Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity.
Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity.
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DOI：
10.1093/molbev/msu106
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发表时间：
2014-06
影响因子：
10.7
通讯作者：
Conway DJ
中科院分区：
文献类型：
--
作者：
Mobegi VA;Duffy CW;Amambua-Ngwa A;Loua KM;Laman E;Nwakanma DC;MacInnis B;Aspeling-Jones H;Murray L;Clark TG;Kwiatkowski DP;Conway DJ
对病原体的局部不同选择可能是由于药物压力、宿主免疫力、宿主之间的传播机会或宿主内部基因型竞争强度的差异。在整个西非，人类疟原虫恶性疟原虫的高度重组种群是密切相关的，因为在这个流行地区，基因流动相对不受限制，但显著不同的生态和传播强度应造成明显的局部选择压力。对来自每年大部分时间都发生传播的几内亚共和国高流行地区的100株恶性疟原虫临床分离株样本进行了序列变异的全基因组分析，并与来自冈比亚先前取样人群的52株临床分离株的数据进行了比较，冈比亚的季节性疟疾传播相对有限。将配对末端短读序列与3D7恶性疟原虫参考基因组序列进行比对，获得136144个单核苷酸多态性（snp）数据。种群内分析确定了显示近期正向选择和平衡选择证据的位点，证实抗疟药物和宿主免疫是主要的选择因子。标准化综合单倍型评分反映的近期定向选择的许多特征是人群特异性的，包括由于各国历史上不同的抗疟药物使用而导致的耐药位点的差异。相反，这两个种群显示出一组相似的基因座，可能处于平衡选择下，如非常高的田岛D值所示，包括在侵入红细胞的裂殖子阶段表达的基因的显著过度代表和几个先前验证的获得性免疫靶点。种群间FST分析发现了少数位点的等位基因频率异常分化，最明显的是覆盖gdv1基因内部和两侧15kb区域的5个snp， gdv1基因调节配子细胞发育的早期阶段，这可能与蚊子媒介丰度和季节性的极端差异有关，而蚊子媒介丰度和季节性决定了寄生虫在性阶段的传播机会。
Locally varying selection on pathogens may be due to differences in drug pressure, host immunity, transmission opportunities between hosts, or the intensity of between-genotype competition within hosts. Highly recombining populations of the human malaria parasite Plasmodium falciparum throughout West Africa are closely related, as gene flow is relatively unrestricted in this endemic region, but markedly varying ecology and transmission intensity should cause distinct local selective pressures. Genome-wide analysis of sequence variation was undertaken on a sample of 100 P. falciparum clinical isolates from a highly endemic region of the Republic of Guinea where transmission occurs for most of each year and compared with data from 52 clinical isolates from a previously sampled population from The Gambia, where there is relatively limited seasonal malaria transmission. Paired-end short-read sequences were mapped against the 3D7 P. falciparum reference genome sequence, and data on 136,144 single nucleotide polymorphisms (SNPs) were obtained. Within-population analyses identifying loci showing evidence of recent positive directional selection and balancing selection confirm that antimalarial drugs and host immunity have been major selective agents. Many of the signatures of recent directional selection reflected by standardized integrated haplotype scores were population specific, including differences at drug resistance loci due to historically different antimalarial use between the countries. In contrast, both populations showed a similar set of loci likely to be under balancing selection as indicated by very high Tajima’s D values, including a significant overrepresentation of genes expressed at the merozoite stage that invades erythrocytes and several previously validated targets of acquired immunity. Between-population FST analysis identified exceptional differentiation of allele frequencies at a small number of loci, most markedly for five SNPs covering a 15-kb region within and flanking the gdv1 gene that regulates the early stages of gametocyte development, which is likely related to the extreme differences in mosquito vector abundance and seasonality that determine the transmission opportunities for the sexual stage of the parasite.
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影响因子：
10.7
作者：
Ochola LI;Tetteh KK;Stewart LB;Riitho V;Marsh K;Conway DJ
通讯作者：
Conway DJ
影响因子：
56.9
作者：
Joy, DA;Feng, XR;Su, XZ
通讯作者：
Su, XZ
DOI：
10.1016/s0169-4758(96)10077-6
发表时间：
1997-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Conway, DJ
通讯作者：
Conway, DJ
影响因子：
3.7
作者：
Auburn S;Campino S;Miotto O;Djimde AA;Zongo I;Manske M;Maslen G;Mangano V;Alcock D;MacInnis B;Rockett KA;Clark TG;Doumbo OK;Ouédraogo JB;Kwiatkowski DP
通讯作者：
Kwiatkowski DP
影响因子：
3.7
作者：
Ceesay, Serign J.;Casals-Pascual, Climent;Conway, David J.
通讯作者：
Conway, David J.