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    Jan 16, 2021
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    Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

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    Authors
    Anderson, T J C
    Nair, S
    Sudimack, D
    Williams, J T
    Mayxay, M
    Newton, P N
    Guthmann, J P
    Smithuis, F M
    Tran, T H
    van den Broek, I
    White, N J
    Nosten, F
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    Affiliation
    Southwest Foundation for Biomedical Research, San Antonio, Texas, USA. tanderso@darwin.sfbr.org
    Issue Date
    2005-12
    Submitted date
    2009-03-13
    
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    Journal
    Molecular Biology and Evolution
    Abstract
    Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach.
    URI
    http://hdl.handle.net/10144/66033
    DOI
    10.1093/molbev/msi235
    PubMed ID
    16093566
    Type
    Article
    Language
    en
    ISSN
    0737-4038
    Sponsors
    Epicentre
    ae974a485f413a2113503eed53cd6c53
    10.1093/molbev/msi235
    Scopus Count
    Collections
    Malaria

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