Journal Article > ResearchFull Text
Mol Biol Evol. 2005 December 1; Volume 22 (Issue 12); DOI:10.1093/molbev/msi235
Anderson TJC, Nair SA, Sudimack D, Williams JT, Mayxay M, et al.
Mol Biol Evol. 2005 December 1; Volume 22 (Issue 12); DOI:10.1093/molbev/msi235
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.
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Mol Biol Evol. 2024 November 26; Volume 2877; 3-24.; DOI:10.1007/978-1-0716-4256-6_1
Sprecher A, Van Herp M
Mol Biol Evol. 2024 November 26; Volume 2877; 3-24.; DOI:10.1007/978-1-0716-4256-6_1
In many ways, Marburg virus disease resembles the more well-known Ebola virus disease: The clinical syndrome is similar, management of outbreaks is similar, and the fear engendered in the population experiencing the outbreak is similar. However, diagnostics, therapeutics, and vaccines to manage patients and outbreaks are not similarly available. These have been developed but not yet approved, as outbreaks have not provided the opportunity to establish an evidence base for regulators to evaluate their use in humans. The history of outbreaks of Marburg virus disease suggests that this opportunity will not come, and so alternative pathways to regulatory approval are needed.