硬骨鱼Ep300复制体的定向分化及其意义

IF 3.4 Q1 Agricultural and Biological Sciences
Xianzong Wang, Junli Yan
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引用次数: 0

摘要

EP300是脊椎动物中的一种保守蛋白,在细胞稳态中起着重要的调节作用。EP300的突变和失调导致严重的人类发育障碍和恶性肿瘤。瘤胃瘤胃是研究EP300相关疾病和药物的良好模式生物;然而,来自硬骨鱼特异性全基因组复制的EP300副本的影响不应被忽视。结果本研究获得了具有代表性的硬骨鱼、哺乳动物和蜥脚类动物的EP300蛋白序列,并推断出高度支持的最大似然树。我们观察到Ep300重复序列(Ep300a和Ep300b)在硬骨鱼中广泛保留,并在多种组织中普遍表达。Ep300a和Ep300b的共识序列保守结构域分布完全相同,表明它们的功能仍有很大的重叠。采用分支位点模型、进化枝模型和位点模型分析了硬骨鱼Ep300重复序列的分子进化。结果表明,这两个重复都受到强阳性选择的影响;然而,对于一个现存物种来说,通常最多有一个拷贝处于正选择状态。在支系水平上,进化速率、正选择位点数量与基因表达水平之间存在显著正相关。在牡蛎中,Ep300a比Ep300b受到更强的正选择;在另一个种类丰富的硬骨鱼分支新硬骨鱼中,情况正好相反。我们还模拟了D. rerio和Oryzias latipes的Ep300a和Ep300b的zf-TAZ结构域及其侧翼区域的三维结构,发现在这两个物种中,更快进化的拷贝具有更多的短螺旋。总的来说,Ep300的两个拷贝在硬骨鱼的主要分支中无疑经历了方向性分化。EP300在硬骨鱼和哺乳动物之间的差异应该大于不同硬骨鱼支系之间的差异。需要进一步的研究来阐明EP300参与的调节网络在硬骨鱼和哺乳动物之间的差异程度,这也有助于解释硬骨鱼的巨大成功。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Directional divergence of Ep300 duplicates in teleosts and its implications
Background EP300 is a conserved protein in vertebrates, which serves as a key mediator of cellular homeostasis. Mutations and dysregulation of EP300 give rise to severe human developmental disorders and malignancy. Danio rerio is a promising model organism to study EP300 related diseases and drugs; however, the effect of EP300 duplicates derived from teleost-specific whole genome duplication should not just be neglected. Results In this study, we obtained EP300 protein sequences of representative teleosts, mammals and sauropsids, with which we inferred a highly supported maximum likelihood tree. We observed that Ep300 duplicates (Ep300a and Ep300b) were widely retained in teleosts and universally expressed in a variety of tissues. Consensus sequences of Ep300a and Ep300b had exactly the same distribution of conserved domains, suggesting that their functions should still be largely overlapped. We analyzed the molecular evolution of Ep300 duplicates in teleosts, using branch-site models, clade models and site models. The results showed that both duplicates were subject to strong positive selection; however, for an extant species, generally at most one copy was under positive selection. At the clade level, there were evident positive correlations between evolutionary rates, the number of positively selected sites and gene expression levels. In Ostariophysi, Ep300a were under stronger positive selection than Ep300b; in Neoteleostei, another species-rich teleost clade, the contrary was the case. We also modeled 3D structures of zf-TAZ domain and its flanking regions of Ep300a and Ep300b of D. rerio and Oryzias latipes and found that in either species the faster evolving copy had more short helixes. Conclusions Collectively, the two copies of Ep300 have undoubtedly experienced directional divergence in main teleost clades. The divergence of EP300 between teleosts and mammals should be greater than the divergence between different teleost clades. Further studies are needed to clarify to what extent the EP300 involved regulatory network has diverged between teleosts and mammals, which would also help explain the huge success of teleosts.
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来源期刊
BMC Evolutionary Biology
BMC Evolutionary Biology 生物-进化生物学
CiteScore
5.80
自引率
0.00%
发文量
0
审稿时长
6 months
期刊介绍: BMC Evolutionary Biology is an open access, peer-reviewed journal that considers articles on all aspects of molecular and non-molecular evolution of all organisms, as well as phylogenetics and palaeontology.
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