title: Complex genomic rearrangements lead to novel primate gene function.
abstract: Orthologous genes that maintain a single-copy status in a broad range of species may indicate a selection against gene duplication. If this is the case, then duplicates of such genes that do survive may have escaped the dosage control by rapid and sizable changes in their function. To test this hypothesis and to develop a strategy for the identification of novel gene functions, we have analyzed 22 primate-specific intrachromosomal duplications of genes with a single-copy ortholog in all other completely sequenced metazoans. When comparing this set to genes not exposed to the single-copy status constraint, we observed a higher tendency of the former to modify their gene structure, often through complex genomic rearrangements. The analysis of the most dramatic of these duplications, affecting approximately 10% of human Chromosome 2, enabled a detailed reconstruction of the events leading to the appearance of a novel gene family. The eight members of this family originated from the highly conserved nucleoporin RanBP2 by several genetic rearrangements such as segmental duplications, inversions, translocations, exon loss, and domain accretion. We have experimentally verified that at least one of the newly formed proteins has a cellular localization different from RanBP2's, and we show that positive selection did act on specific domains during evolution.
authors.affiliation: European Molecular Biology Laboratory, 69012 Heidelberg, Germany.
authors.forename: Francesca D
authors.initials: FD
authors.lastname: Ciccarelli
authors.forename: Christian
authors.initials: C
authors.lastname: von Mering
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.forename: Eoghan D
authors.initials: ED
authors.lastname: Harrington
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D020440:Gene Duplication; D015321:Gene Rearrangement; D016678:Genome; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D005810:Multigene Family; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D018076:DNA, Complementary; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2