Origins of amyloid-β.
Origins of amyloid-β.
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DOI：
10.1186/1471-2164-14-290
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发表时间：
2013-04-30
期刊：
影响因子：
4.4
通讯作者：
Sarkar IN
中科院分区：
文献类型：
--
作者：
Tharp WG;Sarkar IN
淀粉样蛋白-β斑块是阿尔茨海默病的一个定义特征。然而，淀粉样蛋白-β沉积也在其他形式的痴呆症和非病理情况下发现。淀粉样蛋白-β的沉积在脊椎动物物种中是不同的，淀粉样蛋白致病特性的进化出现目前尚不清楚。病理性多肽序列的进化持久性可能取决于前体基因的功能、前体基因内核苷酸或多肽结构域的保守或突变，或者物种特有的生理环境。在这项研究中，我们使用为淀粉样蛋白前体蛋白基因家族构建的系统发育树，并通过模拟硅谷中淀粉样蛋白-β跨物种聚集的可能性，来询问淀粉样变性β最早出现的时间。我们使用自动化的迭代元数据库搜索收集了淀粉样蛋白-β前体蛋白家族最全面的一组序列，并构建了一个高度分辨的系统发育图。分析表明，无脊椎动物和脊椎动物淀粉样蛋白-β前体蛋白基因家族的祖先基因出现在埃迪卡拉纪的后生物种形成过程中。同形频率发现序列的区域特异性保守性。聚集势分析表明，潜在的淀粉样变序列是脊椎动物淀粉样蛋白-β前体蛋白普遍存在的特征，但也在棘皮动物、线虫、头索动物和膜翅目物种的同源物中发现。淀粉样蛋白-β前体蛋白基因由来已久，高度保守。淀粉样蛋白形成淀粉样蛋白-β结构域可能存在于后口动物的早期，但最近的突变似乎导致了潜在的无关的淀粉样蛋白形成序列。我们的结果进一步强调了物种特有的生理环境对淀粉样蛋白-β的形成与多肽序列一样关键。
Amyloid-β plaques are a defining characteristic of Alzheimer Disease. However, Amyloid-β deposition is also found in other forms of dementia and in non-pathological contexts. Amyloid-β deposition is variable among vertebrate species and the evolutionary emergence of the amyloidogenic property is currently unknown. Evolutionary persistence of a pathological peptide sequence may depend on the functions of the precursor gene, conservation or mutation of nucleotides or peptide domains within the precursor gene, or a species-specific physiological environment. In this study, we asked when amyloidogenic Amyloid-β first arose using phylogenetic trees constructed for the Amyloid-β Precursor Protein gene family and by modeling the potential for Amyloid-β aggregation across species in silico. We collected the most comprehensive set of sequences for the Amyloid-β Precursor Protein family using an automated, iterative meta-database search and constructed a highly resolved phylogeny. The analysis revealed that the ancestral gene for invertebrate and vertebrate Amyloid-β Precursor Protein gene families arose around metazoic speciation during the Ediacaran period. Synapomorphic frequencies found domain-specific conservation of sequence. Analyses of aggregation potential showed that potentially amyloidogenic sequences are a ubiquitous feature of vertebrate Amyloid-β Precursor Protein but are also found in echinoderm, nematode, and cephalochordate, and hymenoptera species homologues. The Amyloid-β Precursor Protein gene is ancient and highly conserved. The amyloid forming Amyloid-β domains may have been present in early deuterostomes, but more recent mutations appear to have resulted in potentially unrelated amyoid forming sequences. Our results further highlight that the species-specific physiological environment is as critical to Amyloid-β formation as the peptide sequence.
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影响因子：
64.8
作者：
BRACK, A;ORGEL, LE
通讯作者：
ORGEL, LE
树突镜：大型系统发育树的互动观众。
影响因子：
3
作者：
Huson, Daniel H.;Richter, Daniel C.;Rausch, Christian;Dezulian, Tobias;Franz, Markus;Rupp, Regula
通讯作者：
Rupp, Regula
影响因子：
3
作者：
Beach, Thomas G.
通讯作者：
Beach, Thomas G.
影响因子：
4.2
作者：
Flood, Dorothy G.;Lin, Yin-Guo;Howland, David S.
通讯作者：
Howland, David S.
影响因子：
6.1
作者：
Carmine-Simmen K;Proctor T;Tschäpe J;Poeck B;Triphan T;Strauss R;Kretzschmar D
通讯作者：
Kretzschmar D