Mira-Martínez Sofía, van Schuppen Evi, Amambua-Ngwa Alfred, Bottieau Emmanuel, Affara Muna, Van Esbroeck Marjan, Vlieghe Erika, Guetens Pieter, Rovira-Graells Núria, Gómez-Pérez Gloria P, Alonso Pedro L, D'Alessandro Umberto, Rosanas-Urgell Anna, Cortés Alfred
Institute of Tropical Medicine, Antwerp, Belgium.
Barcelona Institute for Global Health (ISGlobal), Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
J Infect Dis. 2017 Mar 15;215(6):938-945. doi: 10.1093/infdis/jix053.
Many genes of the malaria parasite Plasmodium falciparum show clonally variant expression regulated at the epigenetic level. These genes participate in fundamental host-parasite interactions and contribute to adaptive processes. However, little is known about their expression patterns during human infections. A peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds.
We developed a procedure to characterize the expression of clag3 genes in naturally infected patients and in experimentally infected human volunteers.
We provide the first description of clag3 expression during human infections, which revealed mutually exclusive expression and identified the gene predominantly expressed. Adaptation to culture conditions or selection with a toxic compound resulted in isolate-dependent changes in clag3 expression. We also found that clag3 expression patterns were reset during transmission stages.
Different environment conditions select for parasites with different clag3 expression patterns, implying functional differences between the proteins encoded. The epigenetic memory is likely erased before parasites start infection of a new human host. Altogether, our findings support the idea that clonally variant genes facilitate the adaptation of parasite populations to changing conditions through bet-hedging strategies.
恶性疟原虫的许多基因表现出在表观遗传水平上受到调控的克隆变异表达。这些基因参与基本的宿主-寄生虫相互作用，并有助于适应性过程。然而，关于它们在人类感染期间的表达模式知之甚少。克隆变异基因的一个特殊例子是两个几乎相同的clag3基因，clag3.1和clag3.2，它们介导营养物质摄取并与对某些有毒化合物的抗性有关。
我们开发了一种程序来表征自然感染患者和实验感染人类志愿者中clag3基因的表达。
我们首次描述了人类感染期间clag3的表达，揭示了相互排斥的表达并确定了主要表达的基因。适应培养条件或用有毒化合物进行选择导致clag3表达的分离株依赖性变化。我们还发现clag3表达模式在传播阶段会重置。
不同的环境条件选择具有不同clag3表达模式的寄生虫，这意味着所编码蛋白质之间存在功能差异。在寄生虫开始感染新的人类宿主之前，表观遗传记忆可能被消除。总之，我们的研究结果支持这样一种观点，即克隆变异基因通过风险对冲策略促进寄生虫群体适应不断变化的条件。
