A sequence-based, population genetic model of regulatory pathway evolution

Troy Ruths, Rice University

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Complex phenotypes with genetic cause, such as inheritable traits or diseases, are understood through many processes, including regulatory pathways, but our evolutionary understanding of these critical regulatory pathway structures is undermined by poor models. Current models fail to preserve the underlying DNA-sequence structure of pathways and to incorporate population genetics; both are fundamental variables that vary over several orders of magnitude across the tree of life and have been shown to dramatically affect the results of evolution. In response, we build a pathway model of evolution from its underlying DNA structure and validate our model against a pertinent problem in genome evolution which has yet to be broached from a pathway perspective. Specifically, our model preserves DNA sequence characteristics through a novel data structure and pathway-level mutation and recombination rates that are functions of sequence properties. The utility of the model is validated with a study quantifying the advantages and disadvantages of expansive non-coding DNA regions on the establishment of optimal pathways. Because the model presented in this thesis rectifies many fundamental problems in previous models, it may serve as a critical tool for future work in pathway evolution.

Abstract Author(s): Troy Ruths and Luay Nakhleh