Population Parameters Underlying an Ongoing Soft Sweep in Southeast Asian Malaria Parasites.
Population Parameters Underlying an Ongoing Soft Sweep in Southeast Asian Malaria Parasites.
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DOI：
10.1093/molbev/msw228
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发表时间：
2017-01
影响因子：
10.7
通讯作者：
Nosten F
中科院分区：
文献类型：
--
作者：
Anderson TJ;Nair S;McDew-White M;Cheeseman IH;Nkhoma S;Bilgic F;McGready R;Ashley E;Pyae Phyo A;White NJ;Nosten F
赋予青蒿素抗性 (ART-R) 的多个 kelch13 等位基因目前正在东南亚疟疾寄生虫种群中传播，这提供了独特的机会来观察正在进行的软选择性扫描、研究抗性等位基因为何多次进化并确定疟原虫的基本种群遗传参数。我们对 kelch13 (n = 1,876) 进行了测序，对 75 个侧翼 SNP 进行了基因分型，并测量了泰国西部 (2001-2014) 寄生虫感染的清除率 (n = 3,552)。我们描述了 32 个独立的编码突变，包括与清除率显着降低相关的 kelch13 螺旋桨之外的常见突变。突变首次在 2003 年被观察到，到 2014 年上升到 90%，与 ∼0.079 的选择系数一致。 ART-R 等位基因多样性直到 2012 年才有所上升，然后随着一个等位基因 (C580Y) 传播到高频而下降。适应性等位基因出现的频率由突变率和种群规模决定。有两个因素推动了这种软扫描：(1) 多个 kelch13 氨基酸突变赋予抗性，提供了一个大的突变目标——我们估计目标是 87-163bp。 (2) 群体突变参数(θ = 2Neμ)可以根据ART-R等位基因的频率分布估计为~5.69，表明短期有效群体规模为8.8万至120万。这比根据等位基因频率波动估计的 Ne 高 52-705 倍，这表明我们之前低估了疟原虫的适应性进化能力。我们的中心结论是，回顾性研究可能低估了选择性事件的复杂性，并且与疟疾适应相关的 Ne 比之前估计的要高得多。
Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium. We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001–2014). We describe 32 independent coding mutations including common mutations outside the kelch13 propeller associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ∼0.079. ART-R allele diversity rose until 2012 and then dropped as one allele (C580Y) spread to high frequency. The frequency with which adaptive alleles arise is determined by the rate of mutation and the population size. Two factors drive this soft sweep: (1) multiple kelch13 amino-acid mutations confer resistance providing a large mutational target—we estimate the target is 87–163 bp. (2) The population mutation parameter (Θ = 2Neμ) can be estimated from the frequency distribution of ART-R alleles and is ∼5.69, suggesting that short term effective population size is 88 thousand to 1.2 million. This is 52–705 times greater than Ne estimated from fluctuation in allele frequencies, suggesting that we have previously underestimated the capacity for adaptive evolution in Plasmodium. Our central conclusions are that retrospective studies may underestimate the complexity of selective events and the Ne relevant for adaptation for malaria is considerably higher than previously estimated.
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影响因子：
10.7
作者：
Cheeseman IH;McDew-White M;Phyo AP;Sriprawat K;Nosten F;Anderson TJ
通讯作者：
Anderson TJ
影响因子：
15.8
作者：
Carrara VI;Lwin KM;Phyo AP;Ashley E;Wiladphaingern J;Sriprawat K;Rijken M;Boel M;McGready R;Proux S;Chu C;Singhasivanon P;White N;Nosten F
通讯作者：
Nosten F
柬埔寨恶性疟原虫疟疾中的双氢青蒿素-哌喹抗药性：一项多地点前瞻性队列研究。
DOI：
10.1016/s1473-3099(15)00487-9
发表时间：
2016-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amaratunga C;Lim P;Suon S;Sreng S;Mao S;Sopha C;Sam B;Dek D;Try V;Amato R;Blessborn D;Song L;Tullo GS;Fay MP;Anderson JM;Tarning J;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
56.9
作者：
Joy, DA;Feng, XR;Su, XZ
通讯作者：
Su, XZ
DOI：
10.1073/pnas.78.10.6344
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HARTL, DL;DYKHUIZEN, DE
通讯作者：
DYKHUIZEN, DE