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The analysis and prediction of DNA structure

As genome sequencing projects begin to come to completion, the
challenge becomes one of determining how to understand the information
contained within the DNA. DNA is a polymorphic macromolecule; the A- B-
and Z-DNA conformations have been observed by a variety of physical
techniques. The magnitude of the energetic differences between these
conformations suggests that these conformations may be important
biologically and thus relevant in the analysis of genomes. A computer
program, NASTE, was developed to evaluate the helical parameters of the
set of Z-DNA crystal structures in order to determine the true conformation
of Z-DNA and to understand the effects of various factors on the observed
structure and stability. A thermodynamic method, elucidated in part with a
genetic algorithm, was developed to predict the sequence-dependent
propensity of DNA sequences for A- versus B-DNA in both the crystal and
in natural DNA. Predictions from this method were tested by studying the
conformation of short oligonucleotides using circular dichroism
spectroscopy. Finally, the thermodynamic method was applied in an
algorithm, AHUNT, to identify regions in genomic DNA with a high
propensity to form A-DNA. Significant amounts of A-DNA were identified
in eukaryotic and archeabacterial genes. E. coli genes have less A-DNA
than would be predicted from their (G+C) content. These results are
discussed with respect to the intracellular environment of the genomes. / Graduation date: 1998
Date11 March 1998
CreatorsBasham, Beth E.
ContributorsHo, P. Shing
Source SetsOregon State University
Detected LanguageEnglish

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