title: Captured retroviral envelope syncytin gene associated with the unique placental structure of higher ruminants.
abstract: Syncytins are envelope genes of retroviral origin that have been co-opted for a role in placentation and likely contribute to the remarkable diversity of placental structures. Independent capture events have been identified in primates, rodents, lagomorphs, and carnivores, where they are involved in the formation of a syncytium layer at the fetomaternal interface via trophoblast cell-cell fusion. We searched for similar genes within the suborder Ruminantia where the placenta lacks an extended syncytium layer but displays a heterologous cell-fusion process unique among eutherian mammals. An in silico search for intact envelope genes within the Bos taurus genome identified 18 candidates belonging to five endogenous retrovirus families, with one gene displaying both placenta-specific expression, as assessed by quantitative RT-PCR analyses of a large panel of tissues, and conservation in the Ovis aries genome. Both the bovine and ovine orthologs displayed fusogenic activity by conferring infectivity on retroviral pseudotypes and triggering cell-cell fusion. In situ hybridization of placenta sections revealed specific expression in the trophoblast binucleate cells, consistent with a role in the formation--by heterologous cell fusion with uterine cells--of the trinucleate cells of the cow and the syncytial plaques of the ewe. Finally, we show that this gene, which we named "Syncytin-Rum1," is conserved among 16 representatives of higher ruminants, with evidence for purifying selection and conservation of its fusogenic properties, over 30 millions years of evolution. These data argue for syncytins being a major driving force in the emergence and diversity of the placenta.
authors: Unité Mixte de Recherche 8122, Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, France.
authors: Guillaume
authors: G
authors: Cornelis
authors: Odile
authors: O
authors: Heidmann
authors: Séverine A
authors: SA
authors: Degrelle
authors: Cécile
authors: C
authors: Vernochet
authors: Christian
authors: C
authors: Lavialle
authors: Claire
authors: C
authors: Letzelter
authors: Sibylle
authors: S
authors: Bernard-Stoecklin
authors: Alexandre
authors: A
authors: Hassanin
authors: Baptiste
authors: B
authors: Mulot
authors: Michel
authors: M
authors: Guillomot
authors: Isabelle
authors: I
authors: Hue
authors: Thierry
authors: T
authors: Heidmann
authors: Anne
authors: A
authors: Dupressoir
mesh_terms: D000818:Animals; D002417:Cattle; D019295:Computational Biology; D017124:Conserved Sequence; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000235:genetics*; D056726:Genetic Association Studies; D014644:Genetic Variation; D016678:Genome / Q000235:genetics; D006041:Goats / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D010802:Phylogeny; D010920:Placenta / Q000033:anatomy & histology* / Q000166:cytology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012418:Ruminants / Q000235:genetics*; D012641:Selection, Genetic; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D014759:Viral Envelope Proteins; C405335:syncytin
references: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3782-7
references: 20142478
references: J Virol. 1994 Mar;68(3):1773-81
references: 8107239
references: J Morphol. 2006 Jan;267(1):50-6
references: 16240388
references: J Virol. 2001 Dec;75(23):11319-27
references: 11689612
references: Placenta. 2012 Sep;33(9):663-71
references: 22695103
references: PLoS One. 2011 Apr 19;6(4):e18630
references: 21526184
references: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12127-32
references: 19564597
references: Mol Cell Biol. 2000 Apr;20(7):2466-74
references: 10713170
references: Genetics. 2000 May;155(1):431-49
references: 10790415
references: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14390-5
references: 16980413
references: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1164-73
references: 22032925
references: Reprod Biol Endocrinol. 2012 May 25;10:41
references: 22632112
references: Bioinformatics. 2006 Nov 1;22(21):2688-90
references: 16928733
references: Nat Genet. 2000 Jul;25(3):311-4
references: 10888880
references: Development. 2008 Jun;135(12):2083-91
references: 18448564
references: Virology. 1984 Mar;133(2):393-402
references: 6324459
references: J Virol. 2000 Apr;74(7):3321-9
references: 10708449
references: J Biol Chem. 2002 Dec 20;277(51):50062-8
references: 12397062
references: Microsc Res Tech. 1997 Jul 1-15;38(1-2):88-99
references: 9260840
references: Exp Clin Endocrinol. 1994;102(3):122-34
references: 7995333
references: Annu Rev Genet. 2008;42:709-32
references: 18694346
references: Theriogenology. 1988;29(3):693-714
references: 16726390
references: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):E432-41
references: 22308384
references: Retrovirology. 2009 Nov 27;6:107
references: 19943933
references: Nature. 2000 Feb 17;403(6771):785-9
references: 10693809
references: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):725-30
references: 15644441
references: J Virol. 2009 Nov;83(22):11447-55
references: 19726505
references: Reprod Biol Endocrinol. 2004 Jul 05;2:46
references: 15236656
references: Placenta. 2007 Feb-Mar;28(2-3):185-91
references: 16714059
references: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20534-9
references: 18077339
references: Mol Biol Evol. 2007 Aug;24(8):1586-91
references: 17483113
references: Mol Biol Evol. 2005 May;22(5):1208-22
references: 15703242
references: C R Biol. 2012 Jan;335(1):32-50
references: 22226162
references: Placenta. 2007 Oct;28(10):1039-48
references: 17597203
references: Virus Genes. 2003 May;26(3):291-315
references: 12876457
references: Am J Anat. 1984 Jun;170(2):233-50
references: 6465051
references: J Virol. 2011 Feb;85(3):1237-45
references: 21084469
references: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13013-8
references: 14557543
references: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18644-9
references: 19846765
references: Science. 2011 Oct 28;334(6055):521-4
references: 21940861
references: Placenta. 1992 Mar-Apr;13(2):101-13
references: 1631024
references: J Virol. 2004 Jan;78(2):1050-4
references: 14694139
references: Am J Anat. 1980 Nov;159(3):285-306
references: 7211711
references: Placenta. 1983;4 Spec No:527-39
references: 6672813
references: J Reprod Dev. 2012;58(1):33-7
references: 22450282