Year: 2014
Type: dissertation
Abstract: The sequence of the genome gradually evolves, and such changes can affect the function of the genes encoded within. Here I try to understand the causes and consequences of changes in gene function between related species, particularly in Caenorhabditis nematodes. The goal of the first section of my thesis is to compare biological gene function of 1-1 orthologs by using loss of function phenotypes in C. elegans and C. briggsae. I did this by constructing and screening an RNA interference (RNAi) library in C. briggsae and comparing these RNAi phenotypes to those in C. elegans. This approach found 91 examples of orthologs with different in vivo functions, around 7% of the genes screened. For one of these examples, sac-1, I was able to explain the different biological function by a difference in molecular function, in this case by a difference in gene expression. Given the extremely high phenotypic similarity of these two species I hypothesize that many of these examples of different RNAi phenotypes likely represent cases of changes in gene function which have preserved the developmental phenotypes of the animal due to high levels of stabilizing selection, a model known as Developmental System Drift. In support of this, I found several cases where a phenotype is not present in the C. briggsae copy of an ortholog, but it is present in another related family member, suggesting that this related gene has taken over the function of the original gene in C. briggsae.I also found that recently evolved genes are enriched for having different RNAi phenotypes, which led me to consider what could explain their rapid rate of evolution of in vivo function. By measuring the co-expression of novel genes to genes in different molecular pathways, I was able to construct a series of features which could accurately predict which novel genes become essential. An analysis of this model showed that co-expressions to ancient, essential pathways is highly predictive of a novel gene acquiring an essential function. These results supported a picture of how novel genes become integrated into cellular networks, and subsequently are preserved by evolutionary forces.
Source: TSpace (University of Toronto)
Author: Adrian J. Verster
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2598535655