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Title: Genetic Diversity and Lack of Artemisinin Selection Signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion
Authors: Miao Miao
Zenglei Wang
Zhaoqing Yang
Lili Yuan
Daniel M. Parker
Chaturong Putaporntip
Somchai Jongwutiwes
Phonepadith Xangsayarath
Tiengkham Pongvongsa
Hazuhiko Moji
Trinh Dinh Tuong
Tomoko Abe
Shusuke Nakazawa
Myat Phone Kyaw
Guiyun Yan
Jeeraphat Sirichaisinthop
Jetsumon Sattabongkot
Jianbing Mu
Xin zhuan Su
Osamu Kaneko
Liwang Cui
Pennsylvania State University
Kunming Medical College
Chulalongkorn University
Nagasaki University
Station of Malariology
National Institutes for the Humanities, Research Institute for Humanity and Nature
National Institute of Malariology, Parasitology and Entomology Hanoi
Parasitology Research Division
University of California, Irvine
Vector Borne Disease Training Center
Mahidol University
National Institute of Allergy and Infectious Diseases
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 26-Mar-2013
Citation: PLoS ONE. Vol.8, No.3 (2013)
Abstract: The recent detection of clinical Artemisinin (ART) resistance manifested as delayed parasite clearance in the Cambodia-Thailand border area raises a serious concern. The mechanism of ART resistance is not clear; but the P. falciparum sarco/endoplasmic reticulum Ca2+-ATPase (PfSERCA or PfATP6) has been speculated to be the target of ARTs and thus a potential marker for ART resistance. Here we amplified and sequenced pfatp6 gene (~3.6 Kb) in 213 samples collected after 2005 from the Greater Mekong Subregion, where ART drugs have been used extensively in the past. A total of 24 single nucleotide polymorphisms (SNPs), including 8 newly found in this study and 13 nonsynonymous, were identified. However, these mutations were either uncommon or also present in other geographical regions with limited ART use. None of the mutations were suggestive of directional selection by ARTs. We further analyzed pfatp6 from a worldwide collection of 862 P. falciparum isolates in 19 populations from Asia, Africa, South America and Oceania, which include samples from regions prior to and after deployments ART drugs. A total of 71 SNPs were identified, resulting in 106 nucleotide haplotypes. Similarly, many of the mutations were continent-specific and present at frequencies below 5%. The most predominant and perhaps the ancestral haplotype occurred in 441 samples and was present in 16 populations from Asia, Africa, and Oceania. The 3D7 haplotype found in 54 samples was the second most common haplotype and present in nine populations from all four continents. Assessment of the selection strength on pfatp6 in the 19 parasite populations found that pfatp6 in most of these populations was under purifying selection with an average dN/dSratio of 0.333. Molecular evolution analyses did not detect significant departures from neutrality in pfatp6 for most populations, challenging the suitability of this gene as a marker for monitoring ART resistance.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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