Developmental enhancers : ancient origins, neofunctionalization, and pleiotropy
Abstract/Contents
- Abstract
- In this work, I present two studies of the evolution and function of developmental enhancers. In the first study, I describe the discovery of the first examples of cis-regulatory elements that are conserved across the two great clades of the bilaterian tree (deuterostomes and protostomes). These bilaterian conserved regulatory elements (Bicores) are developmental enhancers that respond to key signaling pathways and have been conserved for approximately 650 million years. In vertebrates, Bicores have neofunctionalized to drive expression in the central nervous system. In the second study, I present a genome-wide set of putative enhancers that function in the development of the mammalian neocortex. These elements, identified through ChIP-seq, are validated through both computational and experimental approaches. I show that many elements are anciently conserved beyond mammals, and we show that older elements are more likely to be pleiotropic. Pleiotropic elements most likely function in other aspects of central nervous system development, and elements that are conserved to zebrafish function in the developing zebrafish forebrain. I also provide evidence that specific repeat families have played a major role in the generation of enhancers that function in neocortex development. Finally, in the conclusion, I discuss how enhancer neofunctionalization and pleiotropy fit into a model of enhancer evolution and the evo-devo framework.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Clarke, Shoa Long |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Bejerano, Gill, 1970- |
| Thesis advisor | Bejerano, Gill, 1970- |
| Thesis advisor | Bustamante, Carlos |
| Thesis advisor | Fuller, Margaret |
| Thesis advisor | Snyder, Michael, Ph. D |
| Advisor | Bustamante, Carlos |
| Advisor | Fuller, Margaret |
| Advisor | Snyder, Michael, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Shoa Long Clarke. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2013. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Lee Shoa Long Clarke
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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