Chaperonin-Dependent Accelerated Substitution Rates in Prokaryotes

Abstract

Many proteins require the assistance of molecular chaperones in order to fold efficiently. Chaperones are known to mask the effects of mutations that induce misfolding because they can compensate for the deficiency in spontaneous folding. One of the best studied chaperones is the eubacterial GroEL/GroES system. In Escherichia coli, three classes of proteins have been distinguished based on their degree of dependency on GroEL for folding: 1) those that do not require GroEL, 2) those that require GroEL in a temperature-dependent manner, and 3) those that obligately require GroEL for proper folding. The buffering effects of GroEL have so far been observed in experimental regimens, but their effect on genomes during evolution has not been examined. Using 446 sequenced proteobacterial genomes, we have compared the frequency of amino acid replacements among orthologs of 236 proteins corresponding to the three categories of GroEL dependency determined for E. coli. Evolutionary rates are significantly correlated with GroEL dependency upon folding with GroEL dependency class accounting for up to 84% of the variation in amino acid substitution rates. Greater GroEL dependency entails increased evolutionary rates with GroEL obligatory proteins (Class III) evolving on average up to 15% faster than GroEL partially dependent proteins (Class II) and 35% faster than GroEL-independent proteins (Class I). Moreover, GroEL dependency class correlations are strictly conserved throughout all proteobacteria surveyed, as is a significant correlation between folding class and codon bias. The results suggest that during evolution, GroEL-dependent folding increases evolutionary rate by buffering the deleterious effects of misfolding-related mutations.

Evolution of Chaperonin Gene Duplication in Stigonematalean Cyanobacteria (Subsection V)

“…GroESL-mediated folding has been shown to accelerate protein evolution in vitro (Tokuriki and Tawfik 2009). This phenomenon is evident in genomic comparisons of eubacterial organisms as obligatory GroEL substrates were found to evolve faster than casual GroEL interactors (Bogumil and Dagan 2010; Warnecke and Hurst 2010; Williams and Fares 2010). …”

Survival and innovation: The role of mutational robustness in evolution

“…A prediction derived from these studies is that protein clients requiring GroEL for folding should be candidates for accelerated evolution more readily so than proteins those do not require GroEL. Indeed, GroEL clients have been shown to evolve at a faster rate than nonclient proteins (e.g., they fix more amino acid replacing mutations), once gene essentiality, proteineprotein interaction degree and expression levelsdknown factors to influence the rates of evolution [57]dhave been controlled for [58,59].…”

Protein folding in the cell: challenges and progress

“…A key challenge is how an organism copes with ‘weak-link’ protein variants as it moves towards more successfully evolved versions. One strategy exploits chaperones as buffers, enabling the organism to cope with mutated proteins that have impaired folding properties [81,83,84]. In a recent study, Shamoo and coworkers explicitly designed a weak-link challenge and asked how it was overcome: They substituted the normal (and essential) gene for adenylate kinase in the thermophile Geobacillus stearothermophilus by the analogous gene from the mesophile B. subtilis and grew the resulting bacterial population at high temperatures to force competition between mutants [85,86].…”