The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform

Anne Dupressoir - One of the best experts on this subject based on the ideXlab platform.

  • capture of a hyena specific retroviral Envelope Gene with placental expression associated in evolution with the unique emergence among carnivorans of hemochorial placentation in hyaenidae
    Journal of Virology, 2018
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Odile Heidmann, Anne Dupressoir, Mathis Funk
    Abstract:

    ABSTRACT Capture of retroviral Envelope Genes from endogenous retroviruses has played a role in the evolution of mammals, with evidence for the involvement of these Genes in the formation of the maternofetal interface of the placenta. It has been shown that the diversity of captured Genes is likely to be responsible for the diversity of placental structures, ranging from poorly invasive (epitheliochorial) to highly invasive (hemochorial), with an intermediate state (endotheliochorial) as found in carnivorans. The latter recapitulate part of this evolution, with the hyena being the sole carnivoran with a hemochorial placenta. In this study, we performed RNA sequencing on hyena placental transcripts and searched for endogenous retroviral Envelope Genes that have been captured specifically in the Hyaenidae clade and are not found in any other carnivoran. We identified an Envelope Gene that is expressed in the placenta at the level of the maternofetal interface, as evidenced by in situ hybridization/immunohistochemistry. The Gene entry is coincidental with the emergence of the Hyaenidae clade 30 million years ago (Mya), being found at the same genomic locus in all 4 extant hyena species. Its coding sequence has further been maintained during all of Hyaenidae evolution. It is not found in any of the 30 other carnivorans—both Felidae and Canidae—that we screened. This Envelope protein does not disclose any fusogenic activity in ex vivo assays, at variance with the syncytin-Car1 Gene, which is found in all carnivorans, including the hyena, in which it is still present, transcriptionally active in the placenta, and fusogenic. Together, the present results illustrate the permanent renewal of placenta-specific Genes by retroviral capture and de facto provide a candidate Gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. IMPORTANCE The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral Envelope Genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral Envelope Gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared syncytin-Car1 Gene. This new env Gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of Virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud Tennant, Anne Dupressoir
    Abstract:

    Syncytin Genes are fusogenic Envelope protein (env) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by quantitative reverse transcription-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 million years ago, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven Syncytin Genes identified to date in eutherian mammals and is likely to be a major effector of placentation in its related clade. Importance: Syncytin Genes are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a Syncytin: it is specifically expressed in the placenta of the woodchuck Marmota monax, at the level of cells fusing into a syncytium; it can trigger cell-cell and virus-cell fusion ex vivo; and it has been conserved for >25 million years of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other Syncytin Genes identified thus far in mammals (primates, muroids, carnivores, and ruminants). These results extend the range of retroviral Envelope Gene "domestication" in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud C. Tennant, Anne Dupressoir
    Abstract:

    Syncytins are fusogenic Envelope protein ( env ) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by qRT-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 Mya, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven syncytin Genes identified to date in eutherian mammals, and is likely to be a major effector of placentation in its related clade. IMPORTANCE Syncytins are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a syncytin : it is specifically expressed in the placenta of the woodchuck Marmota monax , at the level of cells fusing into a syncytium, it can trigger cell-cell and virus-cell fusion ex vivo , it has been conserved for >25 My of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other syncytins identified so far in mammals (primates, muroids, carnivores and ruminants). These results extend the range of retroviral Envelope Gene ‘domestication’ in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Identification of autonomous IAP LTR retrotransposons mobile in mammalian cells
    Nature Genetics, 2004
    Co-Authors: Marie Dewannieux, Anne Dupressoir, Francis Harper, Gérard Pierron, Thierry Heidmann
    Abstract:

    Mammalian genomes contain two main classes of retrotransposons, the well-characterized long and short interspersed nuclear elements, which account for ∼30% of the genome, and the long terminal repeat (LTR) retrotransposons, which resemble the proviral integrated form of retroviruses, except for the absence of an Envelope Gene in some cases. Genetic studies confirmed mobility of the latter class of elements in mice, with a high proportion of phenotypic mutations consequent to transposition of the intracisternal A particle (IAP) family of LTR retrotransposons^ 1 . Using the mouse genome sequence and an efficient ex vivo retrotransposition assay, we identified functional, master IAP copies that encode all the enzymatic and structural proteins necessary for their autonomous transposition in heterologous cells. By introducing mutations, we found that the three Genes gag , prt and pol are all required for retrotransposition and identified the IAP Gene products by electron microscopy in the form of intracellular A-type particles in the transfected cells. These prototypic elements, devoid of an Envelope Gene, are the first LTR retrotransposons autonomous for transposition to be identified in mammals. Their high rates of retrotransposition indicate that they are potent insertional mutagens that could serve as safe (noninfectious) Genetic tools in a large panel of cells.

