NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human naïve pluripotent stem cells.
NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human naïve pluripotent stem cells.
复制标题
DOI：
10.1242/dev.201155
复制
发表时间：
2023-01-15
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
基因复制事件可以通过为新的基因功能提供遗传物质来驱动进化，并且它们为物种之间出现不同的发育策略创造机会。为了研究重复基因对人类早期发育的贡献，我们检查了 NANOGP1（转录因子 NANOG 的串联重复）的进化和功能。我们发现NANOGP1和NANOG具有重叠但不同的表达谱，其中NANOGP1的高表达仅限于早期外胚层细胞和幼稚态多能干细胞。序列分析和表位标记表明 NANOGP1 是具有完整同源盒结构域的蛋白质编码。创造 NANOGP1 的复制在灵长类动物进化中发生的时间比之前认为的要早，并且仅在类人猿中保留，而旧大陆猴子以不同的方式禁用了该基因，包括同源域点突变。 NANOGP1 是幼稚多能性的强诱导剂；然而，与 NANOG 不同的是，它不需要维持人类幼稚多能细胞的未分化状态。通过保留其祖先副本的表达、序列和部分功能保守性，NANOGP1 举例说明了基因复制和亚功能化如何促进人类多能性和发育中的转录因子活性。 确定 NANOGP1 与其祖先副本 NANOG 保留了部分功能保守性，揭示了基因复制和亚功能化在人类多能性和发育中的作用。
Gene duplication events can drive evolution by providing genetic material for new gene functions, and they create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naïve-state pluripotent stem cells. Sequence analysis and epitope-tagging revealed that NANOGP1 is protein coding with an intact homeobox domain. The duplication that created NANOGP1 occurred earlier in primate evolution than previously thought and has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways, including homeodomain point mutations. NANOGP1 is a strong inducer of naïve pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naïve pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development. Establishing that NANOGP1 has retained partial functional conservation with its ancestral copy NANOG sheds light on the role of gene duplication and subfunctionalisation in human pluripotency and development.
登录
查看更多内容
SRGAP2 人类特异性旁系同源物对 SRGAP2 功能的抑制可在脊柱成熟过程中诱导幼态持续
影响因子：
64.5
作者：
Charrier C;Joshi K;Coutinho-Budd J;Kim JE;Lambert N;de Marchena J;Jin WL;Vanderhaeghen P;Ghosh A;Sassa T;Polleux F
通讯作者：
Polleux F
影响因子：
4
作者：
Dennis MY;Eichler EE
通讯作者：
Eichler EE
影响因子：
3.4
作者：
Fairbanks DJ;Maughan PJ
通讯作者：
Maughan PJ
影响因子：
7.7
作者：
Dong, Chen;Beltcheva, Mariana;Theunissen, Thorold W.
通讯作者：
Theunissen, Thorold W.
影响因子：
5.9
作者：
Cinkornpumin, Jessica K.;Kwon, Sin Young;Pastor, William A.
通讯作者：
Pastor, William A.