Understanding hierarchical protein evolution from first principles

TL;DR

This paper introduces a model explaining the hierarchical organization of proteins in fold families based on native state stability, revealing how different evolutionary time scales influence protein conservation and structure.

Contribution

The paper presents a novel model linking protein stability to hierarchical evolution, with analytical solutions matching observed amino acid conservation patterns.

Findings

Reproduces amino acid conservation patterns across protein families

Identifies separation of evolutionary time scales in protein evolution

Provides a profile solution aligning with natural amino acid patterns

Abstract

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved across protein families. Due to its dynamic nature, the model sheds light on the evolutionary time scales. By studying the relaxation of the correlation function between consecutive mutations at a given position in proteins, we observe separation of the evolutionary time scales: at the short time intervals families of proteins with similar sequences and structures are formed, while at long time intervals the families of structurally similar proteins that have low sequence similarity are formed. We discuss the evolutionary implications of our model. We provide a ``profile'' solution to our model and find agreement between predicted patterns of conserved amino acids and those actually observed in nature.