Roles of DNA mobile elements in primate genomes

DNA可移动元件，也称为转座元件或转座子，是指可以从基因组中的一个位置移动或复制到另一个位置的DNA元件。它们存在于从细菌到人类的大多数生物的基因组中，在一些植物和动物的基因组中占比高达85%。在人类基因组中，超过50%的DNA序列由可移动元件组成，这些可移动元件由来自许多可移动元件家族和亚家族的500多万个单独元件组成。尽管曾经被认为是“垃圾DNA”，但现在人们已经知道，可移动元素在塑造物种基因组进化和通过过多的分子机制促进特定基因功能方面发挥着重要作用。然而，它们对基因组进化和基因功能的影响程度以及它们的具体机制，特别是以物种特有的方式影响的程度，仍然是未知的。*在未来五年，我们的目标是以灵长类动物，特别是人类为模型，加深我们对移动元素的理解。作为被研究得最好的生物，人类拥有最好的参考基因组和基因注释质量，以及大量个人基因组的可用性，人类是我们研究问题的理想模型。许多其他与人类关系密切的灵长类物种的基因组序列最近也出现了。这使我们能够进行物种间和物种内的比较基因组研究。具体地说，我们将首先通过比较基因组学的方法，以物种特有的方式检查至少八个灵长类物种在移动元素组成、位置和对基因功能的潜在影响方面的差异。然后，我们将详细研究人类基因组中的可移动元件，以检查它们在人类进化过程中的图谱变化，对人类个体遗传多态的贡献，以及对人类转录本的参与。我们将继续维护/更新我们的旗舰数据库DBRIP，该数据库记录了来自移动元素插入的遗传多态。此外，我们的目标是提供人类移动元件变异的完整序列特征，并开发生物信息学资源，以提供更精简和准确的个人基因组分析。*在解决这些重要的生物学问题的同时，拟议的研究还将为基因组学/遗传学研究社区建立宝贵的资源。他们还将开展多学科合作，并在基因组学和生物信息学等要求很高的领域提供HQP培训。

DNA mobile elements, also called transposable elements or transposons, are DNA elements that can move or copy from one location to another in the genomes. They exist in the genomes of most organisms from bacteria to humans, and constitute as much as 85% in some plant and animal genomes. In the human genome, more than 50% of the DNA sequences are comprised of mobile elements, which are represented by more than 5 million individual elements from many families and subfamilies of mobile elements. Although once considered as “Junk DNA”, mobile elements are now known to play important roles in shaping the genome evolution of species and in contributing to specific gene functions through a plethora of molecular mechanisms. However, much is still unknown about the degree of their impact on genome evolution and gene function, as well as their specific mechanisms, especially in a species-specific fashion. ******In the next five years, we aim to further our understanding of mobile elements using primates, especially human, as models. As the best-studied organism with the best quality of a reference genome and gene annotation, as well as the availability of a large number of personal genomes, the human serves as an ideal model for our research questions. The genome sequences of many other primate species closely related to human have also become available recently. This permits us to perform both inter- and intra-species comparative genomic studies. Specifically, we will first examine the differences in mobile element compositions, location, and potential impact on gene functions in a species-specific fashion for at least eight primate species through a comparative genomic approach. We will then study the mobile elements in the human genome in detail to examine their profile changes during human evolution, contribution to genetic polymorphism among human individuals, and participation in the human transcriptomes. We will continue to maintain/update our flagship dbRIP database, which documents the genetic polymorphisms derived from mobile element insertions. Further, we aim to provide complete sequence characterization of mobile element variants in humans and develop bioinformatics resources to provide more streamlined and accurate personal genome analysis.******While addressing these important biological questions, the proposed studies will also build valuable resources for the genomics/genetic research communities. They will also develop multi-disciplinary collaborations and provide HQP training in the highly demanded areas of genomics and bioinformatics.