近交衰退在动植物中普遍存在，是进化生物学领域的一个基础和核心的科学问题。关于近交衰退机制，几乎所有的研究结果都将它归结为基于DNA序列变化的遗传学机制。实际上，近交衰退中还有很多现象用遗传学改变不能解释。近几年来兴起和飞速发展的表观遗传学，让我们有机会从这个全新的角度理解近交衰退机制。家养动植物是理想材料，由于在品种培育中不断近交繁殖而呈现近交衰退现象。得益于家蚕种质材料的优势，我们能够建立研究近交衰退和其对应的杂交优势现象的材料模型。本项目正是计划以家蚕代表性品系不同近交程度亲本及其与另一亲本杂交后F1代为材料，系统比较甲基化组和转录组，揭示近交衰退和对应的杂交优势过程中基因组DNA甲基化格局及基因表达格局的差异，发掘一批可能与近交衰退和对应的杂交优势现象相关，同时受表观遗传学调控的基因，进而从表观遗传学新视角，开辟一条理解近交衰退的新途径。

Inbreeding depression is commonly observed in animals and plants and is a basic and core issue in evolutionary biology. Almost all of the research results on inbreeding depression mechanism attribute it to the genetic changes based on the DNA sequence. In fact, there are many phenomenon as to inbreeding depression that can not be explained by genetic changes. The rise and rapid development of epigenetics in recent years, giving us an opportunity to understand inbreeding depression mechanism from this new view. Domesticate is an ideal material, for its frequent inbreeding during stain improvements. Benefit from the advantages of silkworm germplasm, we are able to create a material model to explore the epigenetic mechanism on inbreeding depression and its corresponding phenomenon- heterosis. In this project，we plan to use 3 offspring populations from one silkworm strain with different extent of inbreeding, and a hybrid offspring population generated by crossing this stain to another one as material model. We will systematicaly comparing methylomes and transcriptomes among these materais, in order to reveal changes of methylation and gene expression patterns in the process of inbreeding depression and heterosis, indentify candidate genes influenced by epigenetic regulation and related to inbreeding depression and heterosis. Our outputs will open up a new perspective from epigenetics to understand inbreeding depression.

本项目主要研究家蚕近交衰退和杂交优势的表观遗传组学机制。项目实施过程中，我们根据实际情况对项目研究方案进行调整，着眼于杂种优势机制的探讨。研究发现，相对于近交后代，杂交优势后代在超亲性表达格局，尤其是超亲低表达的基因显著增加，这些基因富集在DNA复制以及细胞周期等过程。暗示杂交优势形成过程，该类基因调控机制可能具有重要作用。有趣的是，转录组分析发现TCA循环重要酶类也呈现超亲低表达。上述研究提示杂交优势的形成可能抑制细胞分化与碳水化合物代谢，而主要集中在蛋白质合成上。由于杂交优势是近代育种的重要手段，本项目拓展至家蚕-野蚕地方品种、家蚕改良品种的丝腺比较转录组以及基因组分析。研究结果显示蛋白质合成相关在改良品种中高表达，氨基酸合成通路在驯化和改良过程受到人工选择。有趣的是，研究发现TCA循环通路基因在日系改良品种显著下降而中系不明显，提示节约碳水化合物合成进而促进茧丝蛋白的合成可能是茧丝量提升的一种机制，并且该通路可能与杂交优势的形成有重要关系。最后，本项目利用CRISPR/Cas9系统得到家蚕薄茧突变体，为后续深入的功能研究及家蚕的遗传改造提供素材。