Circular permutations in the molecular evolution of DNA methyltransferases
Circular permutations in the molecular evolution of DNA methyltransferases
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DOI：
10.1007/pl00006529
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发表时间：
1999-07-01
影响因子：
3.9
通讯作者：
Jeltsch, A
中科院分区：
文献类型：
--
作者：
Jeltsch, A
分子进化过程中基因的循环排列通常被认为是难以捉摸的，尽管一个简单的模型可以解释这些重排。该模型假设，首先，前体基因的基因复制发生在这样一种方式上，即两个基因在框架内融合，导致串联蛋白。在串联基因的5‘部分产生新的起始密码子并在基因的3’部分的对等位置终止后，编码的蛋白质代表前体基因产物的完美循环排列。以腺嘌呤-N-6DNA甲基转移酶的分子进化为例说明了该模型。该家族的β-和伽马类型的酶可以通过单个循环排列事件进行相互转化。有趣的是，在环状排列过程中被认为是进化中间产物的串联蛋白，可以在腺嘌呤甲基转移酶的情况下直接观察到，因为一些属于IIS类型的酶，如FokI甲基转移酶，是由两种融合的酶组成的，这两种酶都是相互独立的活性。这里说明的循环排列的机制非常简单，适用于每种蛋白质。因此，循环排列可以被认为是分子进化中的一个正常过程，不应将保守氨基酸基序的改变解释为反对发散进化。
Circular permutations of genes during molecular evolution often are regarded as elusive, although a simple model can explain these rearrangements. The model assumes that first a gene duplication of the precursor gene occurs in such a way that both genes become fused in frame, leading to a tandem protein. After generation of a new start codon within the 5' part of the tandem gene and a stop at an equivalent position in the 3' part of the gene, a protein is encoded that represents a perfect circular permutation of the precursor gene product. The model is illustrated here by the molecular evolution of adenine-N-6 DNA methyltransferases. beta- and gamma-type enzymes of this family can be interconverted by a single circular permutation event. Interestingly, tandem proteins, proposed as evolutionary intermediates during circular permutation, can be directly observed in the case of adenine methyltransferases, because some enzymes belonging to type IIS, like the FokI methyltransferase, are built up by two fused enzymes, both of which are active independently of each other. The mechanism for circular permutation illustrated here is very easy and applicable to every protein. Thus, circular permutation can be regarded as a normal process in molecular evolution and a changed order of conserved amino acid motifs should not be interpreted to argue against divergent evolution.