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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 ( F  ST , 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.

Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders