Past, present, and future of sequence alignment

The aim of comparative genomics is to study variation between genomes to gain a deeper understanding of the forces and processes that shape them. In this dissertation, I chronicle my involvement at the dawn of mammalian comparative genomics when the second and third mammalian genome were sequenced and analyzed. This dissertation will cover the methods used to align the mouse and rat genomes to the human genome and how these methods enabled me to analyze the process of neutral evolution with unprecedented fidelity. This new wealth of data enabled the observation of large and fine scale variations in the processes of neutral evolution. My results and observations have impacted the field of comparative genomics and continue to be used in current literature. This dissertation also presents my work applying alignment algorithms to solve very large alignment problems. Continuing developments in alignment algorithms have produced more sophisticated and principled alignment methods. These new algorithms are often computationally expensive. I developed two general methods that harness the power of parallelization and enable these expensive methods to be applied to large, biologically relevant problems.