Pseudogene Energy Landscapes: A Frustrating Case of Neutral Evolution?
Master of Science
Functional proteins are optimized by evolution over the course of millions of years to quickly fold into their native three-dimensional structures. Evolution exerts a strong selection pressure on protein sequences to maintain foldability and stability, resulting in minimally frustrated folding energy landscapes. Pseudogenes, genetic elements homologous to coding genes, are evolutionary relics of the genome experiencing little or no selection pressure. Pseudogenes are ideal candidates to examine the energy landscapes of devolving genetic elements. This thesis project is the first to quantify the “evolutionary” energies, measured with Direct Coupling Analysis (DCA), of pseudogenes across multiple protein families. The DCA energies of pseudogenes, their parent proteins, and other proteins within each family were examined, and the results of these studies suggest that pseudogenes become less well optimized from an evolutionary standpoint over time. Indeed, analyses of the DCA energies of mutants generated in silico indicated that pseudogenes devolve just as rapidly as completely randomly mutated parent genes.
pseudogenes; AWSEM; DCA; neutral evolution