The evolution of the metabolic network over long timelines

Metabolism is executed by an efficient, interconnected and ancient biochemical system, the metabolic network. Its evolutionary origins are, however, barely understood. We here discuss that because of niche adaptation, the evolutionary selection acting on the metabolic network structure distinguishes modern species and early life forms. Yet, its basic structure remained conserved over more than three billion years of diverging evolution. We speculate that this situation attributes key roles in metabolic network evolution to (i) the reaction properties of central metabolites, (ii) simple catalysts (e.g. metal ions, amino acids) whose importance remained unchanged during evolution, and (iii) the interconnectivity of the network that limits its expansion. The conservation of network structure hence implies that early life forms already used similar metabolic reaction topologies as modern species.