Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Villejuif, France.
UMR 9196, Université Paris-Sud, Orsay, France.
J Virol. 2019 Feb 5;93(4). doi: 10.1128/JVI.01811-18. Print 2019 Feb 15.
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 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 assays, at variance with the 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 provide a candidate gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral envelope genes. In carnivorans, capture of 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 gene. This new gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.
从内源性逆转录病毒中捕获逆转录病毒包膜基因在哺乳动物的进化中发挥了作用，有证据表明这些基因参与了胎盘母体-胎儿界面的形成。研究表明，捕获基因的多样性可能是胎盘结构多样性的原因，从侵袭性差（上皮绒毛膜）到侵袭性高（血绒毛膜），而中间状态（内皮绒毛膜）在食肉动物中发现。后者部分再现了这一进化，土狼是唯一具有血绒毛膜胎盘的食肉动物。在这项研究中，我们对土狼胎盘转录本进行了 RNA 测序，并寻找了在 Hyaenidae 进化枝中特异性捕获且不在任何其他食肉动物中发现的内源性逆转录病毒包膜基因。我们鉴定了一个在胎盘母体-胎儿界面表达的包膜基因，杂交/免疫组织化学证实了这一点。该基因的进入与 3000 万年前（Mya）出现的 Hyaenidae 进化枝同时发生，在所有 4 种现存的土狼物种中都位于相同的基因组位置。其编码序列在 Hyaenidae 的整个进化过程中都得到了进一步的维持。在我们筛选的 30 种其他食肉动物（包括猫科动物和犬科动物）中都没有发现这种包膜蛋白。这种包膜蛋白在实验中没有显示出任何融合活性，与所有食肉动物（包括土狼）中发现的基因不同，在这些动物中，该基因仍然存在，在胎盘中转录活跃，并具有融合活性。总之，本研究结果说明了通过逆转录病毒捕获来不断更新胎盘特异性基因，并为食肉动物中 Hyaenidae 从内皮绒毛膜到血绒毛膜的过渡提供了候选基因。胎盘是哺乳动物中最多样化的器官，部分原因是随机捕获逆转录病毒包膜基因。在食肉动物中，8000 万年前发生了 的捕获。它具有融合活性，在合胞体胎盘母体-胎儿界面表达，并且在所有食肉动物中保守，这与它们共同的内皮绒毛膜胎盘一致。土狼是一个显著的例外，它们具有高度侵袭性的血绒毛膜胎盘，就像人类一样，在这种胎盘下，母体血管破裂导致母体血液浸润合胞体母体-胎儿界面。在这项研究中，我们鉴定了一个大约 3000 万年前发生的逆转录病毒包膜基因捕获和适应，与 Hyaenidae 的出现同时发生，在所有现存的土狼物种中都得到了保守。除了共享的 基因外，它还在母体-胎儿界面表达。这个新的 基因，不存在于任何其他食肉动物中，可能是负责土狼胎盘特定结构的候选基因。
