The Biodesign Institute at Arizona State University
Life presumably arose through a series of discrete steps in which chemical systems gave rise to unicellular organisms with DNA genomes and protein enzymes. As we study the path from chemistry to biology, several interesting scientific questions arise that are worthy of experimental investigation. One question that has captured our attention concerns the origin of our genetic material. According to the RNA world hypothesis, early life forms were composed of RNA molecules that stored genetic information and catalyzed chemical reactions. Although the chemical plausibility of the RNA world remains strong, problems associated with the stability and replication of RNA have led some to postulate that RNA was preceded in evolutionary history by a simpler genetic material. One could imagine that whatever chemistry gave rise to RNA would have produced other types of RNA analogues, some of which could have preceded or even competed directly with RNA. In this hypothetical pre-RNA world, threose nucleic acid (TNA)—an artificial genetic polymer in which the natural ribose sugar found in RNA has been replaced with an unnatural threose sugar—has received considerable attention due to the chemical simplicity of threose relative to ribose and the ability for TNA to exchange genetic information with RNA. Although TNA-RNA pairing provides a plausible mechanism for the transfer of information between successive genetic systems, viable RNA progenitor candidates would have also needed to fold themselves into shapes that could perform functions, like ligand binding and catalysis. To explore the fitness of TNA as a primordial genetic polymer, we have developed a Darwinian evolution system that makes it possible to evolve functional TNA molecules in response to external stimuli. In this talk, I will discuss our progress in the coding and decoding of sequence-defined TNA polymers and preliminary evidence supporting the role of TNA as an RNA progenitor.