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

Autor: Somchai Jongwutiwes, Jeeraphat Sirichaisinthop, Shusuke Nakazawa, Chaturong Putaporntip, Tiengkham Pongvongsa, Hazuhiko Moji, Guiyun Yan, Jetsumon Sattabongkot, Myat Phone Kyaw, Zhaoqing Yang, Tomoko Abe, Daniel M. Parker, Osamu Kaneko, Xin-zhuan Su, Liwang Cui, Miao Miao, Trinh Dinh Tuong, Zenglei Wang, Phonepadith Xangsayarath, Jianbing Mu, Lili Yuan
Rok vydání: 2012
Předmět:
Nonsynonymous substitution
Drug Resistance
lcsh:Medicine
Population genetics
Protozoology
Genetic analysis
0302 clinical medicine
Genotype
Malaria
Falciparum
lcsh:Science
Asia
Southeastern
Genetics
0303 health sciences
Multidisciplinary
Artemisinins
3. Good health
Phylogeography
Infectious Diseases
Medicine
Research Article
030231 tropical medicine
Plasmodium falciparum
Single-nucleotide polymorphism
Calcium-Transporting ATPases
Biology
Polymorphism
Single Nucleotide
Microbiology
03 medical and health sciences
Antimalarials
Molecular evolution
Parasitic Diseases
Humans
Selection
Genetic
030304 developmental biology
Genetic diversity
Evolutionary Biology
Population Biology
lcsh:R
Haplotype
Computational Biology
Tropical Diseases (Non-Neglected)
DNA
Protozoan
Malaria
Haplotypes
Mutation
Genetic Polymorphism
Parastic Protozoans
lcsh:Q
Population Genetics
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 3, p e59192 (2013)
ISSN: 1932-6203
Popis: 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/dS 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.
PLoS ONE, 8(3), e59192; 2013
Databáze: OpenAIRE
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