Physical Sciences and Mathematics Commons^™

7-Deazaguanines In Dna: Functional And Structural Elucidation Of A Dna Modification System, Samanthi Herath Gedara, Andrew Gustafson, Dirk Iwata-Reuyl, Multiple Additional Authors

Chemistry Faculty Publications and Presentations

The modified nucleosides 2′-deoxy-7-cyano- and 2′-deoxy-7-amido-7-deazaguanosine (dPreQ₀ and dADG, respectively) recently discovered in DNA are the products of the bacterial queuosine tRNA modification pathway and the dpd gene cluster, the latter of which encodes proteins that comprise the elaborate Dpd restriction–modification system present in diverse bacteria. Recent genetic studies implicated the dpdA, dpdB and dpdC genes as encoding proteins necessary for DNA modification, with dpdD–dpdK contributing to the restriction phenotype. Here we report the in vitro reconstitution of the Dpd modification machinery from Salmonella enterica serovar Montevideo, the elucidation of the roles of each protein and the X-ray …

Spontaneous Recombination Of Short Rnas To Increase Length And Complexity In Prebiotically Plausible Conditions, Benedict Arthur Smail

Dissertations and Theses

The RNA World hypothesis is an influential theory of how life arose on earth which posits that the earliest life forms carried out essential activities with RNA catalysts instead of proteins. Substantial evidence to support this theory comes from among others, the fact that the ribosome is a ribozyme, the existence of small RNA catalysts capable of high activity, and self-assembling ribozymes such as the Azoarcus ribozyme. Additional support has been provided by the directed evolution of various ribozymes and the reputed prebiotic synthesis of nucleotides and small RNA oligomers. However, it has long been challenging to show how long …

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 …

A Study Of Fragmentation And Spontaneous Covalent Self-Assembly Of The Azaorcus Ribozyme From Multiple Small Inactive Rna Fragments, Tharuka Sewwandi Jayathilaka

Dissertations and Theses

The question about the origins of life often appears as a difficult question to answer. A more reliable candidate molecule for the chemical origins of life would be a molecule that is capable of making copies of itself from simple precursors. With the finding of the catalytic activities of RNA molecules by Thomas Cech and Sid Altman in late 1980s, the term ribozyme was introduced to define an RNA molecule with catalytic activity. The RNA World is a conceptual period in the early stages in the development of life because RNA simultaneously possesses evolvability and catalytic function. An RNA molecule …

The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates

Dissertations and Theses

How life originated from physical and chemical processes is one of the great questions still unanswered today. Studies towards this effort have transitioned from the notion of a single self-replicating entity to the idea that a network of interacting molecules made this initial biological leap. In order to understand the chemical kinetic and thermodynamic mechanisms that could engender pre-life type networks we present an empirical characterization of a network of RNA recombinase molecules. We begin with 1-, 2-, and 3-molecular ensembles and provide a game theoretic analysis to describe the frequency dependent dynamics of competing and cooperating RNA genotypes. This …

Interpretation Of Chemical Environments By Rna And The Implications To The Origins Of Life, Brian Larson

Dissertations and Theses

We describe the initial realization of behavior in the biosphere, which we term behavioral chemistry. If molecules are complex enough to attain a stochastic element to their structural conformation in such a way as to radically affect their function in a biological (evolvable) setting, then they have the capacity to behave. This circumstance is described here as behavioral chemistry, unique in its definition from the colloquial chemical behavior. This transition between chemical behavior and behavioral chemistry need be explicit when discussing the root cause of behavior, which itself lies squarely at the origins of life and is the foundation 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 …