title: Transposon-mediated adaptive and directed mutations and their potential evolutionary benefits.
abstract: Transposons, mobile genetic elements that can hop from one chromosomal location to another, are known to be both beneficial and deleterious to the cell that bears them. Their value in accelerating evolutionary adaptation is well recognized. We herein summarize published research dealing with these elements and then move on to review our own research efforts which focus on a small transposon that can induce mutations under the control of host factors in a process that phenotypically and mechanistically conforms to the definition of 'directed mutation'. Directed mutations occur at higher frequencies when they are beneficial, being induced by the stress condition that they relieve. Here, we review evidence for transposon-mediated directed mutation in Escherichia coli. Deletion mutants in the crp gene can not grow on glycerol (Glp(-)); however, these cells mutate specifically to efficient glycerol utilization (Glp(+)) at rates that are greatly enhanced by the presence of glycerol or the loss of the glycerol repressor (GlpR). These rates are greatly depressed by glucose or by glpR overexpression. Of the four tandem GlpR-binding sites (O1-O4) in the control region of the glpFK operon, O4 (downstream) specifically controls glpFK expression while O1 (upstream) controls mutation rate. Mutation is due to insertion of the small transposon IS5 into a specific site just upstream of the glpFK promoter. Mutational control by the glycerol regulon repressor GlpR is independent of the selection and assay procedures, and IS5 insertion into other gene activation sites is unaffected by the presence of glycerol or the loss of GlpR. The results establish the principle of transposon-mediated directed mutation, identify a protein responsible for its regulation, and define essential aspects of the mechanism.
authors.affiliation: Division of Biological Sciences, Department of Molecular Biology, University of California at San Diego, La Jolla, CA, USA. msaier@ucsd.edu
authors.forename: Zhongge
authors.initials: Z
authors.lastname: Zhang
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D000220:Adaptation, Biological; D004251:DNA Transposable Elements; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005990:Glycerol / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D016254:Mutagenesis, Insertional
chemical_list: D004251:DNA Transposable Elements; D005990:Glycerol