Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding
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AuthorGámiz Arco, María Gloria; Risso, Valeria Alejandra; Candel, Adela M.; Inglés Prieto, Álvaro; Romero Romero, María Luisa; Gaucher, Eric A.; Gavira Gallardo, José Antonio; Ibarra Molero, Beatriz; Sánchez Ruiz, José Manuel
Gamiz-Arco, G., Risso, V. A., Candel, A. M., Inglés-Prieto, A., Romero-Romero, M. L., Gaucher, E. A., ... & Sanchez-Ruiz, J. M. (2019). Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding. Biochemical Journal, 476(23), 3631-3647.
SponsorshipThis research was supported by FEDER Funds, grant BIO2015-66426-R from the Spanish Ministry of Economy and Competitiveness ( J.M.S.-R.), grant RGP0041/2017 from the Human Frontier Science Program ( J.M.S.-R. and E.A.G.) and National Institutes of Health 1R01AR069137 (E.A.G.), Department of Defence MURI W911NF-16-1-0372 (E.A.G.).
Evolution involves not only adaptation, but also the degradation of superfluous features. Many examples of degradation at the morphological level are known (vestigial organs, for instance). However, the impact of degradation on molecular evolution has been rarely addressed. Thioredoxins serve as general oxidoreductases in all cells. Here, we report extensive mutational analyses on the folding of modern and resurrected ancestral bacterial thioredoxins. Contrary to claims from recent literature, in vitro folding rates in the thioredoxin family are not evolutionarily conserved, but span at least a ∼100-fold range. Furthermore, modern thioredoxin folding is often substantially slower than ancestral thioredoxin folding. Unassisted folding, as probed in vitro, thus emerges as an ancestral vestigial feature that underwent degradation, plausibly upon the evolutionary emergence of efficient cellular folding assistance. More generally, our results provide evidence that degradation of ancestral features shapes, not only morphological evolution, but also the evolution of individual proteins.