title: Recent assembly of an imprinted domain from non-imprinted components.
abstract: Genomic imprinting, representing parent-specific expression of alleles at a locus, raises many questions about how--and especially why--epigenetic silencing of mammalian genes evolved. We present the first in-depth study of how a human imprinted domain evolved, analyzing a domain containing several imprinted genes that are involved in human disease. Using comparisons of orthologous genes in humans, marsupials, and the platypus, we discovered that the Prader-Willi/Angelman syndrome region on human Chromosome 15q was assembled only recently (105-180 million years ago). This imprinted domain arose after a region bearing UBE3A (Angelman syndrome) fused with an unlinked region bearing SNRPN (Prader-Willi syndrome), which had duplicated from the non-imprinted SNRPB/B'. This region independently acquired several retroposed gene copies and arrays of small nucleolar RNAs from different parts of the genome. In their original configurations, SNRPN and UBE3A are expressed from both alleles, implying that acquisition of imprinting occurred after their rearrangement and required the evolution of a control locus. Thus, the evolution of imprinting in viviparous mammals is ongoing.
authors.affiliation: Australian Research Council Center for Kangaroo Genomics and Research School of Biological Sciences, Australian National University, Canberra, Australia.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Rapkins
authors.forename: Tim
authors.initials: T
authors.lastname: Hore
authors.forename: Megan
authors.initials: M
authors.lastname: Smithwick
authors.forename: Eleanor
authors.initials: E
authors.lastname: Ager
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pask
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Renfree
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohn
authors.forename: Horst
authors.initials: H
authors.lastname: Hameister
authors.forename: Robert D
authors.initials: RD
authors.lastname: Nicholls
authors.forename: Janine E
authors.initials: JE
authors.lastname: Deakin
authors.forename: Jennifer A Marshall
authors.initials: JA
authors.lastname: Graves
mesh_terms: D000483:Alleles; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008394:Marsupialia / Q000235:genetics*; D051379:Mice; D010987:Platypus / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; C526407:SNRPB protein, human; C526417:SNRPN protein, human; C526416:Snrpb protein, mouse; D055517:snRNP Core Proteins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases