Suppr超能文献

东南亚疟原虫中选定的及假定为中性的单核苷酸多态性的地理分布。

Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

作者信息

Anderson Tim J C, Nair Shalini, Sudimack Dan, Williams Jeff T, Mayxay Mayfong, Newton Paul N, Guthmann Jean-Paul, Smithuis Frank M, Tran Tinh Hien, van den Broek Ingrid V F, White Nicholas J, Nosten François

机构信息

Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.

出版信息

Mol Biol Evol. 2005 Dec;22(12):2362-74. doi: 10.1093/molbev/msi235. Epub 2005 Aug 10.

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.

摘要

与中性基因座相比,定向选择所靶向的基因座预计会呈现出更高的地理种群结构,最近有一系列论文利用这一原理来寻找参与适应性进化的基因组区域。对已知处于选择作用下的功能突变进行研究,对于评估这种方法的效用尤为有用。东南亚各国的抗疟药物治疗方案差异很大,这促使疟原虫中与耐药性相关的基因座发生了局部适应性进化。我们比较了4个已知参与抗疟药物耐药性的基因座中10个非同义突变(非同义单核苷酸多态性[nsSNPs])所揭示的种群结构,以及从东南亚6个国家的13个种群中收集的755份恶性疟原虫感染样本中,管家基因或功能未知基因中的10个同义突变(同义单核苷酸多态性[sSNPs])所揭示的模式。已知的与耐药性相关的nsSNPs的等位基因频率在不同地点之间存在显著差异(F(ST)=0.18 - 0.66),在泰国 - 缅甸边境频率最高,而在邻国老挝人民民主共和国频率最低。相比之下,我们发现10个sSNPs中的8个呈现出较弱但显著的地理结构(F(ST)=0 - 0.14)。重要的是,所有10个nsSNPs的F(ST)均显著高于基于假定中性的sSNPs中观察到的F(ST)值模拟出的中性预期(P < 8×10^(-5))。这一结果不受用于估计等位基因频率的方法或模拟中使用的种群数量的影响。鉴于现在已有恶性疟原虫的密集单核苷酸多态性(SNP)图谱和快速SNP检测方法,比较全基因组的遗传分化可能为识别疟原虫中与局部适应药物治疗方案或其他选择压力相关的基因座提供有价值的帮助。然而,恶性疟原虫基因组中似乎处于平衡选择(或与选择位点连锁)的多态性位点比例很高,这违背了选择位点罕见这一核心假设,这使得识别异常基因座变得复杂,并表明在使用这种方法时需要谨慎。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验