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: RGPIN-2019-04203
• 负责人: Fast, Naomi
• 金额: $ 3.06万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=737479
• 关键词: effects; genome; size; reduction; cellular

Our own genomes are extremely large, possessing genes that include very long stretches of non-coding sequences called introns. For proper expression to occur, introns are removed, or spliced, from messenger RNAs by a large macromolecular, cellular machine: the spliceosome. However, not all genomes are large like those of humans. Eukaryotes possess a range of genome sizes, including genomes that are highly reduced. As genomes reduce in size, non-coding sequences (such as introns) can be shortened, or lost. Cellular machines are also affected, and undergo reduction by having fewer components and interaction partners. I propose to use a comparative approach to examine splicing in eukaryotes that have independently undergone reduction. Identifying common features of reduced splicing systems in diverse organisms allows prediction of core functional and mechanistic aspects of this process that are otherwise obscured by the myriad components in more complex systems. By strategically focusing on unicellular, free-living red algae and parasitic fungi, I propose to assess the effects of genome reduction on groups of microbial eukaryotes that are unrelated (sharing a very distant common ancestor), have reduced independently from one another, and possess different lifestyles/habitats. Therefore, identifying shared functional and mechanistic aspects of reduced splicing systems in these disparate groups will strengthen my prediction of their core importance, while also ensuring that observations are broadly relevant across eukaryotes. Just as we are challenged to understand the staggering level of organismal diversity on this planet, the underlying diversity of cellular biology is just as varied, fascinating, and complex. By examining a key eukaryotic process in a highly reduced cellular system, we gain insight into both the flexibility of the process, and its mechanistic underpinnings. This research is broadly impactful across diverse fields including cell biology, splicing biochemistry, molecular parasitology and phycology, and microbial genomics.

我们自己的基因组非常大，拥有的基因包括很长一段称为内含子的非编码序列。为了进行适当的表达，内含子被一个大分子的细胞机器——剪接体从信使rna上移除或剪接。然而，并不是所有的基因组都像人类一样大。真核生物具有一系列的基因组大小，包括高度缩小的基因组。随着基因组尺寸的减小，非编码序列（如内含子）可能缩短或丢失。细胞机器也受到影响，并且由于组件和交互伙伴的减少而减少。我建议使用比较的方法来检查在真核生物剪接，已经独立地经历了还原。识别不同生物中减少剪接系统的共同特征，可以预测这一过程的核心功能和机制方面，否则这些方面将被更复杂系统中的无数成分所掩盖。通过战略性地关注单细胞、自由生活的红藻和寄生真菌，我建议评估基因组减少对微生物真核生物群体的影响，这些群体不相关（共享一个非常遥远的共同祖先），彼此独立减少，拥有不同的生活方式/栖息地。因此，识别这些不同群体中减少剪接系统的共享功能和机制方面将加强我对其核心重要性的预测，同时也确保观察结果在真核生物中广泛相关。正如我们要理解这个星球上惊人的生物多样性所面临的挑战一样，细胞生物学的潜在多样性也同样多样、迷人和复杂。通过检查一个关键的真核过程在一个高度减少的细胞系统，我们深入了解这一过程的灵活性，以及它的机制基础。该研究在细胞生物学、剪接生物化学、分子寄生虫学和生理学以及微生物基因组学等多个领域具有广泛的影响。