AWSEM Studies of Cyclophillin A Evolving Pseudogenes

Pseudogenes are defined as nonfunctional relatives of their protein coding parent genes that give us a glimpse at former coding genes that were under selection pressure, and now are neutrally evolving. By looking at multiple pseudogenes of a parent gene, we can see snapshots of evolution with dying genes and genes that are regaining function. This research aims to analyze and compare the energetic landscapes of pseudogenes and their respective parents in a way that has never been done in literature. Five pseudogene candidates demonstrating various levels of activity were obtained from the biologically important Cyclophilin A protein family. AWSEM Suite was chosen to predict the pseudogene protein structures which was compared directly against the parent gene structure. Our analysis of the different pseudogene structures found high similarity when compared to the parent crystal structure. Our analysis of the evolutionary energies showed that energies are lower between pseudogenes and parents as expected. We conclude that pseudogenes still maintain the structure of their parent gene (have similar physical energies) despite mutations and varying activity levels and that pseudogenes have more unstable evolutionary energies compared to their parents. This research only explored one protein family that had a complete protein family structure and multiple pseudogenes for testing. In the future, research should be expanded to more protein families and analyze the full sequence of pseudogenes. This project was completed with contributions from Hana Jaafari from Rice University.