Chromatin activity identifies differential gene regulation across human ancestries
Abstract/Contents
- Abstract
- Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation. To address this, I co-devised an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, I find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, I show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding. Overall, this work indicates that some cis-regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This thesis provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pettie, Kade Ploussard |
|---|---|
| Degree supervisor | Fraser, Hunter B |
| Thesis advisor | Fraser, Hunter B |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Morrison, Ashby J |
| Degree committee member | Greenleaf, William James |
| Degree committee member | Morrison, Ashby J |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kade P. Pettie. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/ry407zk4957 |
Access conditions
- Copyright
- © 2022 by Kade Ploussard Pettie
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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