The cumulative impact of chaperone mediated protein- folding during evolution
Molecular chaperones support protein folding and unfolding along with assembly and translocation of protein complexes. Chaperones have been recognized as important mediators between organismal genotype and phenotype as well as important maintainers of cellular fitness under environmental conditions that induce high mutational loads. This thesis presents recent studies revealing that the folding assistance supplied by chaperones is evident in genomic sequences, thus implicating chaperone-mediated folding as an influential factor during protein evolution. Furthermore the evolution and the symbiogenic origin of the eukaryotic chaperone repertoire are elucidated. Protein interaction with chaperones ensures a proper folding and function, yet an adaptation to obligatory dependence on such assistance may be irreversible, representing an evolutionary trap. Correlation between chaperone requirement and protein expression level indicate that the evolution of substrate-chaperone interaction is bounded by the required substrate abundance within the cell. Accumulating evidence suggests that the utility of chaperones is governed by a delicate balance between their help in mitigating the risks of protein misfolding and aggregate formation on the one hand, and the slower rate of protein maturation and the energetic cost of chaperone synthesis on the other.