Evolutionary rate heterogeneity in proteins with long disordered regions

Area of Science:

• Protein science
• Molecular evolution
• Structural biology

Background:

• The prevailing view posits that a defined 3-D structure is essential for protein function.
• However, intrinsically disordered proteins (IDPs) lack stable structures yet perform vital cellular roles.
• Anecdotal evidence suggests IDPs may evolve more rapidly than ordered proteins.

Purpose of the Study:

• To empirically test whether intrinsically disordered protein regions evolve at a faster rate than ordered protein regions.
• To investigate the relationship between protein disorder, sequence evolution, and protein function.

Main Methods:

• Comparative analysis of pairwise genetic distances between ordered and disordered regions.
• Examination of 26 protein families with characterized disordered regions (≥30 residues).

Main Results:

• Disordered regions evolved significantly faster than ordered regions in 19 out of 26 protein families.
• No significant difference in evolutionary rates was observed in 5 families.
• Disordered regions evolved significantly slower in 2 families, including DNA-binding sites.

Conclusions:

• Intrinsically disordered protein regions exhibit variable evolutionary rates, often evolving more rapidly than ordered counterparts.
• Functions of rapidly evolving disordered regions are diverse, including binding sites and linkers.
• Further research is required to elucidate the factors driving the variability in evolutionary rates of disordered and ordered protein segments.