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.
