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Interactions Between The Azoarcus Ribozyme And Manganese (Ii) Divalent Cations, Joshua Martwick

University Honors Theses

The RNA world hypothesis suggests that RNA systems were the first form of life on the planet, beginning to appear approximately 4 billion years ago. Group I introns are self-splicing RNA elements in extant organisms and use Mg²⁺ as the principle divalent cation to promote catalysis. The group I intron ribozyme from Azoarcus is frequently used in origin of life studies, partially due to its autocatalytic abilities - the Azoarcus ribozyme is able to be broken into fragments and reassemble itself into its fully functional ribozyme. Previous work identified metal binding sites on the Azoarcus ribozyme which use both …

Spontaneous Advent Of Genetic Diversity In Rna Populations Through Multiple Recombination Mechanisms, Benedict A. Smail, Bryce E. Clifton, Ryo Mizuuchi, Niles Lehman

Chemistry Faculty Publications and Presentations

There are several plausible abiotic synthetic routes from prebiotic chemical materials to ribonucleotides and even short RNA oligomers. However, for refinement of the RNA World hypothesis to help explain the origins of life on the Earth, there needs to be a manner by which such oligomers can increase their length and expand their sequence diversity. Oligomers longer than at least 10-20 nucleotides would be needed for raw material for subsequent natural selection. Here, we explore spontaneous RNA-RNA recombination as a facile means by which such length and diversity enhancement could have been realized. Motivated by the discovery that RNA oligomers …

Topological And Thermodynamic Factors That Influence The Evolution Of Small Networks Of Catalytic Rna Species, Jessica Anne Mellor Yeates, Philippe Nghe, Niles Lehman

Chemistry Faculty Publications and Presentations

An RNA-directed recombination reaction can result in a network of interacting RNA species. It is now becoming increasingly apparent that such networks could have been an important feature of the RNA world during the nascent evolution of life on the Earth. However, the means by which such small RNA networks assimilate other available genotypes in the environment to grow and evolve into the more complex networks that are thought to have existed in the prebiotic milieu are not known. Here, we used the ability of fragments of the Azoarcus group I intron ribozyme to covalently self-assemble via genotype-selfish and genotype-cooperative …

Empirical Demonstration Of Environmental Sensing In Catalytic Rna: Evolution Of Interpretive Behavior At The Origins Of Life, Niles Lehman, Tess Bernhard, Brian C. Larson, Andrew J.N. Robinson, Christopher C.B. Southgate

Chemistry Faculty Publications and Presentations

Background: The origins of life on the Earth required chemical entities to interact with their environments in ways that could respond to natural selection. The concept of interpretation, where biotic entities use signs in their environment as proxy for the existence of other items of selective value in their environment, has been proposed on theoretical grounds to be relevant to the origins and early evolution of life. However this concept has not been demonstrated empirically.

Results: Here, we present data that certain catalytic RNA sequences have properties that would enable interpretation of divalent cation levels in their environment. …

Serial Transfer Can Aid The Evolution Of Autocatalytic Sets, Wim Hordijk, Nilesh Vaidya, Niles Lehman

Chemistry Faculty Publications and Presentations

Background: The concept of an autocatalytic set of molecules has been posited theoretically and demonstrated empirically with catalytic RNA molecules. For this concept to have significance in a realistic origins-of-life scenario, it will be important to demonstrate the evolvability of such sets. Here, we employ a Gillespie algorithm to improve and expand on previous simulations of an empirical system of self-assembling RNA fragments that has the ability to spontaneously form autocatalytic networks. We specifically examine the role of serial transfer as a plausible means to allow time-dependent changes in set composition, and compare the results to equilibrium, or "batch" scenarios. …

Spontaneous Cooperative Assembly Of Replicative Catalytic Rna Systems, Nilesh Vaidya

Dissertations and Theses

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 …

One Rna Plays Three Roles To Provide Catalytic Activity To A Group I Intron Lacking An Endogenous Internal Guide Sequence, Nilesh Vaidya, Niles Lehman

Chemistry Faculty Publications and Presentations

Catalytic RNA molecules possess simultaneously a genotype and a phenotype. However, a single RNA genotype has the potential to adopt two or perhaps more distinct phenotypes as a result of differential folding and/or catalytic activity. Such multifunctionality would be particularly significant if the phenotypes were functionally inter-related in a common biochemical pathway. Here, this phenomenon is demonstrated by the ability of the Azoarcus group I ribozyme to function when its canonical internal guide sequence (GUG) has been removed from the 5? end of the molecule, and added back exogenously in trans. The presence of GUG triplets in noncovalent fragments of …

The Original Build Up Of Genetic Information By Rna Recombination, Eric John Hayden

Dissertations and Theses

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'CAU^3' 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 …