Function and evolution of DNA methylation in Nasonia vitripennis.
Function and evolution of DNA methylation in Nasonia vitripennis.
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DOI：
10.1371/journal.pgen.1003872
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Werren JH
中科院分区：
文献类型：
--
作者：
Wang X;Wheeler D;Avery A;Rago A;Choi JH;Colbourne JK;Clark AG;Werren JH
丽翅蜂是一种新兴的DNA甲基化功能分析的遗传模型。在这里，我们在碱基对分辨率的全基因组甲基化的特点，并比较这些结果的基因表达在五个发育阶段和甲基化模式在其他昆虫报道。使用来自高度近交系的成年雌性的亚硫酸氢盐测序来完成整个基因组的DNA甲基化的准确评估。三分之一的基因在基因体上表现出广泛的甲基化，但甲基化的DNA在非编码区中没有发现，在转座子中也很少。甲基化基因在整个基因组中以小簇的形式出现。甲基化划分了外显子-内含子的边界，在外显子上甲基化水平升高，主要在基因的5′区域。它在翻译起始和终止位点附近也升高，在5′和3′ UTR中水平降低。与非甲基化基因相比，甲基化基因在发育阶段具有更高的中值表达水平和更低的表达变异。甲基化和非甲基化基因之间的差异剪接频率没有差异，并且在Nasonia中尚未确定甲基化在调节选择性剪接中的作用。系统发育比较表明，许多基因在很长的进化时间尺度上保持甲基化状态。Nasonia甲基化基因在昆虫中更可能是保守的，但即使是那些不保守的基因也比可比的非甲基化基因在发育过程中表现出更广泛的表达。最后，对重复基因的检查显示，在基因重复后在Nasonia谱系中失去甲基化的那些旁系同源物进化得更快，显示出降低的中值表达水平，并且在整个发育过程中表达的特化增加。Nasonia基因的甲基化信号在发育阶段的组成型转录，而非甲基化基因显示出更动态的发育表达模式。我们推测甲基化的丧失可能导致进化中的发育特化增加，甲基化的获得可能导致更广泛的组成型表达。昆虫使用甲基化以与脊椎动物不同的方式调节基因组功能。在这里，我们量化的全球甲基化谱的寄生蜂物种，丽翅蜂，一个模型，具有一些优势，蚂蚁和蜜蜂的功能和遗传分析的甲基化，如短世代时间，近交系，和互育物种。使用高度近交系使我们能够精确地表征DNA甲基化，将其与发育阶段的基因表达变化进行比较，并与其他昆虫物种进行对比。DNA甲基化几乎只发生在5′端1 kbp的编码外显子上，约1/3的蛋白质编码基因发生甲基化。甲基化基因往往出现在基因组中的小簇中。与许多生物不同，纳索尼亚几乎所有的转座因子基因都没有甲基化。甲基化基因在发育阶段表现出更均匀的表达，中度和高度表达的基因，这表明DNA甲基化标记的基因组成型表达。在成对的差异甲基化重复基因中，在Nasonia谱系中重复后失去DNA甲基化的旁系同源物显示出较低的表达和更高的表达特化。最后，通过比较分析，我们发现甲基化基因在进化过程中的三个不同的时间尺度上更加保守。
The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression. Insects use methylation to modulate genome function in a different manner from vertebrates. Here, we quantified the global methylation profile in a parasitic wasp species, Nasonia vitripennis, a model with some advantages over ant and honeybee for functional and genetic analyses of methylation, such as short generation time, inbred lines, and inter-fertile species. Using a highly inbred line permitted us to precisely characterize DNA methylation, which is compared to gene expression variation across developmental stages, and contrasted to other insect species. DNA methylation is almost exclusively on the 5′-most 1 kbp coding exons, and ∼1/3 of protein coding genes are methylated. Methylated genes tend to occur in small clusters in the genome. Unlike many organisms, Nasonia leaves nearly all transposable element genes non-methylated. Methylated genes exhibit more uniform expression across developmental stages for both moderately and highly expressed genes, suggesting that DNA methylation is marking the genes for constitutive expression. Among pairs of differentially methylated duplicated genes, the paralogs that lose DNA methylation after duplication in the Nasonia lineage show lower expression and greater specialization of expression. Finally, by comparative analysis, we show that methylated genes are more conserved at three different time scales during evolution.
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影响因子：
4.4
作者：
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12.3
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通讯作者：
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