Transcriptional variation in the malaria parasite Plasmodium falciparum.
Transcriptional variation in the malaria parasite Plasmodium falciparum.
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DOI：
10.1101/gr.129692.111
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发表时间：
2012-05
期刊：
影响因子：
7
通讯作者：
Cortés A
中科院分区：
文献类型：
--
作者：
Rovira-Graells N;Gupta AP;Planet E;Crowley VM;Mok S;Ribas de Pouplana L;Preiser PR;Bozdech Z;Cortés A
疟疾遗传变异已被广泛表征，但表观遗传可塑性的水平在很大程度上仍未被探索。在这里，我们基于在均匀条件下生长的等基因疟原虫株系的高度精确的转录分析，提供了最致命的疟原虫恶性疟原虫转录变异的全面表征。该分析揭示了在遗传同质的无性系寄生虫种群中广泛的转录异质性。我们表明，在表观遗传水平上控制的克隆变异表达是特定基因和基因家族的固有特性，其中大多数参与宿主-寄生虫相互作用。内在的转录变异不仅局限于参与免疫逃避的基因，还影响与脂质代谢、蛋白质折叠、红细胞重塑或转录调节等相关的基因，这表明表观遗传变异会导致抗原和功能变异。我们观察到异染色质标记与克隆变异表达之间的普遍关联，将先前对特定基因的观察扩展到基本上所有变异表达的基因家族。这些结果表明，功能无关的恶性疟原虫基因家族的表型变异是由一种基于h3k9me3基异染色质可逆形成的共同机制介导的。在不断变化的环境中，多样性赋予种群适应性。我们的研究结果支持了恶性疟原虫使用一种下注对冲策略，作为定向转录反应的替代方案，以适应其环境中的常见波动。与这一观点一致的是，我们发现转录不同的等基因寄生虫系在模拟发热事件的热休克存活和适应周期性热休克方面存在显著差异，其模式与已有寄生虫的自然选择一致。
Malaria genetic variation has been extensively characterized, but the level of epigenetic plasticity remains largely unexplored. Here we provide a comprehensive characterization of transcriptional variation in the most lethal malaria parasite, Plasmodium falciparum, based on highly accurate transcriptional analysis of isogenic parasite lines grown under homogeneous conditions. This analysis revealed extensive transcriptional heterogeneity within genetically homogeneous clonal parasite populations. We show that clonally variant expression controlled at the epigenetic level is an intrinsic property of specific genes and gene families, the majority of which participate in host–parasite interactions. Intrinsic transcriptional variability is not restricted to genes involved in immune evasion, but also affects genes linked to lipid metabolism, protein folding, erythrocyte remodeling, or transcriptional regulation, among others, indicating that epigenetic variation results in both antigenic and functional variation. We observed a general association between heterochromatin marks and clonally variant expression, extending previous observations for specific genes to essentially all variantly expressed gene families. These results suggest that phenotypic variation of functionally unrelated P. falciparum gene families is mediated by a common mechanism based on reversible formation of H3K9me3-based heterochromatin. In changing environments, diversity confers fitness to a population. Our results support the idea that P. falciparum uses a bet-hedging strategy, as an alternative to directed transcriptional responses, to adapt to common fluctuations in its environment. Consistent with this idea, we found that transcriptionally different isogenic parasite lines markedly differed in their survival to heat-shock mimicking febrile episodes and adapted to periodic heat-shock with a pattern consistent with natural selection of pre-existing parasites.
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影响因子：
6.7
作者：
Ganesan K;Ponmee N;Jiang L;Fowble JW;White J;Kamchonwongpaisan S;Yuthavong Y;Wilairat P;Rathod PK
通讯作者：
Rathod PK
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
9.8
作者：
Gonzales JM;Patel JJ;Ponmee N;Jiang L;Tan A;Maher SP;Wuchty S;Rathod PK;Ferdig MT
通讯作者：
Ferdig MT
影响因子：
6.7
作者：
Cortés A;Carret C;Kaneko O;Yim Lim BY;Ivens A;Holder AA
通讯作者：
Holder AA
影响因子：
6.7
作者：
Campbell TL;De Silva EK;Olszewski KL;Elemento O;Llinás M
通讯作者：
Llinás M