Evolutionary History of GLIS Genes Illuminates Their Roles in Cell Reprograming and Ciliogenesis
Evolutionary History of GLIS Genes Illuminates Their Roles in Cell Reprograming and Ciliogenesis
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DOI：
10.1093/molbev/msz205
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发表时间：
2019-09
影响因子：
10.7
通讯作者：
Yuuri Yasuoka;M. Matsumoto;K. Yagi;Y. Okazaki
中科院分区：
文献类型：
--
作者：
Yuuri Yasuoka;M. Matsumoto;K. Yagi;Y. Okazaki
摘要GLIS家族转录因子GLIS 1和GLIS 3促进诱导多能干细胞（iPSCs）的产生。相反，另一个GLIS家族成员GLIS 2抑制细胞重编程。为了理解这些不同的角色是如何产生的，我们研究了GLIS基因的进化起源和基因组组织。系统发育分析表明，GLIS 1和GLIS 3起源于脊椎动物全基因组复制，而GLIS 2是GLIS 1/3和GLI家族的姐妹群。这一结果与它们在细胞重编程中的相反功能一致。Glis 1比Glis 3进化得更快，失去了许多蛋白质相互作用的基序。这表明Glis 1在进化限制减弱的情况下获得了新的功能。事实上，GLIS 1诱导诱导多能干细胞的能力更强。从各种动物胚胎的转录组学数据表明，glis 1是母系表达在一些四足动物，而脊椎动物glis 3和无脊椎动物glis 1/3基因很少在卵母细胞中表达，这表明脊椎动物（或四足动物）glis 1获得了一个新的表达域和功能作为一个母亲的因素。此外，比较基因组分析表明，glis 1/3与rfx 3、ndc 1、hspb 11和lrrc 42一起是双侧特异性基因簇的一部分。因为这些基因的已知功能与纤毛的形成和功能有关，所以两侧对称动物的最后共同祖先可能通过改组基因顺序来建立涉及纤毛的更复杂的上皮组织而获得了该簇。这项进化研究强调了GLIS 1/3对细胞重编程，发育和纤毛器官（如肺，肾和胰腺）疾病的重要性。
Abstract The GLIS family transcription factors, GLIS1 and GLIS3, potentiate generation of induced pluripotent stem cells (iPSCs). In contrast, another GLIS family member, GLIS2, suppresses cell reprograming. To understand how these disparate roles arose, we examined evolutionary origins and genomic organization of GLIS genes. Comprehensive phylogenetic analysis shows that GLIS1 and GLIS3 originated during vertebrate whole genome duplication, whereas GLIS2 is a sister group to the GLIS1/3 and GLI families. This result is consistent with their opposing functions in cell reprograming. Glis1 evolved faster than Glis3, losing many protein-interacting motifs. This suggests that Glis1 acquired new functions under weakened evolutionary constraints. In fact, GLIS1 induces induced pluripotent stem cells more strongly. Transcriptomic data from various animal embryos demonstrate that glis1 is maternally expressed in some tetrapods, whereas vertebrate glis3 and invertebrate glis1/3 genes are rarely expressed in oocytes, suggesting that vertebrate (or tetrapod) Glis1 acquired a new expression domain and function as a maternal factor. Furthermore, comparative genomic analysis reveals that glis1/3 is part of a bilaterian-specific gene cluster, together with rfx3, ndc1, hspb11, and lrrc42. Because known functions of these genes are related to cilia formation and function, the last common ancestor of bilaterians may have acquired this cluster by shuffling gene order to establish more sophisticated epithelial tissues involving cilia. This evolutionary study highlights the significance of GLIS1/3 for cell reprograming, development, and diseases in ciliated organs such as lung, kidney, and pancreas.