The effects of genome size reduction on cellular processes

我们自己的基因组非常大，拥有包括被称为内含子的非常长的非编码序列的基因。为了进行正确的表达，信使RNA中的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的基因组一样大。真核生物拥有一系列基因组大小，包括高度缩小的基因组。随着基因组大小的减少，非编码序列(如内含子)可能缩短或丢失。蜂窝机也会受到影响，由于组件和交互伙伴较少，蜂窝机的数量会减少。我建议使用一种比较的方法来研究真核生物中的剪接，这些剪接已经独立地经历了减少。识别不同生物体中简化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，否则这些方面会被更复杂系统中的无数组件所掩盖。通过战略性地将重点放在单细胞、自由生活的红藻和寄生真菌上，我建议评估基因组减少对不相关(共享非常遥远的共同祖先)、彼此独立减少、拥有不同生活方式/栖息地的微生物真核生物群体的影响。因此，在这些不同的类群中识别减少剪接系统的共同功能和机制方面将加强我对它们核心重要性的预测，同时也确保观察到的结果在真核生物中广泛相关。就像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种多样、引人入胜和复杂。通过研究高度简化的细胞系统中的一个关键的真核过程，我们获得了对该过程的灵活性及其机械基础的洞察。这项研究广泛影响不同的领域，包括细胞生物学、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。

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.