Genetic Diversity in New Members of the Reticulocyte Binding Protein Family in Thai Plasmodium vivax Isolates

Abstract Background Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. Methods pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. Results The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. Conclusions The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.

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Genetic diversity and natural selection of Duffy binding protein of Plasmodium vivax Korean isolates

Acta Tropica ◽

10.1016/j.actatropica.2012.09.016 ◽

2013 ◽

Vol 125 (1) ◽

pp. 67-74 ◽

Cited By ~ 24

Author(s):

Hye-Lim Ju ◽

Jung-Mi Kang ◽

Sung-Ung Moon ◽

Young-Yil Bahk ◽

Pyo-Yun Cho ◽

...

Keyword(s):

Genetic Diversity ◽

Natural Selection ◽

Plasmodium Vivax ◽

Binding Protein ◽

Duffy Binding Protein ◽

Selection Of

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Genetic diversity of Plasmodium vivax Duffy Binding Protein II (PvDBPII) under unstable transmission and low intensity malaria in Sri Lanka

Infection Genetics and Evolution ◽

10.1016/j.meegid.2011.04.023 ◽

2011 ◽

Vol 11 (6) ◽

pp. 1327-1339 ◽

Cited By ~ 25

Author(s):

Prasad H. Premaratne ◽

B. Ramesh Aravinda ◽

Ananias A. Escalante ◽

Preethi V. Udagama

Keyword(s):

Genetic Diversity ◽

Sri Lanka ◽

Plasmodium Vivax ◽

Binding Protein ◽

Duffy Binding Protein ◽

Low Intensity ◽

Unstable Transmission

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Genetic Diversity of Plasmodium vivax Reticulocyte Binding Protein 2b in Global Parasite Populations

10.21203/rs.3.rs-1023914/v1 ◽

2021 ◽

Author(s):

xuexing zhang ◽

Haichao Wei ◽

Yangminghui Zhang ◽

Yan Zhao ◽

Lin Wang ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Vaccine Development ◽

Balancing Selection ◽

Binding Protein ◽

Critical Role ◽

Binding Region ◽

Geographical Separation ◽

Antibody Titers ◽

Parasite Populations

Abstract BackgroundPlasmodium vivax reticulocyte binding protein 2b (PvRBP2b) plays a critical role in parasite invasion of reticulocytes by binding the transferring receptor 1. PvRBP2b is a vaccine candidate since the antibody titers against PvRBP2b recombinant proteins are negatively correlated with the parasitemia and risk of vivax malaria. This study aims to analyze the genetic diversity of the PvRBP2b gene in the global P. vivax populations. MethodsThe near full-length PvRBP2b nucleotide sequences (190-8349 bp) were obtained from 88 P. vivax isolates collected from the China–Myanmar border (n=44) and Thailand (n=44). Additional 224 sequences of PvRBP2b were retrieved from genome sequences from the global parasite populations. The genetic diversity, neutral selections, haplotypes distribution and genetic differentiation of PvRBP2b were examined. ResultsThe genetic diversity of PvRBP2b was distributed unevenly with the peak in the reticulocyte binding region in the N-terminus and subjected to the balancing selection. Several amino acid variants were found in all or nearly all endemic fields. However, the critical residues responsible for reticulocyte binding were highly conserved. There was substantial population differentiation according to the geographical separation. The distribution of haplotypes in the reticulocyte binding region varied among regions; even the two major haplotypes Hap_6 and Hap_8 were found in only five populations. ConclusionsOur data showed considerable genetic variations of PvRBPb in global parasite populations, and the geographic divergence may pose a challenge to PvRBP2b-based vaccine development.

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Genetic diversity in two Plasmodium vivax protein ligands for reticulocyte invasion

10.1101/328757 ◽

2018 ◽

Author(s):

Camille Roesch ◽

Jean Popovici ◽

Sophalai Bin ◽

Vorleak Run ◽

Saorin Kim ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Binding Protein ◽

Invasion Pathways ◽

Genomic Changes ◽

Synonymous Mutations ◽

Protein Ligands ◽

Immune Pressure ◽

Erythrocyte Binding ◽

Duffy Negative

AbstractThe interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the genetic diversity of the two main protein ligands for reticulocyte invasion, PvDBP and P. vivax Erythrocyte Binding Protein (PvEBP), we analyzed 458 isolates collected in Cambodia and Madagascar. First, we observed a high proportion of isolates with multiple copies PvEBP from Madagascar (56%) where Duffy negative and positive individuals coexist compared to Cambodia (19%) where Duffy-negative population is virtually absent. Whether the gene amplification observed is responsible for alternate invasion pathways remains to be tested. Second, we found that the PvEBP gene was less diverse than PvDBP gene (12 vs. 33 alleles) but provided evidence for an excess of nonsynonymous mutations with the complete absence of synonymous mutations. This finding reveals that PvEBP is under strong diversifying selection, and confirms the importance of this protein ligand in the invasion process of the human reticulocytes and as a target of acquired immunity. These observations highlight how genomic changes in parasite ligands improve the fitness of P. vivax isolates in the face of immune pressure and receptor polymorphisms.

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