Universal distribution of protein evolution rates as a consequence of protein folding physics.
The hypothesis that folding robustness is the primary determinant of the evolution rate of proteins is explored using a coarse-grained off-lattice model. The simplicity of the model allows rapid computation of the folding probability of a sequence to any folded conformation. For each robust folder, the network of sequences that share its native structure is identified. The fitness of a sequence is postulated to be a simple function of the number of misfolded molecules that have to be produced to reach a characteristic protein abundance. After fixation probabilities of mutants are computed under a simple population dynamics model, a Markov chain on the fold network is constructed, and the fold-averaged evolution rate is computed. The distribution of the logarithm of the evolution rates across distinct networks exhibits a peak with a long tail on the low rate side and resembles the universal empirical distribution of the evolutionary rates more closely than either distribution resembles the log-normal distribution. The results suggest that the universal distribution of the evolutionary rates of protein-coding genes is a direct consequence of the basic physics of protein folding.
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Alexander E
AE
Lobkovsky
Yuri I
YI
Wolf
Eugene V
EV
Koonin
D001703:Biophysics; D019143:Evolution, Molecular; D008390:Markov Chains; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D011506:Proteins / Q000235:genetics*
D011506:Proteins