  • identification of autonomous iap ltr retrotransposons mobile in mammalian cells
    Nature Genetics, 2004
    Co-Authors: Marie Dewannieux, Anne Dupressoir, Francis Harper, Gérard Pierron, Thierry Heidmann
    Abstract:

    Mammalian genomes contain two main classes of retrotransposons, the well-characterized long and short interspersed nuclear elements, which account for approximately 30% of the genome, and the long terminal repeat (LTR) retrotransposons, which resemble the proviral integrated form of retroviruses, except for the absence of an Envelope Gene in some cases. Genetic studies confirmed mobility of the latter class of elements in mice, with a high proportion of phenotypic mutations consequent to transposition of the intracisternal A particle (IAP) family of LTR retrotransposons. Using the mouse genome sequence and an efficient ex vivo retrotransposition assay, we identified functional, master IAP copies that encode all the enzymatic and structural proteins necessary for their autonomous transposition in heterologous cells. By introducing mutations, we found that the three Genes gag, prt and pol are all required for retrotransposition and identified the IAP Gene products by electron microscopy in the form of intracellular A-type particles in the transfected cells. These prototypic elements, devoid of an Envelope Gene, are the first LTR retrotransposons autonomous for transposition to be identified in mammals. Their high rates of retrotransposition indicate that they are potent insertional mutagens that could serve as safe (noninfectious) Genetic tools in a large panel of cells.

Thierry Heidmann - One of the best experts on this subject based on the ideXlab platform.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of Virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud Tennant, Anne Dupressoir
    Abstract:

    Syncytin Genes are fusogenic Envelope protein (env) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by quantitative reverse transcription-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 million years ago, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven Syncytin Genes identified to date in eutherian mammals and is likely to be a major effector of placentation in its related clade. Importance: Syncytin Genes are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a Syncytin: it is specifically expressed in the placenta of the woodchuck Marmota monax, at the level of cells fusing into a syncytium; it can trigger cell-cell and virus-cell fusion ex vivo; and it has been conserved for >25 million years of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other Syncytin Genes identified thus far in mammals (primates, muroids, carnivores, and ruminants). These results extend the range of retroviral Envelope Gene "domestication" in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud C. Tennant, Anne Dupressoir
    Abstract:

    Syncytins are fusogenic Envelope protein ( env ) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by qRT-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 Mya, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven syncytin Genes identified to date in eutherian mammals, and is likely to be a major effector of placentation in its related clade. IMPORTANCE Syncytins are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a syncytin : it is specifically expressed in the placenta of the woodchuck Marmota monax , at the level of cells fusing into a syncytium, it can trigger cell-cell and virus-cell fusion ex vivo , it has been conserved for >25 My of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other syncytins identified so far in mammals (primates, muroids, carnivores and ruminants). These results extend the range of retroviral Envelope Gene ‘domestication’ in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Differential evolutionary fate of an ancestral primate endogenous retrovirus Envelope Gene, the EnvV syncytin, captured for a function in placentation.
    PLoS genetics, 2013
    Co-Authors: Cécile Esnault, Guillaume Cornelis, Odile Heidmann, Thierry Heidmann
    Abstract:

