Rapid evolution exposes the boundaries of domain structure and function in natively unfolded FG nucleoporins

Nups) function at the nuclear pore complex (NPC) to fa-cilitate nucleocytoplasmic transport. In Saccharomyces cerevisiae, each FG Nup contains a large natively un-folded domain that is punctuated by FG repeats. These FG repeats are surrounded by hydrophilic amino acids (AAs) common to disordered protein domains. Here we show that the FG domain of Nups from human, fly, worm, and other yeast species is also enriched in these disorder-associated AAs, indicating that structural disorder is a conserved feature of FG Nups and likely serves an impor-tant role in NPC function. Despite the conservation of AA composition, FG Nup sequences from different species show extensive divergence. A comparison of the AA sub-stitution rates of proteins with syntenic orthologs in four Saccharomyces species revealed that FG Nups hav