在动物中通过Cdx2介导的转录调节的进化分析
Weizheng Liang1,2,3,4, Guipeng Li2,3,5, Yukai Wang6,7,8,9
1Hebei Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.
Cell proliferation
|July 29, 2025
概括
转录因子DNA结合域 (DBDs) 的进化变化可以推动表型多样性. 鼠标Cdx2 (mCdx2) 显示了潜在的积极选择,但它的功能效应和特定氨基酸变化的效应与老鼠Cdx2 (rCdx2) 相比保留了.
科学领域:
- 进化生物学是进化的生物学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 现型多样性源于基因表达的变化,这是由于调节元素分歧或转录因子 (TF) 结合的改变引起的.
- 虽然非编码元素的进化速度很快,但TF DNA结合域 (TF-DBD) 的进化速度较慢,但如果有益,则可能具有影响力.
研究的目的:
- 研究小鼠TF Cdx2DNA结合域 (mCdx2) 中潜在的阳性选择及其功能后果.
- 探索mCdx2中的特定氨基酸变化对其功能和基因调节的影响,与它的老鼠同类 (rCdx2) 相比.
主要方法:
- 蛋白序列分析以确定TF-DBDs中的保存和分离区域.
- 多omics分析以评估mCdx2和rCdx2.2之间的功能差异.
- 鼠-小鼠全二倍体胚胎干细胞研究,以检查对基因调节的cis效应.
主要成果:
- 在脊椎动物中观察到TF Cdx2 DBD的高保育率,mCdx2中的三个独特的氨基酸变化表明了潜在的积极选择.
- 在mCdx2和rCdx2之间没有发现任何显著的功能差异;确定的氨基酸变化没有影响功能.
- 在老鼠和老鼠之间,Cdx2的结合部位显著差异,但Cdx2的转录效应在很大程度上保持不变.
结论:
- 特定物种的TF-DBD变化可能并不总是导致功能差异,即使有积极选择的证据.
- 尽管存在不同的TF结合,但仍保留着转录效应,这表明了复杂的调控进化.
- 基因调节的进化涉及TF结合特异性和下游转录结果之间的相互作用.
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