dN/dS values compared between the Ste50 IDR, the RA domain, and the SAM domain. The dN/dS value for the IDR is higher (0.18) compared with the SAM (0.12) and RA (0.01) domains. However, much of the sequence variation in IDRs comes from the high rates of non–frame-shifting insertions and deletions that we find in these regions (9–13), which would not be captured in the dN/dS analysis. Therefore, dN/dS is likely to overestimate the constraint in disordered regions. Error bars represent 1.96 SE.