A Thermodynamic Atlas of Proteomes Reveals Energetic Innovation across the Tree of Life

Abstract

Protein stability is a fundamental molecular property enabling organisms to adapt to their biological niches. How this is facilitated and whether there are kingdom specific or more general universal strategies is not known. A principal obstacle to addressing this issue is that the vast majority of proteins lack annotation, specifically thermodynamic annotation, beyond the amino acid and chromosome information derived from genome sequencing. To address this gap and facilitate future investigation into large-scale patterns of protein stability and dynamics within and between organisms, we applied a unique ensemble-based thermodynamic characterization of protein folds to a substantial portion of extant sequenced genomes. Using this approach, we compiled a database resource focused on the position-specific variation in protein stability. Interrogation of the database reveals; 1) domains of life exhibit distinguishing thermodynamic features, with eukaryotes particularly different from both archaea and bacteria, 2) the optimal growth temperature of an organism is proportional to the average apolar enthalpy of its proteome, 3) intrinsic disorder content is also proportional to the apolar enthalpy (but unexpectedly not the predicted stability at 25 °C), and 4) secondary structure and global stability information of individual proteins is extractable. We hypothesize that wider access to residue-specific thermodynamic information of proteomes will result in deeper understanding of mechanisms driving functional adaptation and protein evolution. Our database is free for download at https://afc-science.github.io/thermo-env-atlas/.

Heat tolerance, oxidative stress response tuning, and robust gene activation in early-stageDrosophila melanogasterembryos

“…There is evidence supporting this possibility in the form of the evolution of thermal stability of proteins (Dong et al, 2018; Fields and Somero, 1998; Gu and Hilser, 2009), which may influence the temperature at which the cellular stress response is induced (Tomanek and Somero, 2000). But the process of protein evolution depends on the relatively slow accumulation of amino-acid-changing mutations (Chin et al, 2022), such that adaptive divergence across the proteome likely occurs after speciation events. Thus, the short-term evolutionary timescales that separate divergent populations within a species may be too short to render this as a plausible explanation for the data we report on herein.…”