RUI: Origins of Intron-Exon Structures

该研究项目研究了从人类到寄生虫等大范围生物的基因和基因组分子结构的差异。特别是，该项目试图回答内含子起源的谜团，内含子是介于DNA片段之间的，它干扰了所有真核生物的基因，即拥有有核细胞的有机体。通过在美国最多元化的综合性大学之一旧金山州立大学开展这项工作，这项工作将支持在职业生涯早期(本科生和硕士学生)对代表人数较少的少数群体的个人进行生物和计算科学方面的培训。该项目试图解答真核生物剪接体内含子起源的谜团。绝大多数内含子是插入到蛋白质编码基因中的DNA片段，没有已知的功能，具有准随机的DNA序列，这引发了两个问题：(I)为什么会有内含子；(Ii)内含子是如何在进化中产生的？为了回答这些问题，该项目使用了识别和研究最近内含子获得(内含子的产生)和丢失(内含子从基因组中删除)的策略。最近的收获和损失将通过对50组密切相关的生物体进行全基因组直接比较，以及通过比较更大的1000种生物体基因组中的单个内含子序列来确定。这些已确定的变化将被仔细研究，以确定引起这些变化的分子机制，这些变化对基因产品生产的影响，以及这些变化对生物体适应性的整体影响。

The research project studies differences in the molecular structures of genes and genomes across a wide swath of organisms ranging from humans to parasites. In particular, the project seeks to answer the mystery of the origins of introns, intervening stretches of DNA that interrupt the genes of all eukaryotes, i.e., the organisms that have nucleated cells. By conducting the work at San Francisco State University, one of the most diverse comprehensive universities in the country, this work will support training in biological and computational sciences of individuals from underrepresented minority groups at early stages in their careers (undergraduate and masters students). The project seeks to answer the mystery of the origins of spliceosomal introns in eukaryotes. The vast majority of introns are DNA fragments inserted within protein-coding genes without a known function and with a quasi-random DNA sequence, raising the twin questions of (i) why are there introns; and (ii) how are introns created in evolution? To answer these questions, the project uses the strategy of identifying and studying recent cases of intron gain (creation of an intron) and loss (deletion of an intron from the genome). Recent gains and losses will be identified by direct genome-wide comparison between 50 groups of closely related organisms, as well as by comparison of individual intron sequences within the genomes of a larger set of 1000 organisms. These identified changes will be scrutinized to determine the molecular mechanisms that gave rise to these changes, the impact of these changes on production of gene products, and the overall impact of these changes on organismal fitness.