The effects of genome size reduction on cellular processes

人类基因组非常大，我们的基因包含很长的非编码序列，称为内含子。正确的基因表达需要在将信使RNA翻译成蛋白质之前将内含子从信使RNA中移除，而这项任务是由一种称为剪接体的大分子细胞机器执行的。然而，并不是所有的基因组都很大。随着基因组的减少，非编码序列（如内含子）可能会缩短或丢失，复杂的细胞机器的大小也会减少，组件也会减少。我打算用已知最小的核基因组来研究真核生物中的剪接过程。确定减少剪接系统在不相关的生物体的共同特点，可以预测的剪接体的功能核心，并确定系统中的其他限制（如内含子序列特征），否则可能会被掩盖在更复杂的systems.Microsporidia是单细胞，真核寄生虫，拥有自然界最小的非细胞器基因组，是我的主要研究小组。虽然常见的动物寄生虫，基因组的特点，只有少数物种。为了增加我们对组内基因组多样性的理解，并拓宽我们对宿主-寄生虫关系的理解，我建议描述一种新的线虫微孢子虫寄生虫的感染模式、基因组和转录本结构（微观圆形蠕虫）。理解生物多样性是理解这个星球上生命的关键，理解细胞水平上潜在的多样性也同样重要。通过研究细胞系统中一个关键的真核过程的灵活性，这个过程高度减少，但仍然起作用，我们可以获得机械的理解。这项研究影响了进化遗传学、分子寄生虫学、剪接生物化学和微生物基因组学领域。

The human genome is very large, and our genes contain very long stretches of non-coding sequences called introns. Proper gene expression requires that introns be removed from messenger RNAs prior to their translation into proteins, and this task is carried out by a large, macromolecular, cellular machine called the spliceosome. However, not all genomes are large. As genomes are reduced, non-coding sequences such as introns can be shortened, or lost, and complex cellular machines are reduced in size and have fewer components. I propose to examine the process of splicing in eukaryotes with the smallest nuclear genomes known. Identifying common features of reduced splicing systems in unrelated organisms allows for predicting a functional core of the spliceosome, and identifies other constraints in the system (such as intron sequence features) that might otherwise be obscured in more complex systems.Microsporidia are unicellular, eukaryotic parasites that possess Nature's smallest non-organelle genomes and are my main study group. Although common parasites of animals, genomes are characterized for only a small number of species. In an attempt to increase our understanding of genome diversity within the group, and broaden our understanding of host-parasite relationships, I propose to characterize the infection pattern, and genome and transcript architecture of a new microsporidian parasite of nematodes (microscopic round worms).Understanding organismal diversity is key to comprehending life on this planet, and understanding the underlying diversity at the cellular level is just as crucial. By investigating the flexibility of a key eukaryotic process in a cellular system that is highly reduced, yet still functions, we can gain mechanistic understanding. This research impacts the fields of evolutionary genetics, molecular parasitology, splicing biochemistry and microbial genomics.