DnaK-Dependent Accelerated Evolutionary Rate in Prokaryotes.

Many proteins depend on an interaction with molecular chaperones in order to fold into a functional tertiary structure. Previous studies showed that protein interaction with the GroEUGroES chaperonine and Hsp90 chaperone can buffer the impact of slightly deleterious mutations in the protein sequence. This capacity of GroEUGroES to prevent protein misfolding has been shown to accelerate the evolution of its client proteins. Whether other bacterial chaperones have a similar effect on their client proteins is currently unknown. Here, we study the impact of DnaK (Hsp70) chaperone on the evolution of its client proteins. Evolutionary parameters were derived from comparison of the Escherichia coil proteome to 1,808,565 orthologous proteins in 1,149 proteobacterial genomes. Our analysis reveals a significant positive correlation between protein binding frequency with DnaK and evolutionary rate. Proteins with high binding affinity to DnaK evolve on average 4.3 -fold faster than proteins in the lowest binding affinity class at the genus resolution. Differences in evolutionary rates of DnaK interactor classes are still significant after adjusting for possible effects caused by protein expression level. Furthermore, we observe an additive effect of DnaK and GroFL chaperones on the evolutionary rates of their common interactors. Finally, we found pronounced similarities in the physicochemical profiles that characterize proteins belonging to DnaK and GroFL interactomes. Our results thus implicate DnaK-mediated folding as a major component in shaping protein evolutionary dynamics in bacteria and supply further evidence for the long-term manifestation of chaperone mediated folding on genome evolution.