title: Quantifying the mechanisms of domain gain in animal proteins.
abstract: BACKGROUND
  Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms.
  
  
  RESULTS
  Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events.
  
  
  CONCLUSIONS
  The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. mb613@cam.ac.uk
authors.forename: Marija
authors.initials: M
authors.lastname: Buljan
authors.forename: Adam
authors.initials: A
authors.lastname: Frankish
authors.forename: Alex
authors.initials: A
authors.lastname: Bateman
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D020440:Gene Duplication / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013997:Time Factors
chemical_list: D000596:Amino Acids; D011506:Proteins; D012333:RNA, Messenger