Evolution of protein structure and function: de novo and intrinsically disordered proteins

It was long believed that the proteins we find today all derive from ancestral variants in the deep past.

Then the ubiquitous presence of intrinsically disordered regions in proteins was appreciated, and that they can emerge and change relatively fast on an evolutionary timescale. Recent studies now show that emergence of completely new (de novo) proteins is common across all organisms.

These discoveries raise several outstanding questions: Are new proteins predominantly intrinsically disordered or do they populate folded states? Can we assume that proteins with a similar fold are homologous? What are the biological roles of de novo proteins? Are emergence of new proteins and rapid protein evolution important evolutionary mechanisms as a source of innovation?

Indeed, intrinsically disordered regions in proteins usually evolve faster than the folded parts and as such are also a source of de novo sequence and functionality.

The significance lies in finding fundamental concepts about structure, folding and evolution of de novo and rapidly evolving intrinsically disordered protein regions, and linking structure-folding with evolution of function to, perhaps, obtain the full molecular history from gene birth to function. The 4-year project involves a combination of bioinformatics, protein chemistry and structural- and biophysical methods.

It is performed together with PhD students and several collaborators.