RT Journal Article
SR Electronic
T1 Higher temperatures worsen the effects of mutations on protein stability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.13.337972
DO 10.1101/2020.10.13.337972
A1 Kontopoulos, Dimitrios - Georgios
A1 Patmanidis, Ilias
A1 Barraclough, Timothy G.
A1 Pawar, Samraat
YR 2020
UL http://biorxiv.org/content/early/2020/10/14/2020.10.13.337972.abstract
AB Understanding whether and how temperature increases alter the effects of mutations on protein stability is crucial for understanding the limits to thermal adaptation by organisms. Currently, it is generally assumed that the stability effects of mutations are independent of temperature. Yet, mutations should become increasingly destabilizing as temperature rises due to the increase in the energy of atoms. Here, by performing an extensive computational analysis on the essential enzyme adenylate kinase in prokaryotes, we show, for the first time, that mutations become more destabilizing with temperature both across and within species. Consistent with these findings, we find that substitution rates of prokaryotes decrease nonlinearly with temperature. Our results suggest that life on Earth likely originated in a moderately thermophilic and thermally fluctuating environment, and indicate that global warming should decrease the per-generation rate of molecular evolution of prokaryotes.Competing Interest StatementThe authors have declared no competing interest.