Common host variation drives malaria parasite fitness in healthy human red cells.
Common host variation drives malaria parasite fitness in healthy human red cells.
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DOI：
10.7554/elife.69808
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发表时间：
2021-09-23
期刊：
影响因子：
7.7
通讯作者：
Egan ES
中科院分区：
文献类型：
--
作者：
Ebel ER;Kuypers FA;Lin C;Petrov DA;Egan ES
恶性疟原虫寄生虫在红细胞（RBC）内的复制导致人类严重疾病，特别是在非洲。众所周知，有害的等位基因如血红蛋白S可以赋予对疟疾的强大抵抗力，但常见的红细胞变异的影响在很大程度上尚未确定。在这里，我们收集了121名健康献血者的新鲜血液样本，其中大多数具有非洲血统，并进行了外显子组测序，详细的RBC表型分析和寄生虫适应性测定。超过三分之一的健康献血者在不知不觉中携带G6 PD缺乏症或血红蛋白病的等位基因，这些等位基因与特征性RBC表型相关。在非携带者中，红细胞水化、膜变形性和体积的变化与恶性疟原虫生长速率密切相关。PIEZO 1、SPTA 1/SPTB和几种恶性疟原虫侵袭受体的常见遗传变异也与寄生虫生长速率相关。有趣的是，我们观察到非洲人和欧洲人之间对非致病性RBC变异的分歧选择的证据很少或为阴性。这些发现表明了一个模型，其中全球广泛分布的中等数量的基因和表型的变化调节红细胞中的恶性疟原虫适应性。
The replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. Deleterious alleles like hemoglobin S are well-known to confer strong resistance to malaria, but the effects of common RBC variation are largely undetermined. Here, we collected fresh blood samples from 121 healthy donors, most with African ancestry, and performed exome sequencing, detailed RBC phenotyping, and parasite fitness assays. Over one-third of healthy donors unknowingly carried alleles for G6PD deficiency or hemoglobinopathies, which were associated with characteristic RBC phenotypes. Among non-carriers alone, variation in RBC hydration, membrane deformability, and volume was strongly associated with P. falciparum growth rate. Common genetic variants in PIEZO1, SPTA1/SPTB, and several P. falciparum invasion receptors were also associated with parasite growth rate. Interestingly, we observed little or negative evidence for divergent selection on non-pathogenic RBC variation between Africans and Europeans. These findings suggest a model in which globally widespread variation in a moderate number of genes and phenotypes modulates P. falciparum fitness in RBCs.
影响因子：
3.7
作者：
Tarazona-Santos E;Castilho L;Amaral DR;Costa DC;Furlani NG;Zuccherato LW;Machado M;Reid ME;Zalis MG;Rossit AR;Santos SE;Machado RL;Lustigman S
通讯作者：
Lustigman S