First Advisor

Niles Lehman

Term of Graduation

Summer 2008

Date of Publication


Document Type


Degree Name

Doctor of Philosophy (Ph.D.) in Chemistry






RNA, Catalytic RNA, Autocatalysis, Life -- Origin



Physical Description

1 online resource (2, vii, 101 pages)


This research demonstrates chemical reactions of RNA molecules that allow them to increase in length, from non-catalytic oligomers to complex RNA enzymes. The purpose of this research was to explain the origin of large RNA polymers required for life to begin in the proposed "RNA World". To do this, the Azoarcus group I ribozyme was engineered to catalyze phosphodiester exchange reactions that result in the recombination of short oligomer substrates marked by 5'CAU3' recognition tags.

To demonstrate the ability to produce catalytic RNA sequences through recombination, substrate oligomers were synthesized that could produce ribozymes if large portions of each sequence were recombined into a single molecule. The results demonstrated: (i) complex structures, such as the class I ligase ribozyme, can be constructed through the recombination of shorter substrates by the Azoarcus ribozyme, (ii) that the Azoarcus ribozyme itself can be constructed through recombination of shorter substrates, (iii) the "substrates" alone can catalyze the production of the Azoarcus ribozyme by forming non-covalent ribozyme complexes, (iv) the construction of the Azoarcus ribozyme from shorter substrates leads to autocatalysis, and (v) low level mutants of the Azoarcus ribozyme are the most likely to be assembled into covalent ribozymes when starting from a pool of mutated "substrates". These results demonstrate that large RNA molecules can arise from shorter oligomers through recombination. Moreover, complex phenotypes can spontaneously emerge from groups of RNA molecules giving rise to selection at the chemical level.


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