Evolution of domain architectures and catalytic functions of enzymes in metabolic systems

Abstract. Domain architectures and catalytic functions of enzymes constitute the centerpieces of a metabolic network. These types of information are formulated as a two-layered network consisting of domains, proteins and reactions – a domain-protein-reaction network. We propose an algorithm to reconstruct the evolutionary history of domain-protein-reaction networks across multiple species and categorize the mechanisms of metabolic systems evolution in terms of network changes. The reconstructed history reveals distinct patterns of evolutionary mechanisms between prokaryotic and eukaryotic networks. While the evolutionary mechanisms in early ancestors of prokaryotes and eukaryotes are quite similar, more novel and duplicated domain compositions with identical catalytic functions arise along the eukaryotic lineage. In contrast, prokaryotic enzymes become more versatile by catalyzing multiple reactions with similar chemical operations. Moreover, different metabolic pathways are enriched with distinct network evolution mechanisms. For instance, while the pathways of steroid biosynthesis, protein kinases and glycosaminoglycan biosynthesis all constitute prominent features of animal-specific physiology, their evolution of domain architectures and catalytic functions follows distinct patterns. Steroid biosynthesis is enriched with reaction creations but retains a relatively conserved repertoire of domain compositions and proteins. Protein kinases retain conserved reactions bu