Abstract
The consistent observation across all kingdoms of life that highly abundant proteins evolve slowly demonstrates that cellular abundance is a key determinant of protein evolutionary rate. However, other empirical findings, such as the broad distribution of evolutionary rates, suggest that additional variables determine the rate of protein evolution. Here, we report that under the global selection against the cytotoxic effects of misfolded proteins, folding stability (Δ. G), simultaneous with abundance, is a causal variable of evolutionary rate. Using both theoretical analysis and multiscale simulations, we demonstrate that the anticorrelation between the premutation Δ. G and the arising mutational effect (ΔΔ. G), purely biophysical in origin, is a necessary requirement for abundance-evolutionary rate covariation. Additionally, we predict and demonstrate in bacteria that the strength of abundance-evolutionary rate correlation depends on the divergence time separating reference genomes. Altogether, these results highlight the intrinsic role of protein biophysics in the emerging universal patterns of molecular evolution.
| Original language | English |
|---|---|
| Pages (from-to) | 242-248 |
| Number of pages | 7 |
| Journal | Cell Reports |
| Volume | 2 |
| Issue number | 2 |
| DOIs | |
| State | Published - 30 Aug 2012 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank N. King and M.J. Westbrook (University of California, Berkeley), L.Z. Holland (University of California, San Diego), P.A.V. Anderson (University of Florida), and B. Schierwater and M. Eitel (Institut für Tierökologie und Zellbiologie, Hannover) for providing RNA and tissue samples; D. Fredman (University of Vienna) for sharing data; and T.J. Jegla (Penn State University) and N. Dascal (Tel Aviv University) for critical comments. Y.M. was supported by an EMBO long-term fellowship (ALTF 1096-2009). A.M.R. was supported by award F32HD062178 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. This study was supported by a research grant from the Austrian National Science Foundation (FWF P 21108-B17) to U.T., and by a United States-Israel Binational Agricultural Research and Development Grant (IS-4313-10) and an Israeli Science Foundation grant (107/08) to M.G.