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- All Subjects: Genomics
- Genre: Masters Thesis
- Creators: Raborn, Randolph T
- Creators: Tollis, Marc
Description
Cancer is a disease which can affect all animals across the tree of life. Certain species have undergone natural selection to reduce or prevent cancer. Mechanisms to block cancer may include, among others, a species possessing additional paralogues of tumor suppressor genes, or decreasing the number of oncogenes within their genome. To understand cancer prevention patterns across species, I developed a bioinformatic pipeline to identify copies of 545 known tumor suppressor genes and oncogenes across 63 species of mammals. I used phylogenetic regressions to test for associations between cancer gene copy numbers and a species’ life history. I found a significant association between cancer gene copies and species’ longevity quotient. Additional paralogues of tumor suppressor genes and oncogenes is not solely dependent on body size, but rather the balance between body size and longevity. Additionally, there is a significance association between life history traits and genes that are both germline and somatic tumor suppressor genes. The bioinformatic pipeline identified large tumor suppressor gene and oncogene copy numbers in the naked mole rat (Heterocephalus glaber), armadillo (Dasypus novemcinctus), and the two-fingered sloth (Choloepus hoffmanni). These results suggest that increased paralogues of tumor suppressor genes and oncogenes are these species’ modes of cancer resistance.
ContributorsSchneider-Utaka, Aika Kunigunda (Author) / Maley, Carlo C (Thesis advisor) / Wilson, Melissa A. (Committee member) / Tollis, Marc (Committee member) / Arizona State University (Publisher)
Created2019
Description
Regulation of transcription initiation is a critical factor in the emergence of diverse biological phenotypes, including the development of multiple cell types from a single genotype, the ability of organisms to respond to environmental cues, and the rise of heritable diseases. Transcription initiation is regulated in large part by promoter regions of DNA. The identification and characterization of cis-regulatory regions, and understanding how these sequences differ across species, is a question of interest in evolution. To address this topic, I used the model organism Daphnia pulex, a well-characterized microcrustacean with an annotated genome sequence and selected a distribution of well-defined populations geographically located throughout the Midwestern US, Oregon, and Canada. Using isolated total RNA from adult, female Daphnia originating from the selected populations as well as a related taxon, Daphnia pulicaria (200,000 years diverged from D. pulex), I identified an average of over 14,000 (n=14,471) promoter regions using a novel transcription start site (TSS) profiling method, STRIPE-seq. Through the identification of sequence architecture, promoter class, conservation, and transcription start region (TSR) width, of cis-regulatory regions across the aforementioned Daphnia populations, I constructed a system for the study of promoter evolution, enabling a robust interpretation of promoter evolution in the context of the population-genetic environment. The methodology presented, coupled with the generated dataset, provides a foundation for the study of the evolution of promoters across both species and populations.
ContributorsSnyder, Shannon (Author) / Lynch, Michael (Thesis advisor) / Harris, Robin (Committee member) / Raborn, Randolph T (Committee member) / Wideman, Jeremy (Committee member) / Arizona State University (Publisher)
Created2020