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Project Progress

Self-Reproducing (SL) Molecular Systems and Darwinian Chemistry (dm)

The primary goal of the Switzer laboratory is to synthesize Alternative Nucleic Acids (ANAs) to attempt the optimization of polymer structure subject to the constraints of prebiotic availability, template-directed reproduction, replication conservative mutation, and fitness. We have identified ANAs by taking small steps in “structure-space” away from RNA (the best model for a molecule bearing features both universal and unique to life) that may avoid some of the problems inherent in fulfillment of the aforementioned constraints. Specifically, the Switzer laboratory is examining ANAs with novel changes to (i) base-pairing domains, (ii) backbone charges and (iii) the sugar. These studies will help to define chemical parameters for molecular evolution. Moreover, our work addresses whether nucleic acid-like molecules are sufficient to enable the origin of life and what limitations exist for life elsewhere in the universe based on a single biopolymer (eg. RNA) rather than multiple biopolymers (DNA, RNA, proteins, carbohydrates). Accomplishments by our group for the past year include: (i) the discovery of surprising fidelity during non-enzymatic transcription of an unnatural base-pair, (ii) the discovery that DNA recombination is possible with artificial Watson-Crick base-pairs, (iii) an assessment of how tethered cations affect DNA topology, and (iv) the discovery that a DNA analogue bearing a simple acyclic sugar replacement of glycerol in place of ribose can support template-directed synthetic reactions.