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Complex genomic rearrangements lead to novel primate gene function

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Official URL:https://doi.org/10.1101/gr.3266405
PubMed:View item in PubMed
Creators Name:Ciccarelli, F.D. and von Mering, C. and Suyama, M. and Harrington, E.D. and Izaurralde, E. and Bork, P.
Journal Title:Genome Research
Journal Abbreviation:Genome Res
Volume:15
Number:3
Page Range:343-351
Date:1 January 2005
Keywords:Alternative Splicing, Base Sequence, Complementary DNA, Gene Duplication, Gene Rearrangement, Genome, Hela Cells, Human Genome, Humans, Molecular Chaperones, Molecular Evolution, Multigene Family, Nuclear Pore Complex Proteins, Phylogeny, Selection, Animals, Primates
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 ∼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.
ISSN:1088-9051
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Item Type:Article

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