The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology.
The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5' LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology.
Mallet
François
F
Unité Mixte de Recherche 2142, Centre National de la Recherche Scientifique-bioMérieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. francois.mallet@ens-lyon.fr
Bouton
Olivier
O
Prudhomme
Sarah
S
Cheynet
Valérie
V
Oriol
Guy
G
Bonnaud
Bertrand
B
Lucotte
Gérard
G
Duret
Laurent
L
Mandrand
Bernard
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D005814:Genes, Viral; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010920:Placenta / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D014764:Viral Proteins