Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing
Abstract/Contents
- Abstract
- Epistasis represents the deviation from the expected outcome of mutations due to genetic interactions between two or more loci. Decades of research have reported on its effects in molecular biology across the tree of life, and its pervasiveness in the genetic architecture of complex traits. However, knowledge of how molecular epistasis shapes natural populations and the evolution of species is limited, and the factors associated with the incidence of genetic interactions remain poorly understood. In this dissertation, I present results from a high-throughput screen of natural variants conducted in four genetically diverse yeast strains that systematically quantifies epistasis caused by genetic background effects at single nucleotide resolution. Almost a quarter of natural variants affecting fitness in a common laboratory environment show a dependence on strain background, where advantageous effects in one strain are instead neutral or deleterious in another. In addition, we uncover a striking enrichment for epistasis among beneficial variants — a pattern of fundamental importance that has not been previously observed. The identified epistatic variants reflect physiological differences between the strains, yielding novel insight into the mechanisms underlying complex traits. In summary, this work lays the foundation for building a framework to understand molecular epistasis genome-wide, advancing our knowledge towards a complete genotype-phenotype map.
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 | Ang, Moh Lik Roy |
|---|---|
| Degree supervisor | Fraser, Hunter B |
| Thesis advisor | Fraser, Hunter B |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Petrov, Dmitri Alex, 1969- |
| Thesis advisor | Sherlock, Gavin |
| Degree committee member | Bassik, Michael |
| Degree committee member | Petrov, Dmitri Alex, 1969- |
| Degree committee member | Sherlock, Gavin |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Roy M. L. Roy Ang. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/ht108fn9466 |
Access conditions
- Copyright
- © 2022 by Moh Lik Roy Ang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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