title: Evolution of new protein topologies through multistep gene rearrangements.
abstract: 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 from HaeIII 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 function in 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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100 Israel.
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Peisajovich
authors.forename: Liat
authors.initials: L
authors.lastname: Rockah
authors.forename: Dan S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D000595:Amino Acid Sequence; D015257:DNA-Cytosine Methylases / Q000737:chemistry / Q000235:genetics; D019020:Directed Molecular Evolution; D019143:Evolution, Molecular; D020440:Gene Duplication; D015321:Gene Rearrangement / Q000235:genetics*; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation / Q000235:genetics; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment
chemical_list: D011506:Proteins; D011993:Recombinant Fusion Proteins; D015257:DNA-Cytosine Methylases; C027823:Cytosine 5-methyltransferase