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Title: Plasmodium vivax HAP2/GCS1 gene exhibits limited genetic diversity among parasite isolates from the Greater Mekong Subregion
Authors: Danni Li
Chunyun Yu
Jian Guo
Yazhou Wang
Yan Zhao
Lin Wang
Myat Thu Soe
Hui Feng
Myat Phone Kyaw
Jetsumon Sattabongkot
Lubin Jiang
Liwang Cui
Xiaotong Zhu
Yaming Cao
Shanghai Oriental Hospital
Institut Pasteur of Shanghai, Chinese Academy of Sciences
Mahidol University
Morsani College of Medicine
China Medical University Shenyang
Myanmar Health Network Organization
Keywords: Immunology and Microbiology;Medicine
Issue Date: 7-Apr-2020
Citation: Parasites and Vectors. Vol.13, No.1 (2020)
Abstract: © 2020 The Author(s). Background: Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium. Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS). Methods: Plasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13-2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation. Results: Sequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (π= 0.00036 ± 0.00003), with the highest πvalue observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright's fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with F ST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations (F ST = 0.60266), and between Thailand and Iran populations (F ST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes. Conclusions: The present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV.[Figure not available: see fulltext.]
ISSN: 17563305
Appears in Collections:Scopus 2020

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