2003 Annual Science Report
Scripps Research Institute Reporting | JUL 2002 – JUN 2003
Switzer - Self-Reproducing Molecular Systems and Darwinian Chemistry
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 and (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 (deoxyribonucleic acid (DNA), RNA, proteins, carbohydrates). Accomplishments by our group for the past year include:
(i) discovery of a novel metallo-base-pair with increased thermal stability over all natural base-pairs,
(ii) the discovery that non-standard, 2’,5’-linked DNA is a template for enzymatic synthesis of natural DNA with a variety of DNA polymerases and reverse transcriptases, directing the incorporation of all four natural nucleotides with fidelity. This finding demonstrates that, surprisingly, DNA replication does not require double helix formation as 2’,5’-linked DNA is known not to associate with 3’,5’-linked-DNA. In the present case, it appears that the enzyme can serve as a “template for the template” and make up for structural and functional deficiencies.
(iii) the design and initial evaluation of a new peptide nucleic acid that transcends previous known shortcomings of this molecular chimera of nucleic acids and peptides, opening the way to the creation of long polymer chains and highly functional proto-biopolymers that could serve as transitional polymers on the way to the present DNA/RNA/protein world.
PROJECT INVESTIGATORS:Christopher Switzer
PROJECT MEMBERS:Surajit Sinha
RELATED OBJECTIVES:Objective 3.2
Origins and evolution of functional biomolecules