Distribuição universal de taxas de evolução de proteínas como uma consequência de física do dobramento de proteínas

terça-feira, janeiro 26, 2010

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

Alexander E. Lobkovsky, Yuri I. Wolf, and Eugene V. Koonin1

-Author Affiliations

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894

Abstract

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.

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

Footnotes

1To whom correspondence should be addressed. E-mail:koonin@ncbi.nlm.nih.gov.

Edited* by William A. Eaton, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, and approved December 24, 2009 (received for review September 14, 2009)

Author contributions: A.E.L., Y.I.W., and E.V.K. designed research; A.E.L. performed research; A.E.L., Y.I.W., and E.V.K. analyzed data; and A.E.L. and E.V.K. wrote the paper.

↵*This Direct Submission article had a prearranged editor.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0910445107/DCSupplemental.

FREE PDF GRÁTIS [OPEN ACCESS]