We use integrative and comparative approaches to make fundamental discoveries in the fields of phylomedicine, molecular evolution and functional genomics. The common theme of our research is the use of comparative analysis to reveal genome differences that are outcomes of natural selection on novel mutations. The taxonomic breadth of our studies spans the tree of life and the timescale of mutation transmission ranges from generation to generation and cell division to cell division. The resulting patterns of evolutionary conservation and divergence form the basis of a Pattern-Process-Prediction-Product (P4) approach that enables us to conduct research investigations ranging from scaling the tree of life to time (Timetree of Life) to forecasting disruptive mutations found in personal germline and somatic genomes (Phylomedicine). In pursuit of these biological discoveries, we are developing new statistical methods and computer algorithms to quickly analyze large-scale datasets. We have also developed and disseminated many high-impact software tools (MEGA) and databases (TimeTree, FlyExpress, www.myPEG.info).