<p>The central dogma of molecular biology relies on the correct Watson-Crick (WC) geometry of canonical deoxyribonucleic acid (DNA) dG•dC and dA•dT base pairs to replicate and transcribe genetic information with speed and an astonishing level of fidelity. In addition, the Watson-Crick geometry of canonical ribonucleic acid (RNA) rG•rC and rA•rU base pairs is highly conserved to ensure that proteins are translated with high fidelity. However, numerous other potential nucleobase tautomeric and ionic configurations are possible that can give rise to entirely new pairing modes between the nucleotide bases. Very early on, James Watson and Francis Crick recognized their importance and in 1953 postulated that if bases adopted one of their less energetically disfavored tautomeric forms (and later ionic forms) during replication it could lead to the formation of a mismatch with a Watson-Crick-like geometry and could give rise to “natural mutations.” </p><p>Since this time numerous studies have provided evidence in support of this hypothesis and have expanded upon it; computational studies have addressed the energetic feasibilities of different nucleobases’ tautomeric and ionic forms in siico; crystallographic studies have trapped different mismatches with WC-like geometries in polymerase or ribosome active sites. However, no direct evidence has been given for (i) the direct existence of these WC-like mismatches in canonical DNA duplex, RNA duplexes, or non-coding RNAs; (ii) which, if any, tautomeric or ionic form stabilizes the WC-like geometry. This thesis utilizes nuclear magnetic resonance (NMR) spectroscopy and rotating frame relaxation dispersion (R1ρ RD) in combination with density functional theory (DFT), biochemical assays, and targeted chemical perturbations to show that (i) dG•dT mismatches in DNA duplexes, as well as rG•rU mismatches RNA duplexes and non-coding RNAs, transiently adopt a WC-like geometry that is stabilized by (ii) an interconnected network of rapidly interconverting rare tautomers and anionic bases. These results support Watson and Crick’s tautomer hypothesis, but additionally support subsequent hypotheses invoking anionic mismatches and ultimately tie them together. This dissertation shows that a common mismatch can adopt a Watson-Crick-like geometry globally, in both DNA and RNA, and whose geometry is stabilized by a kinetically linked network of rare tautomeric and anionic bases. The studies herein also provide compelling evidence for their involvement in spontaneous replication and translation errors.</p> / Dissertation

The set of all sequences that are generated by a bio-molecular protocol forms a language over the four letter alphabet Delta = [A,G,C,T]. This alphabet is associated with natural involution mapping Theta, A maps to T and G maps to C which is an antimorphism of Delta* In order to avoid undesirable Watson-Crick bonds between the words the language has to satisfy certain coding properties. Hence for an involution Theta we consider involution codes: Theta-infix, Theta-comma-free, Theta-k-codes and Theta-subword-k-codes which avoid certain undesirable hybridization. We investigate the closure properties of these codes and also the conditions under which both X and X+ are the same type of involution codes. We provide properties of the splicing system such that the language generated by the system preserves the desired properties of code words. Algebraic characterizations of these involutions through their syntactic monoids have also been discussed. Methods of constructing involution codes that are strictly locally testable are also given. General methods for generating such involution codes are given and teh information capacity of these codes show to be optimal in most cases. A specific set of these codes were chosen for experimental testing and the results of these experiments are presented.

Watson and Crick’s double-helical model of DNA is considered to be one of the great discoveries in biology. However, in 1976, two groups of scientists, one in New Zealand, the other in India, independently published essentially the same radical alternative to the double helix. The alternative, Side-By-Side (SBS) or ‘warped zipper’ conformation for DNA is not helical. Rather than intertwine, as do Watson and Crick’s helices, its two exoskeletal strands are topologically independent. Thus, unlike the double helix, they may separated during replication without unwinding. This dissertation presents, but does not arbitrate among scientific arguments. Its concerns are meta-scientific; in particular, why and how the individuals who invented the & ‘warped zipper’ came to do so. Against Popper and most recent philosophers of science, it is taken to be “the business of epistemology to produce what has been called a ‘rational reconstruction’ of the steps that have led the scientist to a discovery [Popper (1972), p.31, emphasis in the original].” On the received view, the invention of the ‘warped zipper’ must be irrational or, at best, non-rational thereby excluding from philosophical investigation. I establish that this philosophical dogma is not true a priori, as is usually supposed, and, in the case of the SBS structure of DNA, false a posteriori. The motivation for, and development of the SBS structure for DNA reveals a process best characterized as significantly, though not entirely, rational.

Watson and Crick’s double-helical model of DNA is considered to be one of the great discoveries in biology. However, in 1976, two groups of scientists, one in New Zealand, the other in India, independently published essentially the same radical alternative to the double helix. The alternative, Side-By-Side (SBS) or ‘warped zipper’ conformation for DNA is not helical. Rather than intertwine, as do Watson and Crick’s helices, its two exoskeletal strands are topologically independent. Thus, unlike the double helix, they may separated during replication without unwinding. This dissertation presents, but does not arbitrate among scientific arguments. Its concerns are meta-scientific; in particular, why and how the individuals who invented the & ‘warped zipper’ came to do so. Against Popper and most recent philosophers of science, it is taken to be “the business of epistemology to produce what has been called a ‘rational reconstruction’ of the steps that have led the scientist to a discovery [Popper (1972), p.31, emphasis in the original].” On the received view, the invention of the ‘warped zipper’ must be irrational or, at best, non-rational thereby excluding from philosophical investigation. I establish that this philosophical dogma is not true a priori, as is usually supposed, and, in the case of the SBS structure of DNA, false a posteriori. The motivation for, and development of the SBS structure for DNA reveals a process best characterized as significantly, though not entirely, rational.

Lindenmayer (L) systems form a class of interesting computational formalisms due to their parallel nature, the various circumstances under which they operate, the restrictions imposed on language acceptance, and other attributes. These systems have been extensively studied in the Formal Languages literature. In the past decade a new type of Lindenmayer system had been proposed: Watson-Crick Lindenmayer Systems. These systems are essentially a marriage between Developmental systems and DNA Computing. At their heart they are Lindenmayer systems augmented with a complementary relation amongst elements in the system just as the base pairs of DNA strands can be complementary with respect to one another. When conditions and a mechanism for 'switching' the state of a computation to it's complementary version are provided then these systems can become surprisingly more powerful than the L systems which form their backbone. This dissertation explores the computational power of new variants of Watson-Crick L systems. It is found that many of these systems are Computationally-Complete. These investigations differ from prior ones in that the systems under consideration have extended alphabets and usually Regular Triggers for complementation are considered as opposed to Context-Free Triggers investigated in previous works. / Thesis (Master, Computing) -- Queen's University, 2010-12-06 18:29:23.584

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