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

Abstract

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.

Genetic diversity and molecular evolution of Plasmodium vivax Duffy Binding Protein and Merozoite Surface Protein-1 in northwestern Thailand

“…The haplotype diversity of pvdbp II from the northwestern Thailand population (Hd = 0.849 ± 0.024) was comparable to that reported from eastern Myanmar (0.850 ± 0.021) using specimens collected in 2016 ( Hu et al, 2019 ). Most (12/14) SNPs detected on pvdbp II in this study have been reported previously ( Almeida-de-Oliveira et al, 2020a ; Hoque et al, 2018 ; Hu et al, 2019 ; Shi et al, 2021 ). In contrast, many novel mutations were found in pvmsp1 42kDa , consistent with its higher global diversity and greater capacity to accommodate mutations.…”

“…Amino acid changes were found at various positions in both parasite proteins. Of 131-aa in the pvdbp II fragment, 14 were mutated, 12 of which (K326E, N330D, G339D, E340K, K341N, H345R, S353T, T359R, N372K, I374M, I379L, W392R; numbers referenced to the P01 strain) had been previously reported from Brazil ( Almeida-de-Oliveira et al, 2020a ), Myanmar ( Hu et al, 2019 ), Sudan ( Hoque et al, 2018 ), and China ( Shi et al, 2021 ) ( Fig. 4D ).…”

“…Haplotype D7 was predominant with 20 genetically identical isolates, while haplotypes with P01 reference (D1) were at a frequency of 0.029, including 2 isolates ( Supplementary File 2: Table S3 ). Ten of fifteen pvdbp II haplotypes were shared globally, including Latin and South America, Central Asia, and Oceania ( Almeida-de-Oliveira et al, 2020a ; Cole-Tobian et al, 2002 ; Gonzalez-Ceron et al, 2015 ; Goryacheva et al, 2018 ; Shi et al, 2021 ). The distribution of these haplotypes in 5 P. vivax endemic regions revealed that these areas shared at least one northwestern Thailand haplotype.…”

“…To assess population differentiation between northwestern Thailand and other geographical origins, fixation index (F st ) was calculated with the global sequences retrieved from 8 countries, including Brazil (BRA), China (CHA), Kyrgyz Republic (KYR), Mexico (MEX), Papua New Guinea (PNG), Cambodia (CAM), Indonesia (IDN), and Nicaragua (NIC) ( Table 3 ) ( Almeida-de-Oliveira et al, 2020b , 2020a ; Cole-Tobian et al, 2002 ; Flores-Alanis et al, 2022 ; Gonzalez-Ceron et al, 2015 ; Goryacheva et al, 2018 ; Gutierrez et al, 2016 ; Murhandarwati et al, 2020 ; Parobek et al, 2014 ; Shi et al, 2021 ). The value of F st ranges from 0 to 1.…”

“…Homologous DNA sequences from different parasite populations were retrieved from the NCBI Genbank to compare genetic diversity between northwestern Thailand and global isolates. pvdbp II : For Brazil ( n = 137, MN223747–MN223883) ( Almeida-de-Oliveira et al, 2020a ), China ( n = 124, MZ765947–MZ766070) ( Shi et al, 2021 ), Papua New Guinea ( n = 88, AF469515–AF469602) ( Cole-Tobian et al, 2002 ), Mexico ( n = 35, KP759780–KP759814) ( Gonzalez-Ceron et al, 2015 ), and Kyrgyz Republic ( n = 21, MK014215–MK014235) ( Goryacheva et al, 2018 ). pvmsp1 42kDa : For Brazil ( n = 122, MT074744–MT074865) ( Almeida-de-Oliveira et al, 2020b ), Mexico ( n = 163, OL411675–OL411837) ( Flores-Alanis et al, 2022 ), Indonesia ( n = 52, MK733842–MK733893) ( Murhandarwati et al, 2020 ), Nicaragua ( n = 92, KR871926–KR872017) ( Gutierrez et al, 2016 ), and Cambodia ( n = 44, JX461286–JX461295, JX461297–JX461298, JX461300–JX461310, JX461312–JX461317, and JX461319–JX461333) ( Parobek et al, 2014 ).…”