The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni.
The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni.
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DOI：
10.1371/journal.pntd.0005246
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发表时间：
2017-05
影响因子：
3.8
通讯作者：
Hoffmann KF
中科院分区：
文献类型：
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作者：
Geyer KK;Niazi UH;Duval D;Cosseau C;Tomlinson C;Chalmers IW;Swain MT;Cutress DJ;Bickham-Wright U;Munshi SE;Grunau C;Yoshino TP;Hoffmann KF
使人衰弱的血吸虫病是由寄生虫感染引起的，寄生虫在最终宿主（人）和中间宿主（蜗牛）之间保持复杂的生命周期。虽然人们对最终宿主如何对血吸虫感染做出反应了解很多，但描述蜗牛对感染的反应的信息相对较少。在这里，使用最近通过对双脐螺中间宿主基因组测序所揭示的信息，我们提供的证据表明，预测的核心蜗牛DNA甲基化机制组件与种内繁殖过程和种间相互作用有关。首先，甲基-CpG结合域蛋白（Bgmbd 2/3）和DNA甲基转移酶1（Bgdnmt 1）基因在性腺中的转录富集相比，体细胞组织与5-氮杂胞苷（5-AzaC）处理显着抑制产卵。其次，与近交系（NMRI）- B相比，有色杂种中5-甲基胞嘧啶（5 mC）、DNA甲基转移酶活性和5 mC结合水平升高。glabrata种群表明蜗牛的DNA甲基化机制在维持杂种优势或杂种优势中的作用。第三，通过亚硫酸氢盐（BS）-PCR对5 mC的基因座特异性检测揭示了管家蛋白编码基因（Bg 14 -3-3）的外显子区域内的5 mC，支持了该物种基因组的先前计算机预测和全基因组BS-Seq分析。最后，我们提供了寄生虫介导的宿主表观遗传重编程的初步证据，如Bge（B. glabrata胚胎细胞系）暴露于寄生虫幼虫转化产物（LTP）。B中存在功能性DNA甲基化机制。glabrata以及这些基因产物的调制在响应于寄生虫产物，表明在蜗牛发育/产卵和寄生虫相互作用的DNA甲基化的重要作用。进一步破译这一表观遗传过程中的作用Biomphalaria/血吸虫的共同进化生物学可能会揭示与疾病传播相关的关键因素，此外，使新的生命周期干预策略的发现。双脐螺属的成员代表了具有重要医学意义的呼吸空气（肺状）水生腹足类软体动物。大多数物种都是吸虫类扁虫曼氏血吸虫的强制性中间宿主，曼氏血吸虫是一种导致毁灭性的被忽视的热带疾病血吸虫病的病原体。由于这种疾病的传播受其软体动物宿主的温度耐受性的控制，预计全球气温的上升将使这种蜗牛进一步从原生范围扩展到温带地区。虽然血吸虫病目前主要通过吡喹酮介导的感染个体化疗来控制，但从长远来看，需要新的策略。新的光滑双脐螺基因组的可用性，现在重要的是，使下一代血吸虫病控制策略的设计集中在中间宿主。在这里，使用各种不同的方法，我们在功能上解释了B中至关重要的分子过程DNA甲基化。glabrata，这是介导的一套生物参与者，并参与了广泛的后生动物的功能。重要的是，我们使用全局和位点特异性方法证实了蜗牛基因组中存在5 mC，并且我们进一步提供了S. mansoni引起的调节中间体的宿主DNA甲基化系统。
The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail’s response to infection. Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA methyltransferase activity and 5mC binding in pigmented hybrid- compared to inbred (NMRI)- B. glabrata populations indicate a role for the snail’s DNA methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus-specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in silico predictions and whole genome BS-Seq analysis of this species’ genome. Finally, we provide preliminary evidence for parasite-mediated host epigenetic reprogramming in the schistosome/snail system, as demonstrated by the increase in Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic cell line) exposure to parasite larval transformation products (LTP). The presence of a functional DNA methylation machinery in B. glabrata as well as the modulation of these gene products in response to schistosome products, suggests a vital role for DNA methylation during snail development/oviposition and parasite interactions. Further deciphering the role of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary biology may reveal key factors associated with disease transmission and, moreover, enable the discovery of novel lifecycle intervention strategies. Members of the genus Biomphalaria represent air-breathing (pulmonate) aquatic gastropod molluscs of great medical importance. The majority of species are obligatory intermediate hosts of the trematode flatworm Schistosoma mansoni, a pathogen responsible for the devastating neglected tropical disease schistosomiasis. Since the spread of the disease is governed by the temperature tolerance of its molluscan host, the envisaged rise in global temperatures will allow for the further expansion of the snail outside the native range into temperate regions. While schistosomiasis is currently predominantly controlled by praziquantel-mediated chemotherapy of infected individuals, novel strategies are needed in the longer term. The availability of the new Biomphalaria glabrata genome importantly now enables the design of next-generation schistosomiasis control strategies focused on the intermediate host. Here, using a variety of diverse approaches, we functionally characterise the critically important molecular process DNA methylation in B. glabrata, which is mediated by a suite of biological participants and is involved in a wide range of metazoan functions. Importantly, we confirm the presence of 5mC within the snail’s genome using global as well as locus-specific methodologies and we further provide the first evidence for a S. mansoni-provoked modulation of the intermediate’s host DNA methylation system.