Evolution of increased complexity in a molecular machine.

Evolution of increased complexity in a molecular machine.
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DOI:
10.1038/nature10724
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发表时间:
2012-01-09
期刊:
影响因子:
64.8
通讯作者:
Thornton, Joseph W.
Thornton, Joseph W.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Finnigan, Gregory C.;Hanson-Smith, Victor;Stevens, Tom H.;Thornton, Joseph W.

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许多细胞过程是由分子“机器”进行的-多种分化蛋白质的组装,这些蛋白质通过物理相互作用来执行生物功能。尽管有很多猜测,但缺乏这些组件进化机制的有力证据。在这里,我们使用祖先基因复活和操纵遗传实验来确定一个重要的分子机器的复杂性-真核细胞V-ATP酶质子泵的六聚体跨膜环-在数亿年前增加。我们表明,真菌,这是由三个旁系同源蛋白质的环,从一个更古老的两个paradigs复杂的,因为基因重复,其次是在每个子拷贝的特定接口,它与其他环蛋白相互作用的损失。这些损失是互补的,因此两个副本成为在复合体中具有有限空间作用的专性组件。将来自每一个paradox谱系的单个历史突变重新引入到复活的祖先蛋白中足以重现它们的不对称变性,并触发对更复杂的三组分环的需求。我们的实验表明,在一个基本的分子机器进化的复杂性增加,因为简单的,高概率的进化过程,没有明显的新功能的进化。他们指出了一个合理的机制,复杂性的演变,在其他多partial蛋白质复合物。
Many cellular processes are carried out by molecular ‘machines’— assemblies of multiple differentiated proteins that physically interact to execute biological functions. Despite much speculation, strong evidence of the mechanisms by which these assemblies evolved is lacking. Here we use ancestral gene resurrectionand manipulative genetic experiments to determine how the complexity of an essential molecular machine—the hexameric transmembrane ring of the eukaryotic V-ATPase proton pump—increased hundreds of millions of years ago. We show that the ring of Fungi, which is composed of three paralogous proteins, evolved from a more ancient two-paralogue complex because of a gene duplication that was followed by loss in each daughter copy of specific interfaces by which it interacts with other ring proteins. These losses were complementary, so both copies became obligate components with restricted spatial roles in the complex. Reintroducing a single historical mutation from each paralogue lineage into the resurrected ancestral proteins is sufficient to recapitulate their asymmetric degeneration and trigger the requirement for the more elaborate three-component ring. Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.
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