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Genetic network rewiring between distantly related eukaryotic species

Title:

Genetic network rewiring between distantly related eukaryotic species

Pereira, Vanessa (2024) Genetic network rewiring between distantly related eukaryotic species. Masters thesis, Concordia University.

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Abstract

Genetic interactions occur when a combination of mutations in different genes results in an unexpected phenotype based on the combined effects of individual single mutants. Synthetic lethality represents an extreme example of a genetic interaction resulting in lethal double mutant from the combination of viable single mutants. The knowledge of the genetic interactions that underlie conditional gene essentiality across species, whereby a gene which is required for viability in one species is dispensable in another has remained elusive. In this thesis, I investigated digenic interactions that underlie conditional essentiality, and the trigenic interactions that underlie conditional synthetic lethality in distantly related eukaryotes to understand the principles of genetic network conservation. First, I used literature curation to identify conditional essential genes and their synthetic lethal interactions across S. cerevisiae, S. pombe, C. elegans and H. sapiens. I applied functional enrichment analysis and demonstrated that conditional essential genes are rewired by functionally related and specific synthetic lethal digenic interactions. Second, I identified synthetic lethal double mutants in S. cerevisiae that were viable in S. pombe. I constructed and screened 14 conditional essential double mutants and corresponding 24 single mutant query strains using trigenic Synthetic Genetic Array (τ-SGA) to identify trigenic interactions. I found that similar to single mutants, conditional synthetic lethal double mutants were rewired by functionally related trigenic interactions. Ultimately, understanding the rewiring of gene essentiality by genetic interactions sheds light on genome evolution and synthetic lethal therapies for human disease.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Pereira, Vanessa
Institution:Concordia University
Degree Name:M. Sc.
Program:Biology
Date:27 November 2024
Thesis Supervisor(s):Kuzmin, Elena
ID Code:994946
Deposited By: Vanessa Pereira
Deposited On:17 Jun 2025 17:42
Last Modified:17 Jun 2025 17:42
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