Protein Folding Sculpting Evolutionary Change

Abstract

Our work suggests that the forces that govern protein folding exert a profound effect on how genotypes are translated into phenotypes, and that this in turn has strong effects on evolutionary processes. Molecular chaperones, also known as "heat shock proteins" (Hsps), promote the correct folding and maturation of many other proteins in the cell.Hsp90 is an abundant and highly specialized chaperone that works on a particularly interesting group of client proteins: metastable signal transducers that are key regulators of a broad spectrum of biological processes. Such proteins often have evolved to finish folding only when they have received a specific signal, such as the binding of a ligand or a post-translational modification. Importantly, the folding of Hsp90 clients is particularly sensitive to changes in the external and internal environment of the cell. Therefore, Hsp90 is uniquely positioned to couple environmental contingencies to the evolution of new traits. Our work has helped to define two mechanisms by which Hsp90 might influence the acquisition of new phenotypes. First, by robustly maintaining signaling pathways, Hsp90 can buffer the effects of mutations in those pathways, allowing the storage of cryptic genetic variation that is released by stress. In this case, when the Hsp90 buffer is compromised by environmental stress, new traits appear. These traits can also be assimilated, so that they become manifest even in the absence of stress, when genetic recombination and selection enrich causative variants in subsequent generations.Second, Hsp90 can potentiate the effects of genetic variation, allowing new mutations to

Microsatellite-encoded domain in rodent Sry functions as a genetic capacitor to enable the rapid evolution of biological novelty

“…Such variation could then have been unmasked by microsatellite instability leading to truncation of the glutamine-rich domain below its critical threshold. This model extends the paradigm of a genetic capacitor as defined by heat shock protein 90 (Hsp90) (27,28). Because Hsp90 buffers the misfolding of proteins regulating metazoan development (thereby conferring interim stability to gene regulatory networks), discharge of the Hsp90 capacitor may underlie rapid morphological evolution as documented in the fossil record (64).…”

“…We envisage that variation in rodent Sry-suppressed or unmasked at the protein level by an unstable CAG-encoded glutamine-rich domain (25)-has been a source of evolutionary innovation: an historical contingency of genomic dynamics leading to divergence of a master switch and even to its anomalous disappearance (18,26). The Sry glutamine-rich domain, thus functioning as a genetic capacitor (27,28), has fostered the rapid generation of biological novelty in the radiation of a mammalian taxon.…”

Reconstructing the Fungal Tree of Life Using Phylogenomics and a Preliminary Investigation of the Distribution of Yeast Prion-Like Proteins in the Fungal Kingdom

“…Currently, there is a lively debate in the yeast prion field as to whether the [PSI ? ] prion is a ''disease'' of yeast or provides a potential benefit to yeast cells in times of stress (for recent reviews, see Lindquist 2009;Wickner et al 2010). The conservation pattern of the Sup35 prion domain depicted in Fig.…”

In vivo aspects of protein folding and quality control

“…Prolonged binding of nonnative protein to Hsp70 may favor degradation. Figure modified from (13).RESEARCH | REVIEWon June 30, 2016 http://science.sciencemag.org/ important evolutionary role by buffering destabilizing mutations in its client proteins(111).…”