Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif, France.
Placenta. 2011 Nov;32(11):885-92. doi: 10.1016/j.placenta.2011.08.006. Epub 2011 Sep 3.
Syncytins are genes of retroviral origin that have been co-opted by mammalian hosts for a function in placentation. Two such genes have already been identified in simians, as well as two distinct, unrelated ones in Muridae and a fifth in the rabbit. Here we searched for similar genes in the guinea pig, which belongs to the Caviomorpha lineage within the Hystricognathi suborder of rodents and displays a placental structural organization with several characteristic features comparable to those of the human organ, including deep trophoblast invasion of maternal tissues. An in silico search for envelope (env) genes with full coding capacity identified a candidate gene that showed specific expression in the placenta, as revealed by RT-qPCR using RNAs from a large panel of tissues. This gene belongs to an endogenous retroviral element present at a single-copy in the guinea pig genome, still displaying a retroviral organization - with a degenerate gag and pol, but an intact env gene. In situ hybridization of guinea pig placenta sections demonstrated specific expression at the level of the invasive trophoblast-containing junctional zone, as observed in humans for syncytin-1 and consistent with a role in invasion of the maternal uterine tissues. The identified gene displays a conserved open reading frame in the Caviomorpha, consistent with an entry date >30 million years, and sequence analyses showed purifying selection of the gene. Conclusively, despite the absence of a demonstrated fusogenic activity, it is likely that the identified env gene - that we named syncytin-like env-Cav1 - exerts a physiological function possibly related to trophoblast invasion, in the course of caviomorph placentation.
合胞素是逆转录病毒起源的基因,已被哺乳动物宿主共同用于胎盘形成的功能。在灵长类动物中已经鉴定出了两个这样的基因,在鼠科动物中有两个不同的、不相关的基因,在兔中还有第五个基因。在这里,我们在豚鼠中搜索了类似的基因,豚鼠属于啮齿动物的豪猪亚目,其胎盘结构组织与人类器官具有几个相似的特征,包括滋养层对母体组织的深度入侵。通过对具有完整编码能力的包膜(env)基因进行计算机搜索,鉴定出了一个候选基因,该基因在胎盘中有特异性表达,这是通过使用来自大量组织的 RNA 进行 RT-qPCR 揭示的。该基因属于豚鼠基因组中单拷贝存在的内源性逆转录病毒元件,仍然显示出逆转录病毒的组织——退化的 gag 和 pol,但完整的 env 基因。豚鼠胎盘切片的原位杂交显示,在含有侵袭性滋养层的连接区水平上有特异性表达,这与人类的 syncytin-1 观察结果一致,表明其在侵袭母体子宫组织中发挥作用。鉴定出的基因在豪猪亚目中显示出保守的开放阅读框,与 3000 多万年前的进入日期一致,序列分析表明该基因受到了净化选择。总之,尽管没有证明融合活性,但鉴定出的 env 基因——我们命名为 syncytin-like env-Cav1——很可能在豪猪亚目胎盘形成过程中发挥了一种与滋养层入侵相关的生理功能。