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Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion

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tm-ar-jetsumon-2013.pdf (578.14 KB)

Accepted Date

2013-02-12

Issued Date

2013

Copyright Date

2013

Resource Type

Article

Language

eng

ISSN

1932-6203 (electronic)

DOI

10.1371/journal.pone.0059192

Rights

Mahidol University

Rights Holder(s)

PLoS ONE

Bibliographic Citation

Miao M, Wang Z, Yang Z, Yuan L, Parker DM, Putaporntip C, et al. Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion. PLoS One. 2013;8(3):e59192.

Suggested Citation

Miao, Miao, Wang, Zenglei, Yang, Zhaoqing, Yuan, Lili, Parker, Daniel M., Chaturong Putaporntip, Somchai Jongwutiwes, Xangsayarath, Phonepadith, Pongvongsa, Tiengkham, Moji, Hazuhiko, Tuong, Trinh Dinh, Abe, Tomoko, Nakazawa, Shusuke, Kyaw, Myat Phone, Yan, Guiyun, Jeeraphat Sirichaisinthop, Jetsumon Sattabongkot, เจตสุมน สัตตบงกช, Mu, Jianbing, Su, Xin-zhuan, Kaneko, Osamu, Cui, Liwang Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion. Miao M, Wang Z, Yang Z, Yuan L, Parker DM, Putaporntip C, et al. Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion. PLoS One. 2013;8(3):e59192.. doi:10.1371/journal.pone.0059192 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/752

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Title

Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion

Author(s)

Miao, Miao
 Wang, Zenglei
 Yang, Zhaoqing
 Yuan, Lili
 Parker, Daniel M.
 Chaturong Putaporntip
 Somchai Jongwutiwes
 Xangsayarath, Phonepadith
 Pongvongsa, Tiengkham
 Moji, Hazuhiko
 Tuong, Trinh Dinh
 Abe, Tomoko
 Nakazawa, Shusuke
 Kyaw, Myat Phone
 Yan, Guiyun
 Jeeraphat Sirichaisinthop
 Jetsumon Sattabongkot
 เจตสุมน สัตตบงกช
 Mu, Jianbing
 Su, Xin-zhuan
 Kaneko, Osamu
 Cui, Liwang

Corresponding Author(s)

Cui, Liwang

Other Contributor(s)

Mahidol University. Faculty of Tropical Medicine.

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 Ca(2+)-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 d(N)/d(S) ratio 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.

Keyword(s)

Genetic
 Plasmodium falciparum
 Open Access article

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URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/752

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TM-Article