Molecular Mechanisms of Protein Evolution
How has the repertoire of remarkably diverse protein functions evolved in nature? We are interested in understanding the evolutionary dynamics of biological molecules and systems and, in particular, how evolution has generated the diverse array of genes (proteins and enzymes) that cohesively work together to function as complex cells and organisms. Current knowledge of the molecular mechanisms of protein evolution is limited: What drives the generation of a new protein function? How many mutations are required to change one enzyme to another? Is the order of mutations important for the course of evolution? What makes a sequence (gene) particularly “evolvable” for the generation of new functions? We aim to understand the molecular basis of evolution, i.e., how a mutation causes structural and biophysical changes to a protein, and eventually leads to functional changes. Understanding the molecular mechanisms of evolution addresses, not only 3 billion years of evolutionary history on earth, but also on-going evolution of extant proteins (e.g., drug resistance, and the degradation of xenobiotic compounds).
Our scientific approach is interdisciplinary, we employ a wide variety of research techniques, including molecular and structural biology, protein biochemistry and biophysics, and bioinformatics. We extensively employ an “experimental evolution” approach, a technique that is used to mimic evolutionary processes in the laboratory, and to reconstruct the evolutionary trajectories of biological molecules. In doing so, we study the molecular mechanisms of protein evolution that underlie the diverse range of functions that are observed in modern enzymes. Furthermore, we utilize and apply the knowledge gained from evolutionary biochemistry to generate and engineer novel proteins, metabolic pathways and organisms.
