All ETDs from UAB

Advisory Committee Chair

Elliot J Lefkowitz

Advisory Committee Members

William J Britt

Jeffrey A Engler

Jamil S Saad

Robert W Thacker

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Members of the Poxviridae family of viruses have experienced several different evolutionary mechanisms to arrive at their large genomes, diverse host range, and complex replication cycle that we see today. Our work has focused on the identification of gene truncation, fragmentation, and deletion events. We have used genomic sequences for representative species throughout the Poxviridae family as our data set, and correctly annotated the gene set for each virus. We found that the number of truncated, fragmented, or missing genes in a genome is highly variable. We also identified the nucleotide changes which lead to gene loss, called early stop mutations, and we found that in the Orthopoxvirus genus, the number of early stop mutations in a genome is inversely proportional to the length of the genome. In several of the poxviruses, early stop mutations are associated with microsatellites, suggesting that the increased mutation rate at these short repeats plays a role in the introduction of mutations that affect the gene content of an isolate. Our investigation has led to new details on the role and mechanisms of gene content variation in the poxviruses, and adds to our understanding of the evolutionary history, pathogenesis, and biology of these viruses.

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