Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites
Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites
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DOI：
10.1186/s12864-020-6625-x
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发表时间：
2020-03-17
期刊：
影响因子：
4.4
通讯作者：
Merrick, Catherine J.
中科院分区：
文献类型：
--
作者：
Gage, Hunter L.;Merrick, Catherine J.
背景：疟原虫属的疟疾寄生虫编码几个家族的抗原编码基因。这些基因往往是高度可变的，高度重组和变异表达。最具特征的家族是var基因，仅在感染人类和类人猿的疟疾寄生虫的Laveranian亚属中发现。Var基因编码参与免疫逃避和维持慢性感染的主要毒力因子。在人类恶性疟原虫中，var基因重组和多样化似乎是由G-四链体（G4）DNA基序促进的，G4 DNA基序与恶性疟原虫中的var基因密切相关。在这里，我们研究了这种关联如何在疟原虫物种中进化-包括Laverania和更远的相关物种，这些物种缺乏var，但编码其他更古老的变异基因家族。var基因和G4形成基序之间的关联在Laverania中是保守的，跨越了近似100万年的进化时间，与暗示的证据进化的协会内发生的这一亚属。在啮齿类疟疾物种中，G4形成基序与PIR基因有一定的关联，但这在Laverania中并不保守，我们也没有发现这些基序与第二外群禽疟疾寄生虫中的任何基因家族有很强的关联。其次，我们比较了两种不同的G4预测算法在极其富含A/T的疟原虫基因组上的性能，并将这些预测与G4-seq的实验数据进行了比较，G4-seq是一种用于识别G4形成基序的DNA测序方法。我们发现了一个令人惊讶的缺乏一致性的两种算法之间的算法和G4-seq data.Conclusions：G4形成的图案是唯一的强烈相关的疟原虫变种基因，这表明G4的重组和多样化的这些基因的特殊作用。其次，在疟原虫物种的A/T丰富的基因组中，在研究这些重要的原生动物病原体中的G4时，预测算法的选择可能特别有影响力。
Background: The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species - both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families.Results: The association between var genes and G4-forming motifs was conserved across Laverania, spanning similar to 1 million years of evolutionary time, with suggestive evidence for evolution of the association occurring within this subgenus. In rodent malaria species, G4-forming motifs were somewhat associated with pir genes, but this was not conserved in the Laverania, nor did we find a strong association of these motifs with any gene family in a second outgroup of avian malaria parasites. Secondly, we compared two different G4 prediction algorithms in their performance on extremely A/T-rich Plasmodium genomes, and also compared these predictions with experimental data from G4-seq, a DNA sequencing method for identifying G4-forming motifs. We found a surprising lack of concordance between the two algorithms and also between the algorithms and G4-seq data.Conclusions: G4-forming motifs are uniquely strongly associated with Plasmodium var genes, suggesting a particular role for G4s in recombination and diversification of these genes. Secondly, in the A/T-rich genomes of Plasmodium species, the choice of prediction algorithm may be particularly influential when studying G4s in these important protozoan pathogens.