All ETDs from UAB

Advisory Committee Chair

Eric J Sorscher

Advisory Committee Members

Stephen A Watts

Aubrey E Hill

Document Type

Thesis

Date of Award

2013

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Single Nucleotide Polymorphisms (SNPs) are traditionally seen as forming in a stochastic manner, with final distribution ascribed to processes such as purifying natural selection, genetic drift, shift, etc. The present study investigated contextual biases that underlie SNP patterns in 16 distinct murine strains, and tested relevance of these observations to human genomic DNA. We establish stereotypic nucleotide motifs that surround single base replacements in mammalian genes and propose a novel mechanism of SNP regulation. The findings contrast traditional notions in which SNPs occur `randomly' followed by purifying selection or are attributable to more `neutral' (unselected) formation. Instead, we propose that SNPs are often generated in a regulated fashion and at parallel locations. SNP-associated contexts also provide an explanation for patterns of eukaryotic codon usage as an adaptive strategy favoring exonic conservation. Our results indicate the need to reappraise classical assumptions of random SNP accrual that underlie features of evolution including models of species relatedness and divergence, ultra-conserved versus rapidly evolving segments of the mammalian genome, and rates of DNA evolution within coding as well as regulatory (non-coding) genomic compartments.

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