Protein evolution speed depends on its stability and abundance and on chaperone concentrations

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 37; pp. 9092 - 9097
• Main Authors: Agozzino, Luca, Dill, Ken A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11-09-2018
• Subjects: Biological Sciences; Biological variation; Capacitance; Chaperones; Evolution; Fitness; Heating; Hydrophobic surfaces; Hydrophobicity; Landscape; Physical Sciences; Protein folding; Proteins; Rate theory; Reproductive fitness; Stability; protein evolution; adaptation; substitution rate
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1810194115

Proteins evolve at different rates. What drives the speed of protein sequence changes? Two main factors are a protein’s folding stability and aggregation propensity. By combining the hydrophobic–polar (HP) model with the Zwanzig–Szabo–Bagchi rate theory, we find that: (i) Adaptation is strongly accelerated by selection pressure, explaining the broad variation from days to thousands of years over which organisms adapt to new environments. (ii) The proteins that adapt fastest are those that are not very stably folded, because their fitness landscapes are steepest. And because heating destabilizes folded proteins, we predict that cells should adapt faster when put into warmer rather than cooler environments. (iii) Increasing protein abundance slows down evolution (the substitution rate of the sequence) because a typical protein is not perfectly fit, so increasing its number of copies reduces the cell’s fitness. (iv) However, chaperones can mitigate this abundance effect and accelerate evolution (also called evolutionary capacitance) by effectively enhancing protein stability. This model explains key observations about protein evolution rates.