Functions of intrinsically disordered proteins through evolutionary lenses.

Protein sequences are the result of an evolutionary process that involves the balancing act of experimenting with novel mutations and selecting out those that have an undesirable functional outcome. In the case of globular proteins, the function relies on a well-defined conformation, therefore, there is a strong evolutionary pressure to preserve the structure. However, different evolutionary rules might apply for the group of intrinsically disordered regions and proteins (IDR/IDPs) that exist as an ensemble of fluctuating conformations. The function of IDRs can directly originate from their disordered state or arise through different types of molecular recognition processes. There is an amazing variety of ways IDRs can carry out their functions, and this is also reflected in their evolutionary properties. In this chapter we give an overview of the different types of evolutionary behavior of disordered proteins and associated functions in normal and disease settings.