Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2025054118.
Functional biomolecules, such as RNA, encapsulated inside a protocellular membrane are believed to have comprised a very early, critical stage in the evolution of life, since membrane vesicles allow selective permeability and create a unit of selection enabling cooperative phenotypes. The biophysical environment inside a protocell would differ fundamentally from bulk solution due to the microscopic confinement. However, the effect of the encapsulated environment on ribozyme evolution has not been previously studied experimentally. Here, we examine the effect of encapsulation inside model protocells on the self-aminoacylation activity of tens of thousands of RNA sequences using a high-throughput sequencing assay. We find that encapsulation of these ribozymes generally increases their activity, giving encapsulated sequences an advantage over nonencapsulated sequences in an amphiphile-rich environment. In addition, highly active ribozymes benefit disproportionately more from encapsulation. The asymmetry in fitness gain broadens the distribution of fitness in the system. Consistent with Fisher's fundamental theorem of natural selection, encapsulation therefore leads to faster adaptation when the RNAs are encapsulated inside a protocell during in vitro selection. Thus, protocells would not only provide a compartmentalization function but also promote activity and evolutionary adaptation during the origin of life.
功能生物分子,如 RNA,被包裹在原细胞的膜内,被认为是生命进化的一个非常早期的关键阶段,因为膜囊允许选择性渗透,并创造一个选择单位,使合作表型成为可能。由于微观限制,原细胞内的生物物理环境将与本体溶液有根本的不同。然而,以前的实验并没有研究过囊封环境对核酶进化的影响。在这里,我们使用高通量测序分析,研究了在模型原细胞内包封对数千个 RNA 序列自我氨酰化活性的影响。我们发现,这些核酶的包封通常会增加它们的活性,使囊封序列在富含两亲物的环境中比非囊封序列具有优势。此外,高度活跃的核酶从封装中获得的优势不成比例地更大。适应度增益的不对称性拓宽了系统中适应度的分布。与费希尔自然选择的基本定理一致,因此,当 RNA 在体外选择过程中原细胞内被包裹时,封装会导致更快的适应。因此,原细胞不仅提供了一个隔室化的功能,而且在生命起源过程中促进了活性和进化适应。