RT Journal Article
SR Electronic
T1 The role of evolutionary selection in the dynamics of protein structure evolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 059741
DO 10.1101/059741
A1 Amy I. Gilson
A1 Ahmee Marshall-Christensen
A1 Jeong-Mo Choi
A1 Eugene I. Shakhnovich
YR 2016
UL http://biorxiv.org/content/early/2016/10/25/059741.abstract
AB Homology modeling is a powerful tool for predicting a protein’s structure. This approach is successful because proteins whose sequences are only 30% identical still adopt the same structure, while structure similarity rapidly deteriorates beyond the 30% threshold. By studying the divergence of protein structure as sequence evolves in real proteins and in evolutionary simulations, we show that this non-linear sequence-structure relationship emerges as a result of selection for protein folding stability in divergent evolution. Fitness constraints prevent the emergence of unstable protein evolutionary intermediates thereby enforcing evolutionary paths that preserve protein structure despite broad sequence divergence. However on longer time scales, evolution is punctuated by rare events where the fitness barriers obstructing structure evolution are overcome and discovery of new structures occurs. We outline biophysical and evolutionary rationale for broad variation in protein family sizes, prevalence of compact structures among ancient proteins and more rapid structure evolution of proteins with lower packing density.