Limited genetic diversity in the PvK12 Kelch protein in Plasmodium vivax isolates from Southeast Asia.
BACKGROUND
Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Mutations in the Kelch propeller domain of PfK13 are the only known molecular markers for artemisinin resistance in this parasite. Over 100 non-synonymous mutations have been identified in PfK13 from various malaria endemic regions. This study aimed to investigate the genetic diversity of PvK12, the Plasmodium vivax ortholog of PfK13, in parasite populations from Southeast Asia, where artemisinin resistance in P. falciparum has emerged.


METHODS
The PvK12 sequences in 120 P. vivax isolates collected from Thailand (22), Myanmar (32) and China (66) between 2004 and 2008 were obtained and 353 PvK12 sequences from worldwide populations were retrieved for further analysis.


RESULTS
These PvK12 sequences revealed a very low level of genetic diversity (π = 0.00003) with only three single nucleotide polymorphisms (SNPs). Of these three SNPs, only G581R is nonsynonymous. The synonymous mutation S88S is present in 3% (1/32) of the Myanmar samples, while G704G and G581R are present in 1.5% (1/66) and 3% (2/66) of the samples from China, respectively. None of the mutations observed in the P. vivax samples were associated with artemisinin resistance in P. falciparum. Furthermore, analysis of 473 PvK12 sequences from twelve worldwide P. vivax populations confirmed the very limited polymorphism in this gene and detected only five distinct haplotypes.


CONCLUSIONS
The PvK12 sequences from global P. vivax populations displayed very limited genetic diversity indicating low levels of baseline polymorphisms of PvK12 in these areas.
Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, 110013, China. Wangmeilian_m@hotmail.com.|Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA, 16802, USA. Wangmeilian_m@hotmail.com.
Meilian
M
Wang
Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA, 16802, USA.
Faiza Amber
FA
Siddiqui
Dalian Institute of Biotechnology, Dalian, Liaoning Province, China.
Qi
Q
Fan
Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, 110013, China.
Enjie
E
Luo
Department of Immunology, College of Basic Medical Sciences, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, 110013, China.
Yaming
Y
Cao
Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, 110013, China. luc2@psu.edu.|Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA, 16802, USA. luc2@psu.edu.
Liwang
L
Cui
D002681:China; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D016780:Malaria, Vivax / Q000469:parasitology*; D009154:Mutation; D002052:Myanmar; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013785:Thailand
D016054:DNA, Protozoan; D015800:Protozoan Proteins
Artemisinin resistance; Genetic diversity; Kelch domain protein; Malaria; PfK13; Plasmodium vivax; PvK12