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Reference: Anderson, TJC, Nair, S, McDew-White, M et al., (2016). Population parameters underlying an ongoing soft sweep in Southeast Asian malaria parasites. Molecular Biology and Evolution, 34 (1), 131-144.Citable link to this page:

 

Population parameters underlying an ongoing soft sweep in Southeast Asian malaria parasites.

Abstract: Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asia 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 can confer resistance providing a large mutational target – we estimate the target is 87 - 163bp. (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.

Publication status:PublishedPeer Review status:Peer reviewed Funder: Bill and Melinda Gates Foundation   Funder: National Institutes for Health   Notes:© The Authors 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions[at]oup.com

Bibliographic Details

Publisher: Oxford University Press

Publisher Website: http://www.oxfordjournals.org/

Journal: Molecular Biology and Evolutionsee more from them

Publication Website: http://mbe.oxfordjournals.org/

Volume: 34

Issue: 1

Extent: 131-144

Issue Date: 2016-10

pages:131-144Identifiers

Doi: https://doi.org/10.1093/molbev/msw228

Issn: 1537-1719

Uuid: uuid:c0f63cf1-4ba3-4969-8d3e-67d7a11c5f97

Urn: uri:c0f63cf1-4ba3-4969-8d3e-67d7a11c5f97

Pubs-id: pubs:667681 Item Description

Type: journal-article;

Language: eng Keywords: adaptation drug resistance effective population size plasmodium. rapid evolution soft selective sweep

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Autor: Anderson, TJC - - - Nair, S - - - McDew-White, M - - - Cheeseman, IH - - - Nkhoma, S - - - Bilgic, F - - - McGready, R - Oxford,

Fuente: https://ora.ox.ac.uk/objects/uuid:c0f63cf1-4ba3-4969-8d3e-67d7a11c5f97



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