Undergraduate Honors Theses

Thesis Defended

Spring 2018

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Sara Sawyer

Second Advisor

Brian DeDecker

Third Advisor

Alison Vigers

Abstract

Interferons and the genes they upregulate are involved in many diverse mechanisms that suppress viral replication. Upon cellular recognition of a virus, interferons are expressed, secreted, and taken up by neighboring cells. Interferons then stimulate the expression of hundreds of genes that target every step of a viral life cycle. In turn, viruses have evolved strategies to inhibit the interferon response by evading recognition, impairing signaling, or hindering restrictive functions of proteins that are expressed in response to interferon signaling. Genes that induce the response and interferon-stimulated genes must evolve in turn to maintain an effective defense against viruses in spite of high viral mutation rates. This evolutionary battle for the upper hand creates a situation of coevolution. In this study, I have analyzed genes that induce the interferon response and interferon-stimulated genes for signatures of enhanced natural selection. I have detected loci which have significantly elevated rates of non-synonymous (amino acid altering) substitutions. Interestingly, the highest signal for elevated rates of non-synonymous mutations was found in interferon-stimulated genes, and not induction genes when compared to a set of random genes. Evolution that favors increased rates of non-synonymous mutations may indicate that viruses are intensifying selective pressure for mutations, especially in interferon-stimulated genes. I experimentally test this hypothesis with several primate alleles of a rapidly evolving interferon-stimulated gene and the viral protein it targets. Alleles of this gene from Humans, Chimpanzees, and Gibbons are able to degrade the viral protein to some extent. Further testing on this degradation phenotype is required.

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