**4. Conclusions**

In human and mouse, the SDs of immune-related proteins evolve at a high rate which comes close to that of the IDRs. This observation indicates that positive selection operates on both SDs and IDRs of the encoded proteins in many immune-related genes. Comparatively high evolution in SDs is also observed in non-immune-related secreted proteins in human and mouse, and to a lesser extent in thale cress, but not in budding yeast. Thus accelerated evolution in SDs as well as in IDRs contributes to rapid evolution of extracellular proteins in mammals.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1422-0067/19/12/3860/s1.

**Author Contributions:** Conceptualization, K.H.; Methodology, K.H.; Software, H.A., T.N., S.F.; Validation, K.H., H.A., T.N., S.F.; Formal Analysis, K.H.; Investigation, K.H., H.A.; Resources, K.H.; Data Curation, K.H.; Writing-Original Draft Preparation, K.H.; Writing-Review & Editing, K.H.; Visualization, K.H.; Supervision, K.H.; Project Administration, K.H.; Funding Acquisition, K.H.

**Conflicts of Interest:** The authors declare no conflict of interest.
