Evolution of new protein topologies through multistep gene rearrangements
Evolution of new protein topologies through multistep gene rearrangements
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DOI：
10.1038/ng1717
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发表时间：
2006-02-01
期刊：
影响因子：
30.8
通讯作者：
Tawfik, DS
中科院分区：
文献类型：
--
作者：
Peisajovich, SG;Rockah, L;Tawfik, DS
新的蛋白质折叠在整个进化过程中不断出现，但仍不清楚蛋白质折叠如何在保持其功能的同时进化，特别是当折叠变化需要几个连续的基因重排时。在这里，我们探讨了假设的进化途径连接不同的拓扑家族的DNA-甲基转移酶超家族。这些途径需要通过一系列中间体进行连续的基因重排，所有这些中间体都应该足够活跃以维持生物体的适应性。通过定向进化，从HaeIII甲基转移酶（M.HaeIII）出发，我们选择了所有在体内保持功能的中间体（一个重复的融合基因和在其5′或3′编码区部分截短的重复基因）。这些中间体导致了新的功能基因，类似于来自三个已知类别的天然甲基转移酶，或者属于我们在进化实验中首次发现并随后在天然基因组中鉴定的一类新基因。我们的研究结果表明，新的蛋白质拓扑结构可以通过多步基因重排逐渐进化，并提供有关这些过程的新见解。
New protein folds have emerged throughout evolution, but it remains unclear how a protein fold can evolve while maintaining its function, particularly when fold changes require several sequential gene rearrangements. Here, we explored hypothetical evolutionary pathways linking different topological families of the DNA-methyltransferase superfamily. These pathways entail successive gene rearrangements through a series of intermediates, all of which should be sufficiently active to maintain the organism's fitness. By means of directed evolution, and starting fromHaeIII methyltransferase (M.HaeIII), we selected all the required intermediates along these paths (a duplicated fused gene and duplicates partially truncated at their 5′ or 3′ coding regions) that maintained functionin vivo. These intermediates led to new functional genes that resembled natural methyltransferases from three known classes or that belonged to a new class first seen in our evolution experiments and subsequently identified in natural genomes. Our findings show that new protein topologies can evolve gradually through multistep gene rearrangements and provide new insights regarding these processes.