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

Abstract

AbstractBackgroundMerozoite 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 withPlasmodium vivaxbecoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity ofP. vivax Duffy-binding proteingene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from globalP. vivaxpopulations.Methodspvdbp-II sequences were obtained from 85 and 82 clinicalP. vivaxisolates from the eastern and western Myanmar borders, respectively. In addition, 504pvdbp-II sequences from nineP. vivaxpopulations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population.ResultsThe nucleotide diversity of thepvdbp-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 inpvdbp-II gene inP. vivaxisolates from the eastern Myanmar area.P. vivaxparasite 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 thepvdbp-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) inP. vivaxpopulations from the eastern and western borders of Myanmar.ConclusionsThepvdbp-II gene is genetically diverse in the eastern and western Myanmar borderP. vivaxpopulations. Positive natural selection and recombination occurred inpvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of theP. vivaxpopulations in the GMS. These results can help understand the evolution of theP. vivaxpopulations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.