First Advisor

Niles Lehman

Date of Publication

Fall 1-1-2012

Document Type


Degree Name

Doctor of Philosophy (Ph.D.) in Chemistry






Catalytic RNA, RNA -- Research, Life -- Origin



Physical Description

1 online resource (ix, 126 p.) : ill. (some col.)


The RNA World hypothesis proposes a period of time during the origins of life in which RNA molecules were the only source of both genotypes and phenotypes. Although a vast amount of evidence has been obtained in support of this hypothesis, a few critical demonstrations are lacking. A most crucial one is a demonstration of self-replication of RNA molecule from prebiotic soup. Previously in the Lehman laboratory, it has been demonstrated that a 198-nucleotide molecule derived from the Azoarcus group I intron can self-assemble from up to four fragments of RNA via recombination. Furthermore, the covalent full-length molecules are catalytically active and can make copies of themselves from the remaining pieces in the solution leading to their autocatalytic growth. I was able to demonstrate how this recombination system can overcome different obstacles and evolve to be an efficient replicating system. I discovered the ability of a single RNA fragment to be multifunctional in a single reaction pathway during RNA recombination events that avoids the necessity of multiple genotypes. I also confirmed the capacity of self-replicating ribozymes to form cooperative catalytic cycles and networks that would potentially prevent informational decay. Finally, I have discovered a recycling phenomenon in the RNA recombination system that exploits dynamic covalent chemistry. Recycling provides the earliest replicating system with adequate concentrations of reagents and ability to explore sequence space. Together these findings have improved our understanding of RNA recombination and bolstered the plausibility of the RNA World.


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