How do individual subunits of conserved molecular complexes acquire novel functions?

Abstract

Molecular machines composed of multiple subunits orchestrate essential cellular processes. Most of them were already present in the last eukaryotic ancestor. Therefore, understanding how these complexes evolve and specialize is crucial to comprehend the emergence and evolution of modern cellular complexity. However, our current understanding of the molecular mechanisms that underlie functional diversification of multimeric proteins remains limited. Here, we used the plant exocyst complex as a model to study the evolution and mechanistic basis of neo-functionalization in protein complexes. We leveraged a combination of cell biology, proteomics, biochemistry, genetics, and phylogenetic analysis to show how changes in a single exocyst subunit, Exo70, altered its association with the rest of the subunits and allowed Exo70 proteins to rapidly diversify and acquire novel functions in plants. Our findings demonstrate how a single subunit escapes from the evolutionary constrains of its ancestral multimeric complex, resulting in neofunctionalization and emergence of increased cellular complexity.