DNA transposons: evolutionary history and genomic impact in vertebrates

描述（申请人提供）：移动DNA元件是哺乳动物基因组的主要组成部分，约占其遗传物质的一半。可移动元件的插入和重排对基因组的稳定性构成严重威胁，实际上它们与一百多种人类疾病有关。近年来，人们越来越认识到移动元件在塑造基因组和促进生物新颖性出现方面的长期影响。但是我们对哺乳动物中活动元素的生物学和影响仍然有一个不完整和有偏见的图景。这是因为大多数研究都集中在逆转录转座子上，这是人类和小鼠中的一类重要元素。在这次更新中，我们将继续研究另一类广泛存在的元素，DNA转座子，这在哺乳动物中仍未得到充分研究。DNA转座子占人类基因组的3%，至少占蝙蝠基因组的12%。它们在生物学和进化动力学的许多方面与反转录转座子不同。例如，我们发现一些DNA转座子通过水平转移的方式被引入到不同的哺乳动物中，即在非交配物种之间传递遗传物质。由于DNA测序和生物信息学的最新技术进步，我们现在能够在全基因组范围内研究DNA转座子入侵的发生率和后果。在第一个目标中，我们将采用计算和实验相结合的方法来获得脊椎动物水平转座子转移的频率和广度的定量评估。移动元素的水平转移是细菌进化的重要机制。我们的研究应该阐明它在脊椎动物中的进化意义。在第二个和第三个目标中，我们利用最近在蝙蝠中发现的大量DNA转座子入侵，首次在任何生物体中检查DNA转座子对基因组结构变异（目标2）和转录组进化（目标3）的贡献。蝙蝠作为哺乳动物系统来研究DNA转座子和基因组进化是一种创新，它将为这些新兴的生物医学研究模式提供越来越多的基因组资源。

DESCRIPTION (provided by applicant): Mobile DNA elements are major components of mammalian genomes, accounting for about half of their genetic material. Insertion and rearrangements of mobile elements poses a serious threat to genome stability, and indeed they have been tied to over a hundred human diseases. In recent years there has been a growing appreciation of the long-term influence of mobile elements in shaping genomes and fostering the emergence of biological novelty. But we still have an incomplete and biased picture of the biology and impact of mobile elements in mammals. This is because most of the research has focused on retrotransposons, a prominent class of elements in human and mouse. In this renewal we will pursue our study of another widespread class of elements, the DNA transposons, which remains understudied in mammals. DNA transposons account for 3% of the human genome and at least 12% of the bat genome. They are distinguished from retrotransposons by many facets of their biology and evolutionary dynamics. For instance, we found that some DNA transposons were introduced in diverse mammals by means of horizontal transfer, the passage of genetic material between non-mating species. Thanks to recent technological advances in DNA sequencing and bioinformatics, we are now well positioned to study the incidence and consequences of DNA transposon invasions at a genome-wide scale. In the first aim we will employ a combination of computational and experimental approaches to obtain a quantitative assessment of the frequency and breadth of horizontal transposon transfers in vertebrates. Horizontal transfer of mobile elements is a crucial mechanism for bacterial evolution. Our studies should clarify its evolutionary significance in vertebrates. In th second and third aims we capitalize on the discovery of recent and massive DNA transposon invasions in bats to examine, for the first time in any organism, the contribution of DNA transposons to genomic structural variation (Aim 2) and transcriptome evolution (Aim 3). The development of bats as a mammalian system to study DNA transposons and genome evolution is innovative and it will contribute to a growing body of genomic resources for these emerging models in biomedical research.