    Syncytins are Envelope Genes of retroviral origin that have been co-opted for a role in placentation. They promote cell–cell fusion and are involved in the formation of a syncytium layer—the syncytiotrophoblast—at the materno-fetal interface. They were captured independently in eutherian mammals, and knockout mice demonstrated that they are absolutely required for placenta formation and embryo survival. Here we provide evidence that these “necessary” Genes acquired “by chance” have a definite lifetime with diverse fates depending on the animal lineage, being both gained and lost in the course of evolution. Analysis of a retroviral Envelope Gene, the envV Gene, present in primate genomes and belonging to the endogenous retrovirus type V (ERV-V) provirus, shows that this captured Gene, which entered the primate lineage >45 million years ago, behaves as a syncytin in Old World monkeys, but lost its canonical fusogenic activity in other primate lineages, including humans. In the Old World monkeys, we show—by in situ analyses and ex vivo assays—that envV is both specifically expressed at the level of the placental syncytiotrophoblast and fusogenic, and that it further displays signs of purifying selection based on analysis of non-synonymous to synonymous substitution rates. We further show that purifying selection still operates in the primate lineages where the Gene is no longer fusogenic, indicating that deGeneracy of this ancestral syncytin is a slow, lineage-dependent, and multi-step process, in which the fusogenic activity would be the first canonical property of this retroviral Envelope Gene to be lost.

  • crystal structure of a pivotal domain of human syncytin 2 a 40 million years old endogenous retrovirus fusogenic Envelope Gene captured by primates
    Journal of Molecular Biology, 2005
    Co-Authors: Martial Renard, Paloma F Varela, Claire Letzelter, Stephane Duquerroy, Felix A Rey, Thierry Heidmann
    Abstract:

    HERV-FRD is a human endogenous retrovirus that entered the human genome 40 million years ago. Its Envelope Gene, syncytin-2, was diverted by an ancestral host most probably because of its fusogenic property, for a role in placenta morphoGenesis. It was maintained in a functional state in all primate branches as a bona fide cellular Gene, submitted to a very low mutation rate as compared to infectious retrovirus genomes. The structure of the syncytin-2 protein thus provides a good insight into that of the oldest mammalian retroviral Envelope. Here, we report the crystal structure of a central fragment of its “fossil” ectodomain, allowing a remarkable superposition with the structures of the corresponding domains of present-day infectious retroviruses, in spite of a more than 60% divergent sequence. These results suggest the existence of a unique structural solution selected by these proteins for their fusogenic function.

  • Functional characterization of two newly identified Human Endogenous Retrovirus coding Envelope Genes
    Retrovirology, 2005
    Co-Authors: Sandra Blaise, Nathalie De Parseval, Thierry Heidmann
    Abstract:

    A recent in silico search for coding sequences of retroviral origin present in the human genome has unraveled two new Envelope Genes that add to the 16 Genes previously identified. A systematic search among the latter for a fusogenic activity had led to the identification of two bona fide Genes, named syncytin-1 and syncytin-2, most probably co-opted by primate genomes for a placental function related to the formation of the syncytiotrophoblast by cell-cell fusion. Here, we show that one of the newly identified Envelope Gene, named envP(b), is fusogenic in an ex vivo assay, but that its expression – as quantified by real-time RT-PCR on a large panel of human tissues – is ubiquitous, albeit with a rather low value in most tissues. Conversely, the second Envelope Gene, named envV, discloses a placenta-specific expression, but is not fusogenic in any of the cells tested. Altogether, these results suggest that at least one of these env Genes may play a role in placentation, but most probably through a process different from that of the two previously identified syncytins.

Guillaume Cornelis - One of the best experts on this subject based on the ideXlab platform.

  • capture of a hyena specific retroviral Envelope Gene with placental expression associated in evolution with the unique emergence among carnivorans of hemochorial placentation in hyaenidae
    Journal of Virology, 2018
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Odile Heidmann, Anne Dupressoir, Mathis Funk
    Abstract:

    ABSTRACT Capture of retroviral Envelope Genes from endogenous retroviruses has played a role in the evolution of mammals, with evidence for the involvement of these Genes in the formation of the maternofetal interface of the placenta. It has been shown that the diversity of captured Genes is likely to be responsible for the diversity of placental structures, ranging from poorly invasive (epitheliochorial) to highly invasive (hemochorial), with an intermediate state (endotheliochorial) as found in carnivorans. The latter recapitulate part of this evolution, with the hyena being the sole carnivoran with a hemochorial placenta. In this study, we performed RNA sequencing on hyena placental transcripts and searched for endogenous retroviral Envelope Genes that have been captured specifically in the Hyaenidae clade and are not found in any other carnivoran. We identified an Envelope Gene that is expressed in the placenta at the level of the maternofetal interface, as evidenced by in situ hybridization/immunohistochemistry. The Gene entry is coincidental with the emergence of the Hyaenidae clade 30 million years ago (Mya), being found at the same genomic locus in all 4 extant hyena species. Its coding sequence has further been maintained during all of Hyaenidae evolution. It is not found in any of the 30 other carnivorans—both Felidae and Canidae—that we screened. This Envelope protein does not disclose any fusogenic activity in ex vivo assays, at variance with the syncytin-Car1 Gene, which is found in all carnivorans, including the hyena, in which it is still present, transcriptionally active in the placenta, and fusogenic. Together, the present results illustrate the permanent renewal of placenta-specific Genes by retroviral capture and de facto provide a candidate Gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. IMPORTANCE The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral Envelope Genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral Envelope Gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared syncytin-Car1 Gene. This new env Gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.

