Biophysical models of protein evolution: Understanding the patterns of evolutionary sequence divergence

For decades, rates of protein evolution have been interpreted in terms of the vague concept of \"functional importance\". Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic mis-folding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in pr