bution of each mechanism to the generation of genetic Franc ¸ois Taddei, 3 Miroslav Radman, 3,7 diversity varies between species. It has been estimated and Ivan Matic 3 for Escherichia coli that, in spite of the clonal structure 1 INSERM...
morebution of each mechanism to the generation of genetic Franc ¸ois Taddei, 3 Miroslav Radman, 3,7 diversity varies between species. It has been estimated and Ivan Matic 3 for Escherichia coli that, in spite of the clonal structure 1 INSERM U 458 of its natural populations (Desjardins et al., 1995), any Ho ˆpital Robert Debre ´single nucleotide change is about 50 times more likely to 48 boulevard Se ´rurier have occurred by recombination (with a partner carrying 75935 Paris Cedex 19 such nucleotide change) than by a de novo mutation 2 Service de Syste ´matique Mole ´culaire (Guttman and Dykhuizen, 1994). The rate of successful (GDR CNRS 1005) gene transfer between bacterial populations in nature Muse ´um National d'Histoire Naturelle depends on numerous factors such as ecological isola-43 rue Cuvier tion, host range of genetic exchange vectors, activity of 75231 Paris Cedex 05 the recipient cell nucleases, DNA sequence divergence 3 INSERM E9916 between recombining molecules, type and efficiency of Faculte ´de Me ´decine Necker-Enfants Malades the recipient cell recombination machinery and, finally, Universite ´Paris V the hybrid fitness (Matic et al., 1996). Some of those 156 rue Vaugirard factors have been studied in the laboratory, but their 75730 Paris Cedex 15 impact on gene flow in nature is generally unknown. 4 INSERM U 155 Molecular mechanisms involved in the control of ho-80 rue du Ge ´ne ´ral Leclerc mologous recombination in bacteria have been exten-94276 Kremlin-Bice ˆtre sively studied. For example, it was shown that the fre-5 ACTGene Recherche et De ´veloppements quency of integration of donor DNA in the chromosome Alle ´e Christophe Colomb of recipient cells decreases exponentially with increas-Ge ´nopole ing sequence divergence between the two recombining 91035 Evry Cedex DNA molecules (Zawadzki et al., 1995; Vulic et al., 1997; France Majewski et al., 2000). The degree and pattern of DNA 6 Department of Genetics and Development divergence determine actions of the enzymes that con-Columbia University trol the outcome of recombination (Radman and Wag-College of Physicians and Surgeons ner, 1993). The initiation of recombination in bacteria New York, New York 10032 depends on the activity of the RecA protein, which is selective for sequence identity only at the initial stage of the strand exchange process (Shen and Huang, 1986). Summary Once initiated, RecA-mediated strand exchange can occur in spite of large numbers of mismatches and even Mutation and subsequent recombination events crelarge heterologies (Bianchi and Radding, 1983; Lichten ate genetic diversity, which is subjected to natural and Fox, 1984). During the strand exchange process, selection. Bacterial mismatch repair (MMR) deficient fidelity of recombination is controlled by the methylmutants, exhibiting high mutation and homeologous directed mismatch repair (MMR) system. MMR proteins recombination rates, are frequently found in natural recognize mispaired and unpaired bases in the joint populations. Therefore, we have explored the possibilheteroduplex regions and block RecA-catalyzed strand ity that MMR deficiency emerging in nature has left transfer (Worth et al., 1994). Thus, MMR is a potent some "imprint" in the sequence of bacterial genomes. inhibitor of recombination between nonidentical DNA Comparative molecular phylogeny of MMR genes from sequences (Rayssiguier et al., 1989; Shen and Huang, natural Escherichia coli isolates shows that, compared 1989; Matic et al., 1995; Vulic et al., 1997). Even low to housekeeping genes, individual functional MMR divergence is sufficient to impede recombination. For genes exhibit high sequence mosaicism derived from example, transductional recombination between two diverse phylogenetic lineages. This apparent horiserovars (Typhimurium and Typhi) of Salmonella enterzontal gene transfer correlates with hyperrecombinaica, whose genomes differ only 1%-2% at DNA setion phenotype of MMR-deficient mutators. The sequence level, is increased 10 2 -to 10 3 -fold in MMR-defiquence mosaicism of MMR genes may be a hallmark cient genetic backgrounds (Zahrt and Maloy, 1997). of a mechanism of adaptive evolution that involves MMR system is also involved in the control of replicamodulation of mutation and recombination rates by tion fidelity. Inactivation of MMR genes increases mutarecurrent losses and reacquisitions of MMR gene tion rates 10 2 -to 10 3 -fold (Glickman and Radman, 1980; functions. Schaaper and Dunn, 1987). Studies of mutation rates in natural populations of E. coli, S. enterica, and Pseudomonas aeruginosa show that MMR-deficient strains of-
