果蝇中DNA转座子捕获外源序列的机制及推动新基因起源的研究

DNA transposons are ubiquitous and major components of many eukaryotic genomes. They can cause genetic variations, and hence are commonly viewed as powerful facilitators of genome evolution. In plants, studies have shown that several types of DNA transposons have captured hundreds to thousands of host gene fragments, and carried them to re-transpose. However, there are only a few systematic surveys in animals. Moreover, the cases in plants are usually ancient and can hardly be used to infer the origination mechanism. In this proposal, we plan to detect the polymorphic host sequences captured by DNA transposons in Drosophila melanogaster populations based on the PacBio sequencing data. By analyzing the sequence properties which are not masked by secondary mutations, we try to build a new model to explain the formation of the chimeric structure. Then, we will investigate whether DNA transposons can produce new genes by functional genomics and evolutionary analysis. Our results will assist us in understanding the ability of capturing the host sequences by DNA transposons, and the origination of new genes mediated by DNA transposons in animals.

DNA转座子广泛存在于真核生物基因组中，它们可以引起各种遗传变异，是基因组进化的有力推动者。在植物中，大量例子表明DNA转座子可以捕获并携带宿主基因一起转座，然而在动物中相关报道还较少；而且植物中的例子都比较古老，很难用来推断产生的机制。本项目拟借助三代重测序数据在黑腹果蝇群体中寻找多态的DNA转座子捕获外源序列的事件，通过分析其尚未被后发突变所掩盖的序列特征，尝试建立一个新的模型来解释产生机制。同时通过功能基因组学和进化分析来考察DNA转座子捕获外源序列后能否形成新基因。本项目的研究结果将有助于理解在动物中DNA转座子捕获外源序列的能力，以及DNA转座子推动新基因起源的机制。

长期以来，转座子被认为是垃圾DNA，但是现在它们已被认为是演化重要的催化剂。此前在植物中发现MULE转座子捕获了上千个宿主基因或片段，形成重复基因，执行一定功能。然而其形成机制仍成谜，动物中也鲜有相关报道。我们搜索了100个动物基因组，鉴定了370个DNA转座子捕获外源序列的事件，并将其命名为Pack-TIR。对它们的序列特征分析发现了四个证据表明Pack-TIR的产生不依赖于转座子活性，符合缺口填补模型：Pack-TIR与DNA转座子数目成正相关关系；56.9%的Pack-TIR离母源序列很近；利用比较基因组学的方法，对灵长类动物的Pack-TIR进行了溯源，发现绝大多数是在转座子插入之后才被捕获；双链断裂的缺口较小且靠近转座子内部。在黑腹果蝇群体中找到的最年轻的多拷贝Ssk-FB4则符合新的FoSTeST模型：复制叉停滞-模板转换-转座。在功能层面，我们发现至少30%的Pack-TIR都可以转录，大部分与所在位点的基因融合。而Ssk-FB4则编码功能蛋白，有很强的选择信号和特定方向的快速演化，胞外区域氨基酸序列显著改变。由此证明了DNA转座子可以重塑基因结构，产生新基因。同时，我们在100个动物中鉴定了大量有活性的转座子，系统筛选开发载体工具，与睡美人等知名转座子类似，具有广阔的应用前景。