Selection for Protein Kinetic Stability Connects Denaturation Temperatures to Organismal Temperatures and Provides Clues to Archaean Life

The relationship between the denaturation temperatures of proteins (T m values) and the living temperatures of their host organisms (environmental temperatures: T ENV values) is poorly understood. Since different proteins in the same organism may show widely different T m ’s, no simple universal relationship between T m and T ENV should hold, other than T m ≥T ENV . Yet, when analyzing a set of homologous proteins from different hosts, T m ’s are oftentimes found to correlate with T ENV ’s but this correlation is shifted upward on the T m axis. Supporting this trend, we recently reported T m ’s for resurrected Precambrian thioredoxins that mirror a proposed environmental cooling over long geological time, while remaining a shocking ~50°C above the proposed ancestral ocean temperatures. Here, we show that natural selection for protein kinetic stability (denaturation rate) can produce a T m ↔T ENV correlation with a large upward shift in T m . A model for protein stability evolution suggests a link between the T m shift and the in vivo lifetime of a protein and, more specifically, allows us to estimate ancestral environmental temperatures from experimental denaturation rates for resurrected Precambrian thioredoxins. The T ENV values thus obtained match the proposed ancestral ocean cooling, support comparatively high Archaean temperatures, and are consistent with a recent proposal for the environmental temperature (above 75°C) that hosted the last universal common ancestor. More generally, this work provides a framework for understanding how features of protein stability reflect the environmental temperatures of the host organisms.