Universal distribution of protein evolution rates as a consequence of protein folding physics

作者：Lobkovsky Alexander E; Wolf Yuri I; Koonin Eugene V^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(7): 2983-2988.

DOI：10.1073/pnas.0910445107

• correct folding probability
• evolutionary rate distribution
• off-lattice models
• common structure networks
• network average evolution rate

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.

• 出版日期2010-2-16