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Authors: Yang, Lu
Advisors: Andolfatto, Peter
Contributors: Ecology and Evolutionary Biology Department
Keywords: adaptation
gene editing
sodium potassium ATPase
Subjects: Evolution & development
Issue Date: 2020
Publisher: Princeton, NJ : Princeton University
Abstract: The rate of adaptation is believed to be limited by mutational size, epistasis, and negative pleiotropic effect, and gene duplication relaxes the constraints by providing evolutionary novelty. However, it is difficult to evaluate how these factors collectively shape adaptation in different ecological and physiological contexts. An effective way to characterize the dynamics of adaptation and assess the predictability of evolutionary trajectories is to study cases of convergent evolution at the molecular level. In my dissertation research, I develop a paradigm which examines large assemblages of insects and vertebrates that face a common selective pressure. Specifically, I focus on the evolution of resistance to a category of toxins called cardiac glycosides (CGs), which target the alpha subunit of Na+, K+-ATPase, an essential enzyme for a variety of biological processes. Some organisms have evolved the ability to utilize food sources that contain CGs and even sequester CGs for their own defense, potentially through target-site insensitivity of Na+, K+-ATPase. In Chapter Two, I expand the existing survey of herbivorous insects adapted to CG-producing plants. In a meta-analysis of data from six insect orders, I identify pleiotropy as a major factor limiting the rate of adaptation and implicate gene duplication as a primary facilitator that overcomes these constraints. In Chapter Three, I document distinct toxin resistance strategies used by predatory fireflies, which have duplicated the alpha subunit of Na+, K+-ATPase, and they firefly prey which main a single copy of the gene. I then use genome-editing experiments to demonstrate how pleiotropic constraints are overcome by gene duplication in the predator and identify a new determinant of toxin-insensitivity in the prey. In Chapter Four, we describe a trans-specific duplication of the alpha subunit of Na+, K+-ATPase in frogs that prey on CG-producing toads. This duplication experiences a phenomenon called “concerted evolution” that allows us to identify 12 amino acid substitutions that we infer to be important for fitness. We then use protein engineering experiments to show how these 12 substitutions are critical for both CG-resistance and interact epistatically to maintain proper protein function. Overall, these chapters combine evolutionary and molecular genetics methods to show how epistasis and pleiotropy constrain the path of adaptive evolution of CG resistance in diverse animals.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Ecology and Evolutionary Biology

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