An inter-species protein-protein interaction network across vast evolutionary distance

Area of Science:

• * Molecular and Cellular Biology
• * Evolutionary Biology
• * Systems Biology

Background:

• * Biophysical interactions among macromolecules form complex functional networks within cells.
• * Key questions remain regarding the coordination of biophysical and functional networks, the extent of their overlap, and evolutionary shaping.
• * Understanding these relationships is crucial for deciphering cellular organization and evolution.

Purpose of the Study:

• * To investigate the coordination between biophysical and functional protein interaction networks across species.
• * To determine if biophysical interactions universally map to functional interactions.
• * To explore the evolutionary forces shaping biophysical-versus-functional network coordination.

Main Methods:

• * Employed an "inter-interactome" approach to systematically probe interactions between yeast and human proteomes.
• * Characterized the functional properties of the resulting cross-species biophysical network.
• * Analyzed the degree of functional overlap within the inter-interactome network.

Main Results:

• * Yeast and human proteomes form conserved biophysical networks with properties similar to intra-species networks, even after a billion years of divergence.
• * Significant, though reduced, functional overlap was observed in the yeast-human inter-interactome network, indicating preserved co-functionality beyond direct homologs.
• * Evidence suggests evolutionary selection acts against biophysical interactions lacking co-functionality.

Conclusions:

• * Biophysical protein interaction networks exhibit remarkable evolutionary conservation across distantly related species.
• * Functional co-functionality is preserved in cross-species interactomes, highlighting deep evolutionary roots.
• * Non-functional biophysical interactions may serve as a source for the emergence of new functional interactions over evolutionary time.