Werner Arber - Selected Major Publications #

Biozentrum, University of Basel (Switzerland)

1) Arber, W., Kellenberger, G. & Weigle, J. (1957) La défectuosité du phage Lambda transducteur. Schweiz. Z. Path. Bakt. 20, 659-665

Arber, W., Kellenberger, G. & Weigle, J. (1960). The defectiveness of Lambda transducing phage. In: E.A. Adelberg (ed.) Papers on bacterial genetics. Little, Brown & Co., Boston-Toronto, pp. 224-229

2) Arber, W. (1960) Transduction of chromosomal genes and episomes in Escherichia coli. Virology 11, 273-288

3a) Arber, W. & Dussoix, D. (1962) Host specificity of DNA produced by Escherichia coli. I. Host controlled modification of bacteriophage . J. Mol. Biol. 5, 18-36

3b) Dussoix, D. & Arber, W. (1962) Host specificity of DNA produced by Escherichia coli. II. Control over acceptance of DNA from infecting phage . J. Mol. Biol. 5, 37-49

4) Arber, W. (1965) Host-controlled modification of bacteriophage. Annu. Rev. Microbiol. 19, 365-378

5) Arber, W. & Linn , S. (1969) DNA modification and restriction. Annu. Rev. Biochem. 38, 467-500

6) Arber, W., Iida, S., Jütte, H., Caspers, P., Meyer, J. & Hänni, C. (1979) Rearrangements of genetic material in Escherichia coli as observed on the bacteriophage P1 plasmid. Cold Spring Harbor Symp. Quant. Biol. 43, 1197-1208

7) Sengstag, C. & Arber, W. (1983) IS2 insertion is a major cause of spontaneous mutagenesis of the bacteriophage P1: non-random distribution of target sites. EMBO J. 2, 67-71

8) Iida, S., Meyer, J. & Arber, W. (1983) Prokaryotic IS elements. In: J. Shapiro (ed.) Mobile Genetic Elements. Academic Press, N.Y., pp. 159-221

9) Olasz, F., Stalder, R. & Arber, W. (1993) Formation of the tandem repeat (IS30)2 and its role in IS30-mediated transpositional DNA rearrangements. Mol. Gen. Genet. 239, 177-187

10) Naas, T., Blot, M., Fitch, W.M. & Arber, W. (1994) Insertion sequence-related genetic variation in resting Escherichia coli K-12. Genetics 136, 721-730

11) Arber, W. (1995) The generation of variation in bacterial genomes. J. Mol. Evol. 40, 7-12

12a) Arber, W. (2000) Genetic variation: molecular mechanisms and impact on microbial evolution. FEMS Microbiol. Rev. 24, 1-7

12b) Arber, W. (2002) Evolution of prokaryotic genomes. In: Current Topics in Microbiology and Immunology, Vol. 264/I, Pathogenicity Islands and the Evolution of Pathogenic Microbes. (J. Hacker & J.B. Kaper, eds.) pp. 1-14


Publication 1 was first published in French in a non-refereed Swiss journal with unknown availability in foreign countries. Three years later, it was translated into English by the editor publishing a collection of classical papers on bacterial genetics. This paper is a summary of W. Arber’s Ph.D. Thesis and it shows that the specialized transducing phage gal has a hybrid genome consisting of both viral and some bacterial genes (those responsible for the fermentation of galactose). The acquisition of bacterial genes is compensated by the deletion of some of the genes essential for viral reproduction. This lack of activity can be complemented by wild-type helper viruses coinfecting together with gal. The notion of inserting foreign genes in an autonomously replicating DNA molecule (vector) served in the early 1970s for the development of the recombinant DNA technology.

Article 2 reports on research done by W. Arber during his postdoctoral training at the University of Southern California in Los Angeles. It shows that viruses can not only transduce chromosomal genes but also autonomously replicating plasmids such as the conjugative plasmid F.

Articles 1 and 2 are basic contributions to the natural process of horizontal DNA transfer, also called gene acquisition.

3. The two simultaneously published articles 3a) and 3b) laid the basis for the understanding of host controlled modification. The articles show that it is the viral DNA rather than any other component which becomes strain-specifically modified by passing through a host, although modification is not an inheritable trait. It is also shown that not properly modified viral DNA is rejected by nucleolytic cleavage upon infection of a different, restricting host strain.

