CPM Seminar

Biophysical models of protein evolutionary dynamics

Alexander Morozov

Rutgers University

High-throughput sequencing and other modern tools of molecular biology have made it possible to track evolution in unprecedented detail. As a result, we are now closer to understanding fundamental principles involved in evolutionary dynamics.

Many cellular functions are underpinned by protein-protein interactions, which mediate such diverse processes as metabolism, immune response, signaling, and DNA replication. These interactions can rapidly evolve in response to perturbations in the protein physico-chemical environment, such as changes in the concentration or chemical composition of protein-binding ligands. Here I will focus on how structural coupling between protein folding and binding free energies gives rise to evolutionary coupling between the traits of folding stability and binding strength. Using evolutionary models inspired by protein biophysics, I will show how these protein traits can emerge as evolutionary spandrels, that is, features that are by-products of selection on some other trait, rather than direct targets of adaptation. In particular, proteins can evolve strong binding interactions that have no functional role but merely serve to stabilize the protein if its misfolding is deleterious. Furthermore, such proteins may have divergent fates, evolving to bind or not to bind their targets depending on random mutational events. Our model may explain the abundance of apparently non-functional protein-protein interactions observed in high-throughput screens. Overall, our findings lead to improved understanding of evolution of proteins and protein interaction networks.