Ye Yixin H, Woolfit Megan, Huttley Gavin A, Rancès Edwige, Caragata Eric P, Popovici Jean, O'Neill Scott L, McGraw Elizabeth A
School of Biological Sciences, Monash University, Melbourne, Australia.
PLoS One. 2013 Jun 19;8(6):e66482. doi: 10.1371/journal.pone.0066482. Print 2013.
Cytosine methylation is one of several reversible epigenetic modifications of DNA that allow a greater flexibility in the relationship between genotype and phenotype. Methylation in the simplest models dampens gene expression by modifying regions of DNA critical for transcription factor binding. The capacity to methylate DNA is variable in the insects due to diverse histories of gene loss and duplication of DNA methylases. Mosquitoes like Drosophila melanogaster possess only a single methylase, DNMT2.
Here we characterise the methylome of the mosquito Aedes aegypti and examine its relationship to transcription and test the effects of infection with a virulent strain of the endosymbiont Wolbachia on the stability of methylation patterns.
We see that methylation in the A. aegypti genome is associated with reduced transcription and is most common in the promoters of genes relating to regulation of transcription and metabolism. Similar gene classes are also methylated in aphids and honeybees, suggesting either conservation or convergence of methylation patterns. In addition to this evidence of evolutionary stability, we also show that infection with the virulent wMelPop Wolbachia strain induces additional methylation and demethylation events in the genome. While most of these changes seem random with respect to gene function and have no detected effect on transcription, there does appear to be enrichment of genes associated with membrane function. Given that Wolbachia lives within a membrane-bound vacuole of host origin and retains a large number of genes for transporting host amino acids, inorganic ions and ATP despite a severely reduced genome, these changes might represent an evolved strategy for manipulating the host environments for its own gain. Testing for a direct link between these methylation changes and expression, however, will require study across a broader range of developmental stages and tissues with methods that detect splice variants.
胞嘧啶甲基化是DNA几种可逆的表观遗传修饰之一，它使基因型与表型之间的关系具有更大的灵活性。在最简单的模型中，甲基化通过修饰对转录因子结合至关重要的DNA区域来抑制基因表达。由于DNA甲基化酶基因丢失和复制的历史不同，昆虫中DNA甲基化的能力是可变的。像黑腹果蝇这样的蚊子只拥有一种甲基化酶，即DNMT2。
在这里，我们对埃及伊蚊的甲基化组进行了表征，并研究了其与转录的关系，还测试了感染内共生菌沃尔巴克氏体的强毒株对甲基化模式稳定性的影响。
我们发现埃及伊蚊基因组中的甲基化与转录减少有关，并且在与转录调控和代谢相关的基因启动子中最为常见。蚜虫和蜜蜂中也有类似的基因类群被甲基化，这表明甲基化模式要么是保守的，要么是趋同的。除了这种进化稳定性的证据外，我们还表明，感染强毒株wMelPop沃尔巴克氏体会在基因组中诱导额外的甲基化和去甲基化事件。虽然这些变化中的大多数在基因功能方面似乎是随机的，并且对转录没有检测到影响，但确实似乎有与膜功能相关的基因富集。鉴于沃尔巴克氏体生活在宿主来源的膜结合液泡中，并且尽管基因组严重减少，但仍保留了大量用于运输宿主氨基酸、无机离子和ATP的基因，这些变化可能代表了一种为自身利益而操纵宿主环境的进化策略。然而，要测试这些甲基化变化与表达之间的直接联系，需要使用检测剪接变体的方法，在更广泛的发育阶段和组织中进行研究。
