Scerbo Pierluigi, Markov Gabriel V, Vivien Céline, Kodjabachian Laurent, Demeneix Barbara, Coen Laurent, Girardot Fabrice
Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France ; Institut de Biologie du Développement de Marseille, Aix-Marseille Université, Centre National de la Recherche Scientifique, Marseille, France.
Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France ; Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Lyon, France ; Department for Evolutionary Biology, Max-Planck-Institute for Developmental Biology, Tuebingen, Germany.
PLoS One. 2014 Jan 17;9(1):e85104. doi: 10.1371/journal.pone.0085104. eCollection 2014.
Though pluripotency is well characterized in mammals, many questions remain to be resolved regarding its evolutionary history. A necessary prerequisite for addressing this issue is to determine the phylogenetic distributions and orthology relationships of the transcription factor families sustaining or modulating this property. In mammals, the NANOG homeodomain transcription factor is one of the core players in the pluripotency network. However, its evolutionary history has not been thoroughly studied, hindering the interpretation of comparative studies. To date, the NANOG family was thought to be monogenic, with numerous pseudogenes described in mammals, including a tandem duplicate in Hominidae. By examining a wide-array of craniate genomes, we provide evidence that the NANOG family arose at the latest in the most recent common ancestor of osteichthyans and that NANOG genes are frequently found as tandem duplicates in sarcopterygians and as a single gene in actinopterygians. Their phylogenetic distribution is thus reminiscent of that recently shown for Class V POU paralogues, another key family of pluripotency-controlling factors. However, while a single ancestral duplication has been reported for the Class V POU family, we suggest that multiple independent duplication events took place during evolution of the NANOG family. These multiple duplications could have contributed to create a layer of complexity in the control of cell competence and pluripotency, which could explain the discrepancies relative to the functional evolution of this important gene family. Further, our analysis does not support the hypothesis that loss of NANOG and emergence of the preformation mode of primordial germ cell specification are causally linked. Our study therefore argues for the need of further functional comparisons between NANOG paralogues, notably regarding the novel duplicates identified in sauropsids and non-eutherian mammals.
尽管多能性在哺乳动物中已得到充分表征，但关于其进化历史仍有许多问题有待解决。解决这一问题的一个必要前提是确定维持或调节这一特性的转录因子家族的系统发育分布和直系同源关系。在哺乳动物中，NANOG同源结构域转录因子是多能性网络的核心参与者之一。然而，其进化历史尚未得到充分研究，这阻碍了比较研究的解释。迄今为止，NANOG家族被认为是单基因的，在哺乳动物中描述了许多假基因，包括人科中的一个串联重复基因。通过检查一系列有头类动物的基因组，我们提供的证据表明，NANOG家族最晚出现在硬骨鱼最近的共同祖先中，并且NANOG基因在肉鳍鱼类中经常作为串联重复基因出现，而在辐鳍鱼类中则作为单个基因出现。因此，它们的系统发育分布让人联想到最近显示的V类POU旁系同源物的分布，V类POU旁系同源物是另一个控制多能性的关键家族。然而，虽然V类POU家族已报道有一次祖先重复事件，但我们认为在NANOG家族的进化过程中发生了多次独立的重复事件。这些多次重复可能导致在细胞能力和多能性控制方面产生一层复杂性，这可以解释与这个重要基因家族功能进化相关的差异。此外，我们的分析不支持NANOG缺失与原始生殖细胞特化的预成型模式出现存在因果关系的假设。因此，我们的研究主张需要对NANOG旁系同源物进行进一步的功能比较，特别是关于在蜥形纲动物和非真兽类哺乳动物中鉴定出的新重复基因。
