title: Evolutionary history and functional implications of protein domains and their combinations in eukaryotes.
abstract: BACKGROUND
  In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes.
  
  
  RESULTS
  We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors.
  
  
  CONCLUSIONS
  Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Itoh
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nacher
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Kuma
authors.forename: Susumu
authors.initials: S
authors.lastname: Goto
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanehisa
mesh_terms: D000818:Animals; D005057:Eukaryotic Cells / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D020543:Proteome
chemical_list: D011506:Proteins; D020543:Proteome