Honors Theses and Capstones
Date of Award
Spring 2024
Project Type
Senior Honors Thesis
College or School
COLSA
Department
Department of Molecular, Cellular, and Biomedical Sciences
Program or Major
Biomedical Sciences: Medical and Veterinary Sciences
Degree Name
Bachelor of Science
First Advisor
David Plachetzki, Ph.D.
Abstract
Apoptosis is a highly regulated process that plays a critical role in the development and maintenance of multicellular organisms. It is a highly regulated process involving signaling pathways that lead to the activation of caspases, the main executioners of programmed cell death. Although essential for various physiological and biological processes, dysregulation of apoptosis can contribute to various diseases, including cancer. The p53 protein plays a crucial role in regulating apoptosis, acting as a tumor suppressor by activating genes involved in cell cycle arrest, DNA repair, and programmed cell death. The complex interplay between p53 and apoptosis is essential for maintaining cellular homeostasis and preventing diseases like cancer. Interestingly, some organisms, like ecdysozoans (characterized by their ability to molt their external cuticle), have evolved a suppressed version of apoptotic pathways that emerged within their molting genes without exhibiting increased rates of cancer. Therefore, selection has acted in specific ways within the TP53 gene among ecdysozoans, differing from non-ecdysozoans. Changes in the DNA-binding domain of the p53 gene can alter the cellular pathways it regulates. That illustrates how genes can evolve to become less necessary and potentially be lost over time through the process of relaxed selection. Therefore, the research aimed at studying the differences in selection observed within the TP53 gene in ecdysozoans, compared to non-ecdysozoans, to observe what specific domains are driving the divergence in apoptotic pathways between these two groups. The key findings of this study indicate that the p53-binding domain, which is responsible for mediating interactions with cellular proteins, has been the primary target of intense selective forces. These forces have played a pivotal role in shaping the differences in apoptotic pathways between ecdysozoans and non-ecdysozoans. Conversely, the N-terminal and C-terminal domains of the TP53 gene appear to be less critical for the core tumor suppressor functions of p53. The data revealed that ecdysozoan species, such as arthropods and nematodes, have experienced more relaxed selection pressures on the p53 gene compared to other metazoan lineages. This observation suggests that the TP53 gene in ecdysozoans, particularly those that undergo ecdysis, has been subject to stronger evolutionary pressure and diversification to integrate with the molting genes and pathways. Continued investigation into the evolutionary dynamics and functional significance of the p53 gene, as revealed by this study, can further inform and guide these important advancements in the field of oncology.
Recommended Citation
Bodenrader, Joseph Brian, "Exploring the Evolutionary Dynamics of the p53 Gene in Ecdysozoans: Implications for Cancer Biology and Genetic Regulation" (2024). Honors Theses and Capstones. 807.
https://scholars.unh.edu/honors/807