The effects of genome size reduction on cellular processes

基因组大小减小对细胞过程的影响

• 批准号: 262988-2013
• 负责人: Fast, Naomi
• 金额: $ 3.64万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571312
• 关键词: effects; genome; size; reduction; cellular

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.

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翻译成蛋白质之前将内含子从信使 RNA 中去除，而这项任务是由称为剪接体的大型大分子细胞机器来执行的。然而，并非所有基因组都很大。随着基因组的减少，内含子等非编码序列可能会缩短或丢失，复杂的细胞机器的尺寸也会减小，组件也会减少。我建议研究具有已知最小核基因组的真核生物的剪接过程。识别不相关生物体中减少剪接系统的共同特征可以预测剪接体的功能核心，并识别系统中的其他限制（例如内含子序列特征），否则这些限制可能在更复杂的系统中被掩盖。 微孢子虫是单细胞真核寄生虫，拥有自然界最小的非细胞器基因组，是我的主要研究群体。虽然是动物常见的寄生虫，但仅对少数物种进行了基因组表征。为了增加我们对群体内基因组多样性的理解，并扩大我们对宿主-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（微小圆虫）的感染模式、基因组和转录本结构。 了解有机体多样性是理解这个星球上生命的关键，了解细胞水平的潜在多样性也同样重要。通过研究细胞系统中一个关键真核过程的灵活性，该过程高度减少但仍然发挥作用，我们可以获得机制上的理解。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。