RT Journal Article
SR Electronic
T1 Avoidance of toxic misfolding does not explain the sequence constrains of highly expressed proteins across organisms
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 168963
DO 10.1101/168963
A1 Germán Plata
A1 Dennis Vitkup
YR 2017
UL http://biorxiv.org/content/early/2017/07/27/168963.abstract
AB The avoidance of cytotoxic effects associated with protein misfolding has been proposed as a dominant constraint for the evolution of highly expressed proteins. Recently, Leuenberger et al. developed an elegant experimental approach to measure protein thermal stability at the proteome scale. The collected data allow to rigorously test key predictions of the misfolding avoidance hypothesis. Specifically, that highly expressed proteins are designed to be more stable, and that thermodynamic stability significantly constrains their evolution. Careful re-analyses of the Leuenberger et al. data across four different organisms show no substantial correlation between protein stability and protein abundance. We also find that protein stability does not substantially contribute to sequence constraints of highly abundant proteins. Therefore, the key prediction of the misfolding toxicity avoidance hypothesis is not supported by the empirical data.