title: Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes.
abstract: BACKGROUND
  The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs), which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role.
  
  
  RESULTS
  To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs]) for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show--using an ex vivo fusion assay for each allelic form--that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most--but not all--of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including envW and envFRD.
  
  
  CONCLUSIONS
  Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved.
authors.affiliation: UMR 8122 CNRS, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. parseval@igr.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: de Parseval
authors.forename: Gora
authors.initials: G
authors.lastname: Diop
authors.forename: Sandra
authors.initials: S
authors.lastname: Blaise
authors.forename: François
authors.initials: F
authors.lastname: Helle
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vasilescu
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Thierry
authors.initials: T
authors.lastname: Heidmann
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D019143:Evolution, Molecular; D014644:Genetic Variation; D005822:Genetic Vectors; D016678:Genome; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D016366:Open Reading Frames; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011323:Primates; D011544:Pseudogenes; D012190:Retroviridae / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D004247:DNA