  • retroviral Envelope Gene captures and syncytin exaptation for placentation in marsupials
    Proceedings of the National Academy of Sciences of the United States of America, 2015
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Quentin Carradec, Sylvie Souquere, Baptiste Mulot, Francois Catzeflis, Maria A Nilsson, Brandon R Menzies, Marilyn B Renfree
    Abstract:

    Syncytins are Genes of retroviral origin captured by eutherian mammals, with a role in placentation. Here we show that some marsupials—which are the closest living relatives to eutherian mammals, although they diverged from the latter ∼190 Mya—also possess a syncytin Gene. The Gene identified in the South American marsupial opossum and dubbed syncytin-Opo1 has all of the characteristic features of a bona fide syncytin Gene: It is fusogenic in an ex vivo cell–cell fusion assay; it is specifically expressed in the short-lived placenta at the level of the syncytial feto–maternal interface; and it is conserved in a functional state in a series of Monodelphis species. We further identify a nonfusogenic retroviral Envelope Gene that has been conserved for >80 My of evolution among all marsupials (including the opossum and the Australian tammar wallaby), with evidence for purifying selection and conservation of a canonical immunosuppressive domain, but with only limited expression in the placenta. This unusual captured Gene, together with a third class of Envelope Genes from recently endogenized retroviruses—displaying strong expression in the uterine glands where retroviral particles can be detected—plausibly correspond to the different evolutionary statuses of a captured retroviral Envelope Gene, with only syncytin-Opo1 being the present-day bona fide syncytin active in the opossum and related species. This study would accordingly recapitulate the natural history of syncytin exaptation and evolution in a single species, and definitely extends the presence of such Genes to all major placental mammalian clades.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of Virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud Tennant, Anne Dupressoir
    Abstract:

    Syncytin Genes are fusogenic Envelope protein (env) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by quantitative reverse transcription-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 million years ago, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven Syncytin Genes identified to date in eutherian mammals and is likely to be a major effector of placentation in its related clade. Importance: Syncytin Genes are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a Syncytin: it is specifically expressed in the placenta of the woodchuck Marmota monax, at the level of cells fusing into a syncytium; it can trigger cell-cell and virus-cell fusion ex vivo; and it has been conserved for >25 million years of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other Syncytin Genes identified thus far in mammals (primates, muroids, carnivores, and ruminants). These results extend the range of retroviral Envelope Gene "domestication" in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud C. Tennant, Anne Dupressoir
    Abstract:

    Syncytins are fusogenic Envelope protein ( env ) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by qRT-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 Mya, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven syncytin Genes identified to date in eutherian mammals, and is likely to be a major effector of placentation in its related clade. IMPORTANCE Syncytins are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a syncytin : it is specifically expressed in the placenta of the woodchuck Marmota monax , at the level of cells fusing into a syncytium, it can trigger cell-cell and virus-cell fusion ex vivo , it has been conserved for >25 My of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other syncytins identified so far in mammals (primates, muroids, carnivores and ruminants). These results extend the range of retroviral Envelope Gene ‘domestication’ in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Differential evolutionary fate of an ancestral primate endogenous retrovirus Envelope Gene, the EnvV syncytin, captured for a function in placentation.
    PLoS genetics, 2013
    Co-Authors: Cécile Esnault, Guillaume Cornelis, Odile Heidmann, Thierry Heidmann
    Abstract:

