTURE bars to the area of collection, we observed an admixed genotype from surrounding accessions and a geneflow confirmed by the value of FST = 0.137. AMOVA based on STRUCTURE clustering showed a low 12.83% variation between subpopulations that correspond well with the negative inbreeding coefficient value (FIS =  − 0.092) and low total fixation index (FIT = 0.057). There were distinguishing fruit shapes and length characteristics in specific accessions for each subpopulation. The genetic diversity and different fruit shapes in the L. acutangula germplasm could benefit the ridge gourd breeding programs to meet the demands and needs of consumers, farmers, and vegetable exporters such as increasing the yield of fruit by the fruit width but not by the fruit length to solve the problem of fruit breakage during exportation.

scholarly journals Diversifying Selection on the Thrombospondin-Related Adhesive Protein (TRAP) Gene of Plasmodium falciparum in Thailand

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e90522 ◽  
Author(s):  
Jun Ohashi ◽  
Yuji Suzuki ◽  
Izumi Naka ◽  
Hathairad Hananantachai ◽  
Jintana Patarapotikul
Keyword(s):  
Plasmodium Falciparum ◽  
Diversifying Selection ◽  
Adhesive Protein ◽  
Trap Gene

scholarly journals Genetic Diversity and Natural Selection of Plasmodium vivax Duffy Binding Protein-II From China-Myanmar Border of Yunnan Province, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian-Qi Shi ◽  
Hai-Mo Shen ◽  
Shen-Bo Chen ◽  
Kokouvi Kassegne ◽  
Yan-Bing Cui ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Positive Selection ◽  
Plasmodium Vivax ◽  
Yunnan Province ◽  
Duffy Binding Protein ◽  
Synonymous Mutations ◽  
Selection Of

Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009–2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.

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