Evolution of an ancient protein function involved in organized multicellularity in animals.
Evolution of an ancient protein function involved in organized multicellularity in animals.
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DOI：
10.7554/elife.10147
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发表时间：
2016-01-07
期刊：
影响因子：
7.7
通讯作者：
Prehoda KE
中科院分区：
文献类型：
--
作者：
Anderson DP;Whitney DS;Hanson-Smith V;Woznica A;Campodonico-Burnett W;Volkman BF;King N;Thornton JW;Prehoda KE
为了形成和维持有组织的组织，多细胞生物相对于相邻细胞定向其有丝分裂纺锤体。由GK蛋白相互作用结构域（GKPID）构建的分子复合物通过将微管马达蛋白连接到由外部线索定位的细胞皮层上的标记蛋白来介导不同动物分类群中的纺锤体取向。在这里，我们阐明了这种复杂的进化和征用控制主轴方向从一个更古老的机制。该复合物是通过一系列分子开发事件组装的，其中之一-GKPID结合皮质标记蛋白的能力的进化-可以通过将单个历史取代重新引入重建的祖先GKPID中来概括。这一变化揭示并重新利用了一个古老的分子表面，以前它具有完全不同的功能。我们展示了这种结合界面的物理简单性如何使一种新的蛋白质功能的进化成为许多动物生物学复杂性的关键。DOI：http://dx.doi.org/10.7554/eLife.10147.001数十亿年来，地球上的生命都是由单细胞组成的。在进化为动物的谱系中，以及在进化为植物和真菌的谱系中，多细胞生物是随着细胞开始特化并将自身排列成组织和器官而进化的。虽然多细胞生物的进化是动物生命史上最重要的事件之一，但人们对它发生的分子机制知之甚少。为了形成和维持有组织的组织，细胞必须协调它们相对于相邻细胞的位置如何分裂。这一过程的一个重要方面是有丝分裂纺锤体的方向，纺锤体是分裂细胞内的一种结构，它将染色体及其携带的遗传物质分布在子细胞之间。当纺锤体没有正确定向时，可能导致畸形组织和癌症。在各种动物中，纺锤体的方向是由一种古老的支架蛋白控制的，这种支架蛋白将纺锤体连接到细胞边缘的“标记”蛋白。安德森等人现在使用一种称为祖先蛋白质重建的技术来研究这种分子复合物是如何进化出定位纺锤体的能力的。首先，确定了支架蛋白的古老祖先的氨基酸序列，这些祖先在地球上最原始的动物起源之前就存在了。安德森等人通过计算追溯大量现代支架蛋白序列的进化，沿着生命之树追溯到遥远的过去。然后，活细胞被用来产生古老的蛋白质，从而可以通过实验来检测它们的特性。安德森等人通过实验分析支架蛋白的连续祖先版本，推断出它所锚定的分子复合物是如何控制纺锤体方向的。这种新的能力是通过一些“分子利用”事件进化而来的，这些事件将蛋白质的某些部分重新用于新的角色。支架蛋白的祖先实际上是一种酶，但其纺锤体定向能力的进化可以通过引入数亿年前发生的单个氨基酸变化来重现。一次突变怎么可能赋予如此惊人的新功能？安德森等人发现，古支架蛋白与古酶结合其靶底物分子时，使用的是其表面相同的部分来结合纺锤体定向分子标记物，而且这两种伴侣分子恰好具有某些共同的关键化学性质。两个不相关的分子之间的这种偶然的相似性为一种功能的简单进化奠定了基础，这种功能现在对多细胞动物的复杂性至关重要。DOI：http://dx.doi.org/10.7554/eLife.10147.002网站
To form and maintain organized tissues, multicellular organisms orient their mitotic spindles relative to neighboring cells. A molecular complex scaffolded by the GK protein-interaction domain (GKPID) mediates spindle orientation in diverse animal taxa by linking microtubule motor proteins to a marker protein on the cell cortex localized by external cues. Here we illuminate how this complex evolved and commandeered control of spindle orientation from a more ancient mechanism. The complex was assembled through a series of molecular exploitation events, one of which – the evolution of GKPID’s capacity to bind the cortical marker protein – can be recapitulated by reintroducing a single historical substitution into the reconstructed ancestral GKPID. This change revealed and repurposed an ancient molecular surface that previously had a radically different function. We show how the physical simplicity of this binding interface enabled the evolution of a new protein function now essential to the biological complexity of many animals. DOI: http://dx.doi.org/10.7554/eLife.10147.001 For billions of years, life on Earth was made up of single cells. In the lineage that led to animals – and independently in those that led to plants and to fungi – multicellular organisms evolved as cells began to specialize and arrange themselves into tissues and organs. Although the evolution of multicellularity is one of the most important events in the history of animal life, very little is known about the molecular mechanisms by which it took place. To form and maintain organized tissues, cells must coordinate how they divide relative to the position of their neighbours. One important aspect of this process is orientation of the mitotic spindle, a structure inside the dividing cell that distributes the chromosomes —and the genetic material they carry — between the daughter cells. When the spindle is not oriented properly, malformed tissues and cancer can result. In a diverse range of animals, the orientation of the spindle is controlled by an ancient scaffolding protein that links the spindle to “marker” proteins on the edge of the cell. Anderson et al. have now used a technique called ancestral protein reconstruction to investigate how this molecular complex evolved its ability to position the spindle. First, the amino acid sequences of the scaffolding protein’s ancient progenitors, which existed before the origin of the most primitive animals on Earth, were determined. Anderson et al. did this by computationally retracing the evolution of large numbers of present-day scaffolding protein sequences down the tree of life, into the deep past. Living cells were then made to produce the ancient proteins, allowing their properties to be experimentally examined. By experimentally dissecting successive ancestral versions of the scaffolding protein, Anderson et al. deduced how the molecular complex that it anchors came to control spindle orientation. This new ability evolved by a number of “molecular exploitation” events, which repurposed parts of the protein for new roles. The progenitor of the scaffolding protein was actually an enzyme, but the evolution of its spindle-orienting ability can be recapitulated by introducing a single amino acid change that happened many hundreds of millions of years ago. How could a single mutation have conferred such a dramatically new function? Anderson et al. found that the ancient scaffolding protein uses the same part of its surface to bind to the spindle-orienting molecular marker as the ancient enzyme used to bind to its target substrate molecule, and the two partner molecules happen to share certain key chemical properties. This fortuitous resemblance between two unrelated molecules thus set the stage for the simple evolution of a function that is now essential to the complexity of multicellular animals. DOI: http://dx.doi.org/10.7554/eLife.10147.002