Genetic studies of human evolution
Abstract/Contents
- Abstract
- Understanding what makes us human and how our species evolved, though enormous questions, present challenges worthy of study. With the advent and availability of genome sequencing for humans and non-human primates, and the technological advances in genetic manipulation and cell culture, we hold more tools than ever before with which to uncover the genetic and molecular basis of human evolution. In this thesis, I describe two complementary approaches to studying the genetic basis of human evolution. In the first, I describe our molecular and genetic studies of a human conserved deletion (hCONDEL584) that drives expression in the developing brain. We show that hCONDEL584 has enhancer activity localized to developing inhibitory interneurons that mimics the expression pattern of nearby gene Nxph1, develop and optimize techniques for further study of hCONDEL584 and Nxph1, recapitulate the human-specific deletion in mice and find differential expression of evolution- and disease-relevant genes in the adult brain, and propose a hypothesized mechanism of human-specific expansion of inhibitory interneurons through the human-specific deletion of enhancers of tumor suppressor genes in the developing brain. In the second approach, I introduce our new cell culture system for genetic mapping of traits divergent across humans and chimpanzees. This system utilizes human and chimpanzee pluripotent stem cells, and fuses them to create auto- and allo-tetraploid cells that we use to study gene expression and regulatory change across humans and chimpanzees. In demonstrating our new system for genetic mapping through panels of deletion lines and a recombinant, we uncover genes subject to species-specific trans-regulation, and propose a candidate species-specific trans-regulator that also has major roles in human neuro-developmental disease. Together, this work represents both forward and reverse genetic approaches to the study of human evolution, uncovers a number of evolutionary and disease-relevant genes and regulatory regions, and contributes to the field a novel system for the mapping of divergent traits across humans and chimpanzees.
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 | Grant, Rachel Lauren |
|---|---|
| Degree supervisor | Kingsley, David M. (David Mark) |
| Thesis advisor | Kingsley, David M. (David Mark) |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Luo, Liqun, 1966- |
| Degree committee member | Boettiger, Alistair |
| Degree committee member | Fuller, Margaret T, 1951- |
| Degree committee member | Luo, Liqun, 1966- |
| Associated with | Stanford University, Department of Developmental Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Rachel L. Grant. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/rr919hx9056 |
Access conditions
- Copyright
- © 2022 by Rachel Lauren Grant
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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