DNA transposons: evolutionary history and genomic impact in vertebrates

DNA 转座子：脊椎动物的进化史和基因组影响

• 批准号: 8297913
• 负责人: Cedric Feschotte
• 金额: $ 17.04万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8297913
• 关键词: Accounting; Architecture; Automobile Driving; Beryllium; Bioinformatics; Biological; Biology; Biomedical Research; Cataloging; Catalogs; Chiroptera; Code; Complement; DNA Sequence; DNA Sequence Rearrangement; DNA Transposable Elements; DNA Transposons; Data Set; Development; Elements; Eukaryota; Event; Evolution; Exons; Family; Fostering; Frequencies; Gene Expression Profile; Genes; Genetic Materials; Genome; Genome Scan; Genome Stability; Genomics; Human; Human Genome; Incidence Study; Indium; Left; Liver; Mammals; Measures; Mediating; Mining; Mobile Genetic Elements; Modeling; Mus; Nature; Organism; Pattern; Positioning Attribute; Process; Property; Proteins; RNA; Radiation; Recording of previous events; Regulatory Element; Research; Resources; Retrotransposon; Shapes; Structure; Surveys; System; Testis; Time; Transcript; Variant; Vertebrates; brain tissue; comparative genomics; design; genome sequencing; genome-wide; human disease; innovation; mammalian genome; next generation; novel; structural genomics; transposon/insertion element

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. PUBLIC HEALTH RELEVANCE: In mammalian genomes, including our own, DNA transposons occupy more space than protein-coding sequences. Yet we know surprisingly little about the biology and significance of this class of mobile genetic elements. Here we take advantage of recent breakthroughs in DNA sequencing and bioinformatics to study when and how DNA transposons manage to cross species boundaries via horizontal transfer and how their invasions impact the structure and expression of the mammalian genome.

描述（申请人提供）：移动的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。移动的元件的插入和重排对基因组的稳定性构成了严重的威胁，事实上，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的因素在塑造基因组和促进生物新奇出现方面的长期影响。但我们对哺乳动物中移动的元素的生物学和影响仍然有一个不完整和有偏见的了解。这是因为大多数研究都集中在反转录转座子上，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件，DNA转座子，这在哺乳动物中仍然研究不足。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转座子是通过水平转移（非交配物种之间的遗传物质传递）引入不同哺乳动物的。由于最近在DNA测序和生物信息学方面的技术进步，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，以获得定量评估的频率和广度的水平转座子转移脊椎动物。移动的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，我们利用蝙蝠中最近和大规模DNA转座子入侵的发现，首次在任何生物体中研究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。蝙蝠作为一种哺乳动物系统来研究DNA转座子和基因组进化是创新的，它将有助于为这些新兴的生物医学研究模型提供越来越多的基因组资源。 公共卫生相关性：在哺乳动物的基因组中，包括我们自己的基因组，DNA转座子比蛋白质编码序列占据更多的空间。然而，令人惊讶的是，我们对这类移动的遗传元件的生物学和意义知之甚少。在这里，我们利用DNA测序和生物信息学的最新突破，研究DNA转座子何时以及如何通过水平转移跨越物种边界，以及它们的入侵如何影响哺乳动物基因组的结构和表达。