Circular permutations in the molecular evolution of DNA methyltransferases

Circular permutations of genes during molecular evolution often are regarde d as elusive, although a simple model can explain these rearrangements. The model assumes that first a gene duplication of the precursor gene occurs i n such a way that both genes become fused in frame, leading to a tandem pro tein. After generation of a new start codon within the 5' part of the tande m gene and a stop at an equivalent position in the 3' part of the gene, a p rotein is encoded that represents a perfect circular permutation of the pre cursor gene product. The model is illustrated here by the molecular evoluti on of adenine-N-6 DNA methyltransferases. beta- and gamma-type enzymes of t his family can be interconverted by a single circular permutation event. In terestingly, tandem proteins, proposed as evolutionary intermediates during circular permutation, can be directly observed in the case of adenine meth yltransferases, because some enzymes belonging to type IIS, like the FokI m ethyltransferase, are built up by two fused enzymes, both of which are acti ve independently of each other. The mechanism for circular permutation illu strated here is very easy and applicable to every protein. Thus, circular p ermutation 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.