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Project Progress

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 ribonucleic acid (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) 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) discovery of a non-standard base-pair that provides a vast improvement in the efficiency of non-enzymatic template directed synthesis over the canonical A•T base-pair, (ii) an assessment of how tethered cations affect DNA topology, (iii) discovery of new methodology for the selection of DNA aptamers that incorporate alternative nucleic acids, (iv) a full comparison of the thermodynamic behavior of the non-standard iso-guanine•iso-cytosine base pair and its sulfur counterpart, the 2-thio-isoguanine•iso-cytosine pair. Several of these findings are discussed below in more detail.