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 similar to 50 degrees 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 degrees 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.