Laboratory of Pathogen Infection and Immunity, Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Laboratoire des Sciences Biomédicales, Alimentaires et Santé Environnementale, Département des Analyses Biomédicales, Ecole Supérieure des Techniques Biologiques et Alimentaires, Université de Lomé, Lomé, Togo.
Front Immunol. 2020 Oct 23;11:552698. doi: 10.3389/fimmu.2020.552698. eCollection 2020.
Malaria is a public health concern worldwide, and Togo has proven to be no exception. Effective approaches to provide information on biological insights for disease elimination are therefore a research priority. Local selection on malaria pathogens is due to multiple factors including host immunity. We undertook genome-wide analysis of sequence variation on a sample of 10 (Pf) clinical isolates from Togo to identify local-specific signals of selection. Paired-end short-read sequences were mapped and aligned onto > 95% of the 3D7 Pf reference genome sequence in high fold coverage. Data on 266 963 single nucleotide polymorphisms were obtained, with average nucleotide diversity π = 1.79 × 10. Both principal component and neighbor-joining tree analyses showed that the Togo parasites clustered according to their geographic (Africa) origin. In addition, the average genome-wide diversity of Pf from Togo was much higher than that from other African samples. Tajima's value of the Togo isolates was -0.56, suggesting evidence of directional selection and/or recent population expansion. Against this background, within-population analyses identifying loci of balancing and recent positive selections evidenced that host immunity has been the major selective agent. Importantly, 87 and 296 parasite antigen genes with Tajima's values > 1 and in the top 1% haplotype scores, respectively, include a significant representation of membrane proteins at the merozoite stage that invaded red blood cells (RBCs) and parasitized RBCs surface proteins that play roles in immunoevasion, adhesion, or rosetting. This is consistent with expectations that elevated signals of selection due to allele-specific acquired immunity are likely to operate on antigenic targets. Collectively, our data suggest a recent expansion of Pf population in Togo and evidence strong host immune selection on membrane/surface antigens reflected in signals of balancing/positive selection of important gene loci. Findings from this study provide a fundamental basis to engage studies for effective malaria control in Togo.
疟疾是全球公共卫生关注的问题，多哥也不例外。因此，提供有关消除疾病的生物学见解的信息的有效方法是研究重点。疟疾病原体的局部选择是由于多种因素，包括宿主免疫。我们对来自多哥的 10 个 Pf 临床分离株样本进行了全基因组序列变异分析，以确定选择的局部特定信号。通过将配对末端短读序列映射和比对到 3D7 Pf 参考基因组序列的 > 95%，获得了 266963 个单核苷酸多态性的数据，平均核苷酸多样性π=1.79×10-3。主成分和邻接树分析均表明，多哥寄生虫根据其地理（非洲）起源聚类。此外，来自多哥的 Pf 的平均全基因组多样性远高于其他非洲样本。多哥分离株的 Tajima 值为-0.56，表明存在定向选择和/或近期种群扩张的证据。在此背景下，识别平衡和近期正选择的基因座的群体内分析表明，宿主免疫一直是主要的选择因素。重要的是，87 个和 296 个寄生虫抗原基因的 Tajima 值分别大于 1 和最高 1%的单倍型评分，其中包括在入侵红细胞（RBC）的裂殖子阶段和在 RBC 表面蛋白上发挥免疫逃避、粘附或成环作用的膜蛋白的重要代表。这与预期一致，即由于等位基因特异性获得性免疫而导致的选择信号升高很可能作用于抗原靶标。总的来说，我们的数据表明，多哥 Pf 种群最近扩张，并且在膜/表面抗原上存在强烈的宿主免疫选择，反映在重要基因座的平衡/正选择信号中。这项研究的结果为在多哥进行有效的疟疾控制研究提供了基础。
