转座元件介导的表观调控和序列变异在动物低氧适应中的作用

The transposable element is a class of DNA fragments that can be moved in the genome. Because their contents are very high (especially in some large genomes), their functions and effects on the evolution of the host genome have always been a problem that people are just trying to solve. With the development of technology of molecular genetics as well as the omics, people gradually realize that transposable elements are in fact the main carrier of epigenetic markers and catalyzer of the structural variation in the genome. Meanwhile, it has been found that the transposition is likely to have a beneficial impact on the host, such as providing important regulatory elements for host genes, or domesticated to be new genes of the host. In order to further study the transposable element in the host adaptive evolution, in this project, we are planning to use animals' hypoxia adaptation as a starting point, with a number of animal groups as the research object as well as the comprehensive analyses of genomics, transcriptomics, epigenetic genomics, and cell function validation mechanism, to illustrate the effects of sequence variation that are mediated by transposable element. From this study, we hope to provide a clue for further understanding the high proportion of repeat sequences in animal genome and wish to provide a new perspective for studying animals' hypoxia adaptation.

转座元件是基因组内一类可移动的DNA片段。由于其含量非常高（尤其是在一些较大的基因组中），它们的功能以及对宿主基因组的进化所产生的影响一直是人们致力于解决的问题。随着分子遗传学和组学技术的发展，人们逐渐认识到转座元件其实是基因组内主要的表观遗传标记“承载体”以及结构变异的“催化剂”，并且发现很多转座后的DNA序列能为宿主基因带来有利影响，如提供重要的调控元件，或“驯化”成宿主的新基因等。为了进一步研究转座元件在宿主的适应性进化中的作用，本项目以动物的低氧适应这一具有战略意义的研究为切入点，以多个动物类群为研究对象（如高山倭蛙、青海沙蜥），通过群体基因组、转录组学分析、表观遗传组学和小RNA的联合分析，及细胞功能验证，系统阐明由转座元件介导的序列变异和表观调控在动物低氧适应中的作用及其分子机制，为理解动物基因组中为何存在如此高比例的转座元件提供一定思路，也为拓展低氧适应的研究提供新的视角。

转座元件（Transposable elements）是基因组内一类可以移动的DNA片段。DNA测序技术的发展使得越来越多的物种的基因组信息被破译。TE几乎存在于所有的物种中，尤其是两栖类中基因组存在有大量的TE，但基因的数目并不比其他动物多。我们以高山倭蛙（Nanorana parkeri）为研究体系，基于进化分析解析了该物种的高原适应机制，同时发现高山倭蛙中大部分的TE的含量和TE的分歧度呈现显著的负相关。表明高山倭蛙中的TE可能都是年轻的TE，而非古老的TE。在东部高山倭蛙群体中鉴定出33055个PTE（Polymorphic TE），PTE的数量和LD呈现显著正相关。表明PTE在基因组内的分布模式可能受到连锁不平衡的影响。同时发现，PTE并未带来周边基因组甲基化水平的变化（methylation spreading）。受选择的PTE相关的基因与高原适应相关，例如参与到血管生成调控的SEMA6A基因在高低海拔之间存在表达差异。我们阐释了由转座元件介导的序列变异在高山倭蛙高原适应中扮演的角色及其作用机制。