    Syncytins are Envelope Genes of retroviral origin that have been co-opted for a role in placentation. They promote cell–cell fusion and are involved in the formation of a syncytium layer—the syncytiotrophoblast—at the materno-fetal interface. They were captured independently in eutherian mammals, and knockout mice demonstrated that they are absolutely required for placenta formation and embryo survival. Here we provide evidence that these “necessary” Genes acquired “by chance” have a definite lifetime with diverse fates depending on the animal lineage, being both gained and lost in the course of evolution. Analysis of a retroviral Envelope Gene, the envV Gene, present in primate genomes and belonging to the endogenous retrovirus type V (ERV-V) provirus, shows that this captured Gene, which entered the primate lineage >45 million years ago, behaves as a syncytin in Old World monkeys, but lost its canonical fusogenic activity in other primate lineages, including humans. In the Old World monkeys, we show—by in situ analyses and ex vivo assays—that envV is both specifically expressed at the level of the placental syncytiotrophoblast and fusogenic, and that it further displays signs of purifying selection based on analysis of non-synonymous to synonymous substitution rates. We further show that purifying selection still operates in the primate lineages where the Gene is no longer fusogenic, indicating that deGeneracy of this ancestral syncytin is a slow, lineage-dependent, and multi-step process, in which the fusogenic activity would be the first canonical property of this retroviral Envelope Gene to be lost.

Odile Heidmann - One of the best experts on this subject based on the ideXlab platform.

  • capture of a hyena specific retroviral Envelope Gene with placental expression associated in evolution with the unique emergence among carnivorans of hemochorial placentation in hyaenidae
    Journal of Virology, 2018
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Odile Heidmann, Anne Dupressoir, Mathis Funk
    Abstract:

    ABSTRACT Capture of retroviral Envelope Genes from endogenous retroviruses has played a role in the evolution of mammals, with evidence for the involvement of these Genes in the formation of the maternofetal interface of the placenta. It has been shown that the diversity of captured Genes is likely to be responsible for the diversity of placental structures, ranging from poorly invasive (epitheliochorial) to highly invasive (hemochorial), with an intermediate state (endotheliochorial) as found in carnivorans. The latter recapitulate part of this evolution, with the hyena being the sole carnivoran with a hemochorial placenta. In this study, we performed RNA sequencing on hyena placental transcripts and searched for endogenous retroviral Envelope Genes that have been captured specifically in the Hyaenidae clade and are not found in any other carnivoran. We identified an Envelope Gene that is expressed in the placenta at the level of the maternofetal interface, as evidenced by in situ hybridization/immunohistochemistry. The Gene entry is coincidental with the emergence of the Hyaenidae clade 30 million years ago (Mya), being found at the same genomic locus in all 4 extant hyena species. Its coding sequence has further been maintained during all of Hyaenidae evolution. It is not found in any of the 30 other carnivorans—both Felidae and Canidae—that we screened. This Envelope protein does not disclose any fusogenic activity in ex vivo assays, at variance with the syncytin-Car1 Gene, which is found in all carnivorans, including the hyena, in which it is still present, transcriptionally active in the placenta, and fusogenic. Together, the present results illustrate the permanent renewal of placenta-specific Genes by retroviral capture and de facto provide a candidate Gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. IMPORTANCE The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral Envelope Genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral Envelope Gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared syncytin-Car1 Gene. This new env Gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of Virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud Tennant, Anne Dupressoir
    Abstract:

    Syncytin Genes are fusogenic Envelope protein (env) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by quantitative reverse transcription-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 million years ago, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven Syncytin Genes identified to date in eutherian mammals and is likely to be a major effector of placentation in its related clade. Importance: Syncytin Genes are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a Syncytin: it is specifically expressed in the placenta of the woodchuck Marmota monax, at the level of cells fusing into a syncytium; it can trigger cell-cell and virus-cell fusion ex vivo; and it has been conserved for >25 million years of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other Syncytin Genes identified thus far in mammals (primates, muroids, carnivores, and ruminants). These results extend the range of retroviral Envelope Gene "domestication" in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud C. Tennant, Anne Dupressoir
    Abstract:

    Syncytins are fusogenic Envelope protein ( env ) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by qRT-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 Mya, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven syncytin Genes identified to date in eutherian mammals, and is likely to be a major effector of placentation in its related clade. IMPORTANCE Syncytins are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a syncytin : it is specifically expressed in the placenta of the woodchuck Marmota monax , at the level of cells fusing into a syncytium, it can trigger cell-cell and virus-cell fusion ex vivo , it has been conserved for >25 My of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other syncytins identified so far in mammals (primates, muroids, carnivores and ruminants). These results extend the range of retroviral Envelope Gene ‘domestication’ in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Differential evolutionary fate of an ancestral primate endogenous retrovirus Envelope Gene, the EnvV syncytin, captured for a function in placentation.
    PLoS genetics, 2013
    Co-Authors: Cécile Esnault, Guillaume Cornelis, Odile Heidmann, Thierry Heidmann
    Abstract:

