Impact of transposable elements during animal regeneration

转座元件对动物再生过程的影响

• 批准号: 427970843
• 负责人: Professor Dr. Thomas W. Holstein
• 金额: --
• 依托单位: IMBA - Institute of Molecular Biotechnology GmbH
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/427970843?language=en
• 关键词: Impact; transposable; elements; during; animal

Regeneration capabilities vary significantly across multicellular organisms. Studies on the underlying molecular mechanisms and their evolution have largely focused on deciphering the coding gene complement in various model systems with studies of the non-coding genome recently coming into focus. Transposable elements (transposons) comprise the largest portion of the non-coding sequence. Recent data shows that specific transposons are activated during regeneration. Interestingly, on an evolutionary time-scale, transposons can contribute to the characteristic large genome size of many species with extraordinary regeneration capabilities. This is a result of both elevated activity and insertion rate of transposons, cellular defenses against their insertions or deletions, as well as the given population structure and selective pressures that in the long time-scale balances their maintenance or deletion. Combined with their known role in genome stability and generation of regulatory novelty those insights pose key yet still unanswered questions regarding the role of transposons both during the actual process of regeneration as well as a potential evolutionary drive to evolve sophisticated regenerative capabilities.This proposal will compare the transcriptional dynamics of transposons during regeneration and their effect on the genome architecture in two key, phylogenetically informative model systems for regeneration, the cnidarian Hydra magnipapillata and the vertebrate, salamander, Ambystoma mexicanum (axolotl). We will characterize the shared and derived transcriptionally active transposable elements among those two species, providing the first complete overview of regeneration-active elements at the sub-family resolution level. We will then study cellular-level activity of transposons in regenerating tissues and functionally test their role in vivo. We will finally study genome-wide transposon insertion dynamics in consecutively regenerating tissues, such as in the repeated cycles of regeneration during dissociation-reaggregation experiments in hydra or consecutive limb regeneration in axolotl. This experiment will allow us to investigate, on the genome-wide scale, transposon insertion patterns and their effect on core genes involved in injury response and tissue regeneration.Such data will reveal, for the first time, the functional repertoire of transposons during regeneration and the extent to which the genomes are affected during each regenerative cycle, encompassing both developmental and evolutionary time-scales. The data will provide crucial insights into the genome stability, response, as well as modifications to its structure such as the presence of any regeneration-linked hotspots in the genome.

不同多细胞生物体的再生能力差异很大。对潜在分子机制及其进化的研究主要集中在破译各种模型系统中的编码基因补体，最近对非编码基因组的研究成为焦点。转座元件（转座子）构成非编码序列的最大部分。最近的数据表明，特定的转座子在再生过程中被激活。有趣的是，在进化时间尺度上，转座子可以为许多具有非凡再生能力的物种带来特征性的大基因组大小。这是转座子活性和插入率升高、针对其插入或缺失的细胞防御、以及在长时间尺度内平衡其维持或缺失的给定群体结构和选择压力的结果。结合它们在基因组稳定性和监管新颖性产生中的已知作用，这些见解提出了关于转座子在实际再生过程中的作用以及进化复杂再生能力的潜在进化驱动力的关键但仍未解答的问题。该提案将比较再生过程中转座子的转录动力学及其对两个关键的、系统发育信息丰富的再生模型系统（刺胞动物水螅和脊椎动物蝾螈）中基因组结构的影响，墨西哥钝口螈（axolotl）。我们将描述这两个物种之间共享和衍生的转录活性转座元件的特征，提供亚科分辨率水平上再生活性元件的第一个完整概述。然后，我们将研究再生组织中转座子的细胞水平活性，并对其在体内的作用进行功能测试。我们最终将研究连续再生组织中的全基因组转座子插入动力学，例如水螅解离重聚集实验期间的重复再生循环或蝾螈的连续肢体再生。该实验将使我们能够在全基因组范围内研究转座子插入模式及其对参与损伤反应和组织再生的核心基因的影响。这些数据将首次揭示转座子在再生和组织再生过程中的功能库。基因组在每个再生周期中受到影响的程度，包括发育和进化时间尺度。这些数据将为基因组稳定性、反应及其结构修改提供重要见解，例如基因组中是否存在任何与再生相关的热点。