Impact of transposable elements during animal regeneration

再生能力在不同的多细胞生物体中差异很大。对其潜在的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，而对非编码基因组的研究最近成为焦点。转座元件(转座子)构成非编码序列的最大部分。最近的数据显示，特定的转座子在再生过程中被激活。有趣的是，在进化的时间尺度上，转座子可以促成许多具有非凡再生能力的物种特有的大基因组大小。这是转座子活性和插入率提高的结果，转座子对其插入或缺失的细胞防御，以及给定的种群结构和选择压力在长期尺度上平衡了转座子的维持或缺失。结合它们在基因组稳定性和调控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的再生能力的潜在进化驱动力的关键但仍未回答的问题。这项提议将在两个关键的、具有系统发育信息的再生模式系统中比较转座子在再生过程中的转录动态及其对基因组结构的影响。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，首次在亚家族分辨率水平上提供再生活性元件的完整概述。然后，我们将研究转座子在再生组织中的细胞水平活性，并从功能上测试它们在体内的作用。最后，我们将研究全基因组转座子在连续再生组织中的插入动力学，例如在水龙的解离-重组实验或Axolot1的连续肢体再生过程中的重复再生周期。这项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过程中的功能以及在每个再生周期中基因组受到的影响程度，包括发育和进化两个时间尺度。这些数据将为基因组的稳定性、响应以及对其结构的修改提供关键的见解，例如基因组中是否存在任何与再生相关的热点。

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.