    Syncytins are Envelope Genes of retroviral origin that have been co-opted for a role in placentation. They promote cell–cell fusion and are involved in the formation of a syncytium layer—the syncytiotrophoblast—at the materno-fetal interface. They were captured independently in eutherian mammals, and knockout mice demonstrated that they are absolutely required for placenta formation and embryo survival. Here we provide evidence that these “necessary” Genes acquired “by chance” have a definite lifetime with diverse fates depending on the animal lineage, being both gained and lost in the course of evolution. Analysis of a retroviral Envelope Gene, the envV Gene, present in primate genomes and belonging to the endogenous retrovirus type V (ERV-V) provirus, shows that this captured Gene, which entered the primate lineage >45 million years ago, behaves as a syncytin in Old World monkeys, but lost its canonical fusogenic activity in other primate lineages, including humans. In the Old World monkeys, we show—by in situ analyses and ex vivo assays—that envV is both specifically expressed at the level of the placental syncytiotrophoblast and fusogenic, and that it further displays signs of purifying selection based on analysis of non-synonymous to synonymous substitution rates. We further show that purifying selection still operates in the primate lineages where the Gene is no longer fusogenic, indicating that deGeneracy of this ancestral syncytin is a slow, lineage-dependent, and multi-step process, in which the fusogenic activity would be the first canonical property of this retroviral Envelope Gene to be lost.

Cecile Vernochet - One of the best experts on this subject based on the ideXlab platform.

  • capture of a hyena specific retroviral Envelope Gene with placental expression associated in evolution with the unique emergence among carnivorans of hemochorial placentation in hyaenidae
    Journal of Virology, 2018
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Odile Heidmann, Anne Dupressoir, Mathis Funk
    Abstract:

    ABSTRACT Capture of retroviral Envelope Genes from endogenous retroviruses has played a role in the evolution of mammals, with evidence for the involvement of these Genes in the formation of the maternofetal interface of the placenta. It has been shown that the diversity of captured Genes is likely to be responsible for the diversity of placental structures, ranging from poorly invasive (epitheliochorial) to highly invasive (hemochorial), with an intermediate state (endotheliochorial) as found in carnivorans. The latter recapitulate part of this evolution, with the hyena being the sole carnivoran with a hemochorial placenta. In this study, we performed RNA sequencing on hyena placental transcripts and searched for endogenous retroviral Envelope Genes that have been captured specifically in the Hyaenidae clade and are not found in any other carnivoran. We identified an Envelope Gene that is expressed in the placenta at the level of the maternofetal interface, as evidenced by in situ hybridization/immunohistochemistry. The Gene entry is coincidental with the emergence of the Hyaenidae clade 30 million years ago (Mya), being found at the same genomic locus in all 4 extant hyena species. Its coding sequence has further been maintained during all of Hyaenidae evolution. It is not found in any of the 30 other carnivorans—both Felidae and Canidae—that we screened. This Envelope protein does not disclose any fusogenic activity in ex vivo assays, at variance with the syncytin-Car1 Gene, which is found in all carnivorans, including the hyena, in which it is still present, transcriptionally active in the placenta, and fusogenic. Together, the present results illustrate the permanent renewal of placenta-specific Genes by retroviral capture and de facto provide a candidate Gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. IMPORTANCE The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral Envelope Genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral Envelope Gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared syncytin-Car1 Gene. This new env Gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.

