Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland.
Department of Natural Resource Sciences, McGill University, Montréal, Quebec, Canada.
BMC Genomics. 2020 Jan 6;21(1):17. doi: 10.1186/s12864-019-6415-5.
Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders.
In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine 4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine 27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes.
The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.
水蚤属物种通过涉及有性和无性繁殖的循环孤雌生殖进行繁殖。后代的性别由环境决定,并通过母体的内分泌信号传导。有趣的是,雄性和雌性水蚤在遗传上可以完全相同,但在行为、形态、寿命和代谢活性方面表现出很大的差异。我们的目标是整合多个组学数据集,包括在受控实验室条件下从遗传上相同的雌性和雄性水蚤 pulex 中生成的基因表达、剪接、组蛋白修饰和 DNA 甲基化数据,以更好地了解可能导致两性之间观察到的表型差异的潜在表观遗传因素。
在这项研究中,我们证明了基因表达水平与预测启动子区域的 DNA 甲基化和组蛋白 H3 赖氨酸 4 三甲基化(H3K4me3)的增加呈正相关。相反,整个转录长度上的组蛋白 H3 赖氨酸 27 三甲基化(H3K27me3)的升高与基因表达水平呈负相关。有趣的是,雄性水蚤主要被全局促进基因表达的表观遗传修饰所主导,而雌性水蚤则主要被全局降低基因表达的表观遗传修饰所主导。例如,与基因表达水平呈正相关的 CpG 甲基化在雄性水蚤中几乎所有差异甲基化位点都显著高于雌性水蚤。此外,与雌性水蚤相比,雄性水蚤中超过 3/4 的差异调控启动子中 H3K4me3 修饰水平更高。另一方面,与雄性水蚤相比,雌性水蚤中 H3K27me3 在超过 5/6 的差异修饰位点中更高。然而,两性都有大致相等数量的基因在一种性别中上调,而在另一种性别中下调。由于基因表达分析通常假设大多数基因在样本和不同条件下以相等的水平表达,因此无法检测到影响大多数基因的全局变化。
水蚤 pulex 中雄性和雌性之间的表观遗传差异巨大,主要由促进雄性水蚤中基因表达升高的变化所主导。此外,两性之间在基因表达变化和表观遗传修饰方面观察到的差异与与观察到的表型差异相关的生理途径有关。