SYNERGIZING GENETIC ENGINEERING AND EVOLUTIONARY BIOLOGY: ANIMAL-BASED LINEAGE TRACKING TO STUDY ADAPTIVE MUTATIONS
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Date
2024-03-25
Authors
Stevenson, Zachary
Journal Title
Journal ISSN
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Publisher
University of Oregon
Abstract
The fitness effects of new mutations are one of the central drivers of evolutionary change. Mutation is the ultimate source of novel genetic diversity, yet only a small fraction of new mutations provides an adaptive advantage. Additionally, many new adaptive mutations provide only a slight advantage and are challenging to identify and quantify their selection coefficient. Furthermore, a given mutation may be advantageous in one environment and disadvantageous in another environment. Natural selection acts upon the phenotype produced by the new mutation and if adaptive, the mutation can increase in frequency. Evolution acts though the lineage–the fundamental unit of evolution–because it is the lineage which changes overtime in response to selection. Over the past 150 years a robust and comprehensive set of theory has been developed around evolutionary biology and adaptive mutations. However, comprehensive estimation of the fitness effects of new mutations has remained challenging, but recent developments in genetic engineering open new opportunities to significantly advance the field. Within this dissertation, I present several novel approaches for editing the genome using a large genomic library, which allows the implementation of barcoding approach for evolutionary lineage tracking in an animal system for the first time. I apply this methodology to measure the fitness of a known Ivermectin resistant strain of Caenorhabditis elegans in what is the largest animal experimental evolution to date and highlight important new directions in evolution and genomics that this new approach allows.
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Keywords
CRISPR, Evolution, Genetics, High-throughput, Synthetic, TARDIS