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Dissecting the anatomy of regulatory divergence

$672,999FY2014BIONSF

University Of Chicago, Chicago IL

Investigators

Abstract

Abstract Ilya Ruvinsky Proposal #: 1355093 Title: Dissecting the anatomy of regulatory divergence? Gene expression patterns change as species evolve, and it is clear that some changes in gene expression are visible as changes in genetically-encoded traits. Less well-understood is the observation that visibly conserved traits in different species are sometimes specified by divergent gene regulatory mechanisms. The goal of the work proposed here is to understand how changes in gene expression influence traits in different species. Results from this study will not only impact our understanding of the evolution of developmental mechanisms, but also our understanding of the discovery of broader evolutionary trends. Dr. Ruvinsky will incorporate findings of this work into his teaching of undergraduate and graduate students at the University of Chicago as well as to science teachers of Chicago Public Schools. Research in Dr. Ruvinsky?s laboratory will involve undergraduate and graduate students who will be trained in experimental and computational approaches central to this proposal. The PI and other members of the laboratory will present their findings at a variety of scientific meetings. The Ruvinsky Laboratory at the University of Chicago has established the gene unc-47 in Caenorhabditis nematodes as a model system for the study of gene regulatory evolution. Despite an apparently conserved expression pattern among these nematode species, the mechanisms that control unc-47 have diverged. The PI proposes three aims. First, Dr. Ruvinsky will dissect in detail the divergence of cis-regulation of the unc-47 gene in Caenorhabditis. Combining comparative and functional approaches, this work will provide a detailed picture of changes, possibly at the single-nucleotide resolution, that led to the divergence of regulatory mechanisms, while preserving the expression pattern. Second, using both standard and state-of-the-art molecular genetic methods, Dr. Ruvinsky will identify compensatory mutations in trans(cription) factors that permitted cis-regulatory divergence of unc-47 without changes to the expression pattern of the gene. Finally, Dr. Ruvinsky will determine the generality of the principles of regulatory divergence inferred from the unc-47 locus. Several genes have been identified that retain conserved expression in different species, while being regulated in subtly different ways. The goal of this aim is to test whether the rules governing changes in unc-47 regulation apply to other genes. Together these experiments promise to provide a highly detailed mechanistic view of gene regulatory evolution and thus contribute to the study of Evo-Devo.

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