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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746331
• 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，拥有包括非常长的非编码序列（称为内含子）的基因。为了正确表达，内含子被一个大的大分子细胞机器（剪接体）从信使RNA中移除或剪接。然而，并不是所有的基因组都像人类一样大。真核生物拥有一系列的基因组大小，包括高度减少的基因组。随着基因组的缩小，非编码序列（如内含子）可能会缩短或丢失。细胞机器也受到影响，并通过减少组件和交互伙伴而减少。我建议使用比较的方法来检查剪接在真核生物已经独立经历了减少。识别不同生物体中减少剪接系统的共同特征允许预测该过程的核心功能和机制方面，否则这些方面会被更复杂系统中的无数组件所掩盖。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不相关的微生物真核生物群体的影响（共享一个非常遥远的共同祖先），彼此独立减少，并拥有不同的生活方式/栖息地。因此，在这些不同的群体中确定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。正如我们面临着理解这个星球上生物多样性惊人水平的挑战一样，细胞生物学的潜在多样性也同样多样，迷人，复杂。通过检查一个关键的真核细胞过程中的高度简化的细胞系统，我们深入了解这一过程的灵活性，及其机制的基础。这项研究在包括细胞生物学、剪接生物化学、分子寄生虫学和藻类学以及微生物基因组学在内的各个领域都具有广泛的影响力。