Computational approaches towards the integration of functional and comparative datasets in the evolution of gene regulation /

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Bibliographic Details
Author / Creator:Arthur, Robert K., author.
Ann Arbor : ProQuest Dissertations & Theses, 2015
Description:1 electronic resource (111 pages)
Format: E-Resource Dissertations
Local Note:School code: 0330
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Other authors / contributors:University of Chicago. degree granting institution.
Notes:Advisors: Kevin P. White Committee members: Martin Kreitman; Manyuan Long; Ilya Ruvinsky; Joseph Thornton.
Dissertation Abstracts International, Volume: 77-05(E), Section: B.
Summary:The evolution of gene regulatory sequences is a complex subject, fraught with difficulties. In the following dissertation, I apply novel, functional datasets to better understand questions within the field of regulatory evolution. By computationally integrating data from these emerging techniques, I argue that we can better understand how selection operates on regulatory genes and elements. In Chapter 1, I introduce the outline of the subject matter, and sketch an argument for bringing genomic datasets to bear. In Chapter 2, I probe the relationship between function and evolutionary rate, using a meta-analysis of existing datasets which had tested the extent to which single-nucleotide substitutions could change gene expression. In Chapter 3, I examine function and conservation through the lens of the architecture of cis-regulatory elements. By combining ChIP-seq and DNase-seq datasets, I show that we can interrogate the arrangement of bound sites within elements, and that this information bears on the probability that such elements will be found in different species. In Chapter 4, I turn to another layer of the regulatory apparatus, the histone modification H3K27me3. I show that the evolution of this modification is coupled to gene duplication in a variety of interesting ways. One gene which shows an especially rapid pattern of H3K27me3 evolution is Zeus, whose protein-coding evolution I study further in Chapter 5. In collaboration with Ben Krinsky, we find evidence for a cis-trans coevolutionary process, driven by the emergence of Zeus. Finally, I conclude in Chapter 6 with an overview of the research, some emerging lessons from it, and future frontiers which remain to be addressed.