Evolution and disorder

Abstract

The evolution of disordered proteins or regions of proteins differs from that of ordered proteins because of the differences in their sequence composition, intramolecular contacts, and function. Recent assessments of disordered protein evolution at the sequence, structural, and functional levels support this hypothesis. Disordered proteins have a different pattern of accepted point mutations, exhibit higher rates of insertions and deletions, and generally, but not always, evolve more rapidly than ordered proteins. Even with these high rates of sequence evolution, a few examples have shown that disordered proteins maintain their flexibility under physiological conditions, and it is hypothesized that they maintain specific structural ensembles.

Figure 1

Disordered proteins have more insertions and/or deletions than ordered proteins. Homologues within families of structurally-characterized disordered regions or completely ordered proteins were aligned [15], and the alignments were compared at various levels of percent identity for the number of gaps of any length within the alignment. The box plots show median (dark bar), quartiles ( grey boxes), 1.5x the interquartile range (dashed lines) and means that were outside of this range (circles). There are significantly more gaps within disordered regions of proteins than within the ordered proteins at all levels of percent identity (Wilcoxon rank sum tests, p<0.01). (A. K. Johnson, MS Thesis: Comparing models of evolution between ordered and disordered proteins, University of Idaho, 2008.)

Figure 2

Thermodynamic cycle showing the relationship between induced folding (IF) and conformational selection (CS) binding mechanisms. A representative IDP structure is shown in red. This structure can either bind with low affinity and then fold into the native structure (IF) or can fold into the native structure and then bind (CS). Figure adapted from [54].