Genetic interactions distinguish different roles of disorder. (a) Percentage of disordered residues of yeast proteins by their number of GIs. (b) Multi-functionality (see Materials and methods) for disordered and structured GI hubs and non-hubs. Hubs are genes in the top 90th percentile (above 90 interactions) of GIs while non-hubs are in the bottom 50th percentile (below 15 interactions). (c) Evolutionary constraint on sequence (dN/dS ratio) on hubs and non-hubs. In both cases disordered proteins have a significantly higher dN/dS than structured proteins. (d) Evolutionary constraint measured by the presence of orthologs in other yeast species (phylogenetic persistence). While disordered non-hubs are less conserved than structured non-hubs, the disordered hubs are as conserved as structured hubs. P-values were computed with a Wilcoxon test, and error bars represent boot-strapped 95% confidence intervals.