Adaptive evolution, sex-linkage, and gene conversion in the voltage-gated sodium channels of toxic newts and their snake predators

dc.contributor.authorGendreau, Kerryen
dc.contributor.committeechairMcGlothlin, Joel W.en
dc.contributor.committeememberUyeda, Josef C.en
dc.contributor.committeememberBelden, Lisa Kayen
dc.contributor.committeememberMims, Meryl C.en
dc.contributor.committeememberHaak, David C.en
dc.contributor.departmentBiological Sciencesen
dc.description.abstractUnderstanding how genetic changes ultimately affect morphology and physiology is essential for understanding and predicting how organisms will adapt to environmental changes. Although most traits are complex and involve the interplay of many different genetic loci, some exceptions exist. These include the convergent evolution of tetrodotoxin resistance in snakes, which has a simple genetic basis and can be used as a model system to investigate the genetic basis of adaptive evolution. Tetrodotoxin is a potent neurotoxin used as a chemical defense by various animals, including toxic newts. Snakes have evolved resistance through mutations in voltage-gated sodium channels, the protein targets of tetrodotoxin, sparking an evolutionary arms race between predator and prey. In this dissertation, I describe how genomic rearrangements have led to sex-linkage of four of the voltage-gated sodium channel genes in snakes and compare allele frequencies across populations and sexes to make inferences about how sex linkage has influenced the evolution of resistance in garter snakes. By measuring gene expression in different snake tissues, I show that three of these sex-linked sodium channel genes are dosage compensated in embryos, adult muscle, and adult brain. In contrast, two channels show sexual dimorphism in their expression levels in the heart, which may indicate differences in dosage compensation among tissues. I then use comparative genomics to track the evolutionary history of tetrodotoxin resistance across all nine sodium channel genes in squamate reptiles and show how historical changes have paved the way for full-body resistance in certain snakes. Finally, I use targeted sequence capture to obtain the sodium channel sequences of salamanders and show evidence that tetrodotoxin self-resistance in toxic newts was likely accelerated through gene conversion between resistant and non-resistant sodium channel paralogs. Together, these results illustrate parallelism in evolutionary mechanisms and processes contributing to the appearance of an extreme and complex trait that arose independently in two distinct taxa separated by hundreds of millions of years.en
dc.description.abstractgeneralWestern North America is the site of an ongoing battle between highly toxic species of salamanders (toxic newts) and their garter snake predators. In certain regions, garter snakes have countered newt defenses by evolving resistance to their toxins, and the newts have become more toxic in response. This interaction has been the focus of scientists for decades because it teaches us about the ways in which animals can respond to changes in their environment. In living organisms, DNA is used a blueprint to determine the ultimate traits that are expressed (e.g., whether an organism will have five fingers or four, or whether it will be resistant or sensitive to a toxin). By comparing DNA sequences of different life forms, we are beginning to understand the rules that determine how these blueprints are read and how they can change over time. Because life is built upon the same basic building blocks (DNA, mRNA, and proteins), information about this snake-newt system can be used to understand the way that other systems, such as humans and pathogens, might interact. In my dissertation, I compare DNA sequences from snakes and lizards to identify the history of changes leading to the extreme toxin resistance in the garter snakes. I show that toxin resistance began hundreds of millions of years ago, with all lizards having a low baseline level of resistance, and that resistance built up slowly in the lineages leading to garter snakes. I also show that because of DNA rearrangements, female snakes have fewer copies of some of the genes involved in resistance, and this may have led to differences among the sexes. Lastly, I compare DNA sequences among salamanders, revealing a similar pattern to that in snakes and lizards. Specifically, newts have evolved self-resistance to their own toxin, and this has happened gradually over hundreds of millions of years, with all salamanders having some toxin resistance. I also show that an unusual process occurred within the DNA of toxic newts, resulting in a rapid change from toxin sensitivity to toxin resistance in some genes. Taken together, this work helps advance our understanding of the processes and limitations that determine how organisms can function and change over time.en
dc.description.degreeDoctor of Philosophyen
dc.publisherVirginia Techen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.subjectmolecular evolutionen
dc.subjecttoxin resistanceen
dc.subjectgene conversionen
dc.subjectvoltage-gated sodium channelen
dc.titleAdaptive evolution, sex-linkage, and gene conversion in the voltage-gated sodium channels of toxic newts and their snake predatorsen
dc.typeDissertationen Sciencesen Polytechnic Institute and State Universityen of Philosophyen


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