Surprising complexity of the ancestral apoptosis network.
Surprising complexity of the ancestral apoptosis network.
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DOI：
10.1186/gb-2007-8-10-r226
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Godzik A
中科院分区：
文献类型：
--
作者：
Zmasek CM;Zhang Q;Ye Y;Godzik A
比较基因组学方法表明，脊椎动物中具有单拷贝的凋亡网络的几个组成部分的基因在蛇行-双栖动物的祖先中具有多个平行序列，这表明该网络具有复杂的进化史。细胞凋亡是细胞程序性死亡的主要类型之一，由复杂的蛋白质网络调控和执行。在模式生物中的研究，主要是在线虫秀丽线虫中，发现了一个相对简单的只由几种蛋白质组成的凋亡网络。然而，对最近测序的几种无脊椎动物基因组的分析，从代表形态最简单的后生动物之一的刺海葵，到后口海胆和文昌鱼，与目前在脊椎动物中扩展的简单祖先网络的范式相矛盾。在这里，我们发现形成凋亡体的CED-4/APAF-1蛋白，在脊椎动物、线虫和昆虫基因组中以单拷贝形式存在，在线虫-双边动物的祖先中有多个旁系。这个祖先APAF-1家族的不同成员导致了线虫/昆虫和后口动物中现存的蛋白质，解释了到目前为止被认为是同源的蛋白质之间的显著功能差异。同样，Bcl2和Caspase蛋白家族的进化看起来出奇地复杂，显然包括线虫和昆虫中显著的基因丢失和后口动物的扩张。细胞凋亡网络进化的新图景是一系列谱系特有的扩展和丢失之一，再加上有限数量的“凋亡”蛋白家族，导致不同生物中的网络明显相似，掩盖了潜在的复杂进化史。类似的结果也开始出现在其他监管网络上，这与监管网络以线性方式从简单到复杂演变的直观概念相矛盾。
A comparative genomics approach revealed that the genes for several components of the apoptosis network with single copies in vertebrates have multiple paralogs in cnidarian-bilaterian ancestors, suggesting a complex evolutionary history for this network. Apoptosis, one of the main types of programmed cell death, is regulated and performed by a complex protein network. Studies in model organisms, mostly in the nematode Caenorhabditis elegans, identified a relatively simple apoptotic network consisting of only a few proteins. However, analysis of several recently sequenced invertebrate genomes, ranging from the cnidarian sea anemone Nematostella vectensis, representing one of the morphologically simplest metazoans, to the deuterostomes sea urchin and amphioxus, contradicts the current paradigm of a simple ancestral network that expanded in vertebrates. Here we show that the apoptosome-forming CED-4/Apaf-1 protein, present in single copy in vertebrate, nematode, and insect genomes, had multiple paralogs in the cnidarian-bilaterian ancestor. Different members of this ancestral Apaf-1 family led to the extant proteins in nematodes/insects and in deuterostomes, explaining significant functional differences between proteins that until now were believed to be orthologous. Similarly, the evolution of the Bcl-2 and caspase protein families appears surprisingly complex and apparently included significant gene loss in nematodes and insects and expansions in deuterostomes. The emerging picture of the evolution of the apoptosis network is one of a succession of lineage-specific expansions and losses, which combined with the limited number of 'apoptotic' protein families, resulted in apparent similarities between networks in different organisms that mask an underlying complex evolutionary history. Similar results are beginning to surface for other regulatory networks, contradicting the intuitive notion that regulatory networks evolved in a linear way, from simple to complex.
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