  • retroviral Envelope Gene captures and syncytin exaptation for placentation in marsupials
    Proceedings of the National Academy of Sciences of the United States of America, 2015
    Co-Authors: Guillaume Cornelis, Cecile Vernochet, Quentin Carradec, Sylvie Souquere, Baptiste Mulot, Francois Catzeflis, Maria A Nilsson, Brandon R Menzies, Marilyn B Renfree
    Abstract:

    Syncytins are Genes of retroviral origin captured by eutherian mammals, with a role in placentation. Here we show that some marsupials—which are the closest living relatives to eutherian mammals, although they diverged from the latter ∼190 Mya—also possess a syncytin Gene. The Gene identified in the South American marsupial opossum and dubbed syncytin-Opo1 has all of the characteristic features of a bona fide syncytin Gene: It is fusogenic in an ex vivo cell–cell fusion assay; it is specifically expressed in the short-lived placenta at the level of the syncytial feto–maternal interface; and it is conserved in a functional state in a series of Monodelphis species. We further identify a nonfusogenic retroviral Envelope Gene that has been conserved for >80 My of evolution among all marsupials (including the opossum and the Australian tammar wallaby), with evidence for purifying selection and conservation of a canonical immunosuppressive domain, but with only limited expression in the placenta. This unusual captured Gene, together with a third class of Envelope Genes from recently endogenized retroviruses—displaying strong expression in the uterine glands where retroviral particles can be detected—plausibly correspond to the different evolutionary statuses of a captured retroviral Envelope Gene, with only syncytin-Opo1 being the present-day bona fide syncytin active in the opossum and related species. This study would accordingly recapitulate the natural history of syncytin exaptation and evolution in a single species, and definitely extends the presence of such Genes to all major placental mammalian clades.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of Virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud Tennant, Anne Dupressoir
    Abstract:

    Syncytin Genes are fusogenic Envelope protein (env) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by quantitative reverse transcription-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 million years ago, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven Syncytin Genes identified to date in eutherian mammals and is likely to be a major effector of placentation in its related clade. Importance: Syncytin Genes are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a Syncytin: it is specifically expressed in the placenta of the woodchuck Marmota monax, at the level of cells fusing into a syncytium; it can trigger cell-cell and virus-cell fusion ex vivo; and it has been conserved for >25 million years of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other Syncytin Genes identified thus far in mammals (primates, muroids, carnivores, and ruminants). These results extend the range of retroviral Envelope Gene "domestication" in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.

  • Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade
    Journal of virology, 2014
    Co-Authors: François Redelsperger, Guillaume Cornelis, Cecile Vernochet, Baptiste Mulot, Francois Catzeflis, Odile Heidmann, Thierry Heidmann, Bud C. Tennant, Anne Dupressoir
    Abstract:

    Syncytins are fusogenic Envelope protein ( env ) Genes of retroviral origin that have been captured for a function in placentation. Within rodents, two such Genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. Here, we searched for similar Genes in a second major clade of the Rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel Ictidomys tridecemlineatus genome. In silico search for env Genes with full coding capacity identified several candidate Genes with one displaying placenta-specific expression, as revealed by qRT-PCR analysis of a large panel of tissues. This Gene belongs to a deGenerate endogenous retroviral element, with recognizable hallmarks of an integrated provirus. Cloning of the Gene in an expression vector for ex vivo cell-cell fusion and pseudotype assays demonstrated fusogenicity on a large panel of mammalian cells. In situ hybridization on placenta sections showed specific expression in domains where trophoblast cells fuse into a syncytiotrophoblast at the fetomaternal interface, consistent with a role in syncytium formation. Finally, we show that the Gene is conserved among the tribe Marmotini, thus dating its capture back to about at least 25 Mya, with evidence for purifying selection and conservation of fusogenic activity. This Gene that we named syncytin-Mar1 is distinct from all seven syncytin Genes identified to date in eutherian mammals, and is likely to be a major effector of placentation in its related clade. IMPORTANCE Syncytins are fusogenic Envelope Genes of retroviral origin, ancestrally captured for a function in placentation. Within rodents, two such Genes had been previously identified in the mouse-related clade. Here, in the squirrel-related rodent clade, we identified the Envelope Gene of an endogenous retrovirus with all the features of a syncytin : it is specifically expressed in the placenta of the woodchuck Marmota monax , at the level of cells fusing into a syncytium, it can trigger cell-cell and virus-cell fusion ex vivo , it has been conserved for >25 My of evolution, suggesting an essential role in its host physiology. Remarkably, syncytin-Mar1 is unrelated to all other syncytins identified so far in mammals (primates, muroids, carnivores and ruminants). These results extend the range of retroviral Envelope Gene ‘domestication’ in mammals and show that these events occurred independently, on multiple occasions during evolution to improve placental development in a process of convergent evolution.