Evaluating the Fitness of a Pre-RNA World Polymer by Darwinian Evolution

通过这一奖项，生命过程化学计划资助亚利桑那州立大学的约翰·查普特教授评估苏糖核酸(TNA)作为功能性遗传聚合物的适合性。该项目将把化学合成与分子生物学和遗传学相结合，以分离模仿生命的一种关键紧急性质的TNA分子--将遗传信息从一条链复制到另一条链的能力。我们的目标是进化出能够将自己折叠成定义明确的三维结构的TNA分子，这些结构带有催化域，可以模板指导两条TNA链的连接。这一过程被称为连接，将证明早期的遗传聚合物可以执行复制遗传信息所需的化学作用。适合性将通过比较TNA连接酶与以前发现的DNA和RNA连接酶的催化效率来确定。这项研究的信息将提供新的洞察力，以了解支撑在“非天然”苏糖骨架上的核酸的基本化学，这与基本的生物功能有关。人们普遍认为，地球上的生命是通过一系列离散的化学步骤产生的，这些步骤产生了具有DNA基因组和蛋白质酶的生物体。从化学到生物的道路可能由许多单独的步骤组成，每一步都提出了自己的一系列科学问题。最有趣的问题之一涉及DNA的起源以及替代遗传聚合物在我们遗传系统的进化中可能扮演的角色。根据一种假设，生命是从能够存储信息和催化反应的自我复制的遗传聚合物进化而来的。据推测，任何这样的分子都需要存储遗传信息，并将这些信息传递给后代分子。在这个项目中，我们将通过检查一种基于4-碳糖骨架的用于传递遗传信息的替代潜在支架，并通过询问这种核酸是否可以复制其自身序列的部分来达到可能的极限。此外，该项目还包括一个重要的推广部分，旨在增加传统上在STEM学科中代表性不足的群体的参与。该奖项由生物科学(BIO)理事会分子和细胞生物科学(MCB)司系统和合成生物学专题组共同资助。

With this award, the Chemistry of Life Processes Program is funding Professor John Chaput of Arizona State University to evaluate the fitness of threose nucleic acid (TNA) as a functional genetic polymer. This project will combine chemical synthesis with molecular biology and genetics to isolate TNA molecules that emulate a key emergent property of life-the ability to copy genetic information from one strand to another. The goal is to evolve TNA molecules that can fold themselves into well-defined three-dimensional structures with catalytic domains that can template-direct the joining of two TNA strands. This process, referred to as ligation, would demonstrate that early genetic polymers could have performed the chemistry necessary to copy genetic information. Fitness will be determined by comparing the catalytic efficiency of TNA ligases to previously discovered DNA and RNA ligases. Information from this study will provide new insight into the fundamental chemistry of nucleic acids supported on an "unnatural" threose sugar backbone, as relates to essential biological function. It is widely believed that life on Earth arose through a series of discrete chemical steps that gave rise to organisms with DNA genomes and protein enzymes. The path from chemistry to biology likely consisted of many individual steps, each raising its own set of scientific questions. One of the most interesting questions concerns the origin of DNA and the role that alternative genetic polymers may have played in the evolution of our genetic system. According to one hypothesis, life evolved from self-replicating genetic polymers that could store information and catalyze reactions. Presumably, any such molecule would have needed to store genetic information and pass that information along to progeny molecules. In this project, we will push the limits of the possible by examining an alternative potential scaffold for transmitting genetic information, based upon a 4-carbon sugar backbone, and by asking whether such a nucleic acid can copy portions of its own sequence. In addition, this project includes an important outreach component designed to increase participation of members of groups that are traditionally underrepresented in the STEM disciplines.This award is co-funded by the Systems and Synthetic Biology Cluster in the Molecular and Cellular Biosciences (MCB) Division of the Biological Sciences (BIO) Directorate.