4. This is the first general summary on the knowledge of DNA restriction and modification and it already includes evidence that modification is brought about by post-replicative methylation of some specifically located bases. The phenomenon of restriction and modification is not limited to bacteriophage DNA; it also affects the bacterial chromosome and plasmids. The review also refers to possible applications of restriction enzymes, including DNA sequence analysis.

5. This review refers to the state of the art at a time when the first in vivo restriction activities had been demonstrated and good evidence for sequence-specific DNA methylation had become available. This led the authors to a discussion of possible structures of recognition sites and of evolutionary relatedness of restriction-modification systems of different specificities.

6. In this article, experiments on investigations of genetic instability are presented at an annual symposium on quantitative biology in Cold Spring Harbor. The observed DNA rearrangements relate mainly to transposition activities of mobile genetic elements resident in the E. coli chromosome, its plasmids and viruses.

7. This research article clearly shows that the mobile genetic element IS2 carried in E. coli is a main responsible for spontaneous lethal mutagenesis of the bacteriophage P1; it also shows that the chosen target sites are non-randomly distributed but do not consist of homologous sequences. Furthermore, this paper applies an interesting strategy by using mutations accumulated in the prophage state and thus allowing one to study molecular mechanisms of the formation of lethal mutations.

8. This is a presentation of the knowledge available in the early 1980s on the bacterial IS elements. The article written by the three senior scientists of Arber’s group represents a thoroughly reflected overview and contains a number of suggestive conclusions based on experimental data.

9. Investigations carried out with IS30 led to the formulation of a transposition model of IS30 going through an unstable state of joined dimers of the IS30 element. The interesting aspect of this model is the prediction of bursts of transposition, i.e. that subclones of bacteria carrying IS30 may become genetically unstable and undergo genomic rearrangements at relatively high frequencies. The article also suggests that many of the rearrangements lead back to a parent-like, genetically stable situation insuring a long-term maintenance of the involved strains.

10. In this article, bacteria having rested at room temperature for as long as 30 years were investigated by a restriction fragment length polymorphism study which revealed that several residential IS elements mediate transpositional DNA rearrangements not only in the phase of growth, but also in the resting phase. These investigations also revealed bursts of IS30 transposition which can be explained by the model presented in article 9.

11. This overview on the generation of variation in bacterial genomes draws a general picture of the different molecular mechanisms of spontaneous mutagenesis in bacteria and it postulates that many specific enzymes and enzyme systems which are encoded for in the bacterial chromosome and/or on plasmids and viral genomes are responsible for the generation of genetic variations or for the limitation of such variation to tolerable but evolutionarily useful frequencies. The relevant genetic determinants are postulated to primarily fulfill evolutionary functions and to have also been selected for this purpose.

12. On the basis of established knowledge of microbial genetics one can distinguish three major natural strategies in the spontaneous generation of genetic variations in bacteria. These strategies are: (1) small local changes in the nucleotide sequence of the genome, (2) intragenomic reshuffling of segments of genomic sequences and (3) the acquisition of DNA sequences from another organism. The three general strategies differ in the quality of their contribution to microbial evolution. Besides a number of non-genetic factors, various specific gene products are involved in the generation of genetic variation and in the modulation of the frequency of genetic variation. The underlying genes are called evolution genes. They act for the benefit of the biological evolution of populations as opposed to the action of housekeeping genes and accessory genes which are for the benefit of individuals. Examples of evolution genes acting as variation generators are found in the transposition of mobile genetic elements and in so-called site-specific recombination systems. DNA repair systems and restriction-modification systems are examples of modulators of the frequency of genetic variation. The involvement of bacterial viruses and of plasmids in DNA reshuffling and in horizontal gene transfer is a hint for their evolutionary functions. Evolution genes are thought to undergo biological evolution themselves, but natural selection for their functions is indirect, at the level of populations, and is called second-order selection. In spite of an involvement of gene products in the generation of genetic variations, evolution genes do not programmatically direct evolution towards a specific goal. Rather, a steady interplay between natural selection and mixed populations of genetic variants gives microbial evolution its direction.

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