Protein domains are compact evolutionary units of structure and function that 
usually combine in proteins to produce complex domain arrangements. In order to 
study their evolution, we reconstructed genome-based phylogenetic trees of 
architectures from a census of domain structure and organization conducted at 
protein fold and fold-superfamily levels in hundreds of fully sequenced genomes. 
These trees defined timelines of architectural discovery and revealed remarkable 
evolutionary patterns, including the explosive appearance of domain combinations 
during the rise of organismal lineages, the dominance of domain fusion processes 
throughout evolution, and the late appearance of a new class of multifunctional 
modules in Eukarya by fission of domain combinations. Our study provides a 
detailed account of the history and diversification of a molecular interactome 
and shows how the interplay of domain fusions and fissions defines an 
evolutionary mechanics of domain organization that is fundamentally responsible 
for the complexity of the protein world.