Molecular chaperones are highly conserved and ubiquitous proteins that help other
proteins in the cell to fold. Pioneering work by Rutherford and Lindquist suggested that
the chaperone Hsp90 could buffer (i.e., suppress) phenotypic variation in its client
proteins and that alternate periods of buffering and expression of these variants might be
important in adaptive evolution. More recently, Tokuriki and Tawfik presented an explicit
mechanism for chaperone-dependent evolution, in which the Escherichia
coli chaperonin GroEL facilitated the folding of clients that had accumulated
structurally destabilizing but neofunctionalizing mutations in the protein core. But how
important an evolutionary force is chaperonin-mediated buffering in nature? Here, we
address this question by modeling the per-residue evolutionary rate of the crystallized
E. coli proteome, evaluating the relative contributions of chaperonin
buffering, functional importance, and structural features such as residue contact density.
Previous findings suggest an interaction between codon bias and GroEL in limiting the
effects of misfolding errors. Our results suggest that the buffering of deleterious
mutations by GroEL increases the evolutionary rate of client proteins. We then examine the
evolutionary fate of GroEL clients in the Mycoplasmas, a group of
bacteria containing the only known organisms that lack chaperonins. We show that GroEL was
lost once in the common ancestor of a monophyletic subgroup of
Mycoplasmas, and we evaluate the effect of this loss on the subsequent
evolution of client proteins, providing evidence that client homologs in 11
Mycoplasma species have lost their obligate dependency on GroEL for
folding. Our analyses indicate that individual molecules such as chaperonins can have
significant effects on proteome evolution through their modulation of protein folding
