Lederberg: Genetics 



Salmonella types and of Salmonellas with one 

 another have usually failed, Baron has demon- 

 strated crosses of E. colt with a unique strain 

 of Salmonella typhimurium (3). This may be 

 especially useful as a means of developing hy- 

 brids which can be used to bridge the studies 

 of sexuality in E. colt and transduction in Sal- 

 monella. 



GENES AND VIRUSES 



Bacteria furnish a unique opportunity to 

 Study the genetic relationships with their host 

 cells. Another treasure of strain K-12 was for a 

 time hidden: it carries the temperate bacte- 

 riophage, 'k, which is technically quite favor- 

 able for genetic work. In accord with Burnet's 

 early predictions, we had anticipated that the 

 provirus for A. would behave as a genetic unit, 

 but Dr. Esther Lederberg's first crosses were 

 quite starding in their implication that the pro- 

 phage segregated as a typical chromosomal 

 marker (34). This was shown quite unambig- 

 uously by the segregation of lysogenicity versus 

 sensitivity from persistent heterozygous cells, 

 a test that bypassed the then controversial de- 

 tails of fertilization. The viabihty of such het- 

 erozygous cells supports the hypothesis that 

 lysogenicity depends in part on the develop- 

 ment of a cytoplasmic immunity to the cyto- 

 pathic effects of infecting phage as a secondary 

 result of the establishment of the prophage in a 

 bacterial chromosome. This picture is also 

 brought out by zygotic induction (26) where- 

 by the fertilization of a sensitive cell by a pro- 

 phage-bearing chromosome may provoke the 

 maturation and progressive growth of the 

 phage and the lysis of the complex. On the 

 other hand, the introduction of a sensitive 

 chromosome into a lysogenic bacterium does 

 not result in this induction. The mode of at- 

 tachment of prophage to its chromosomal site 

 is as unsettled as the general picture of the 

 higher organization of DNA, but most stu- 

 dents favor a lateral rather than an axial rela- 

 tionship for the prophage. The isolation of in- 

 tact chromosomes of bacteria would give a 

 new approach to this question but has so far 

 been inconclusive. 



Another infectious particle that has jumped 

 out of our Pandora's box determines the very 

 capacity of E. coli to function as a male partner 



in fertilization (51). For lack of a better in- 

 spiration, we call this particle "F." Two kinds 

 of male strains are now recognized according 

 to whether the F particle has a chromosomal 

 or a cytoplasmic location. F+ strains, like the 

 original K-12, are highly contagious for F and 

 will rapidly convert populations of female, F — 

 strains in which they are introduced. Hfr 

 males, on the other hand, have a chromosomal 

 localization of the F factor resulting from oc- 

 casional transpositions in F+ strains. The dif- 

 ferent localization of the F particle in the two 

 cases is diagnosed primarily by the behavior of 

 the particle in crosses. In addition, Hirota and 

 lijima (24) found that the F particle could be 

 eliminated from F+ strains by treatment with 

 acridine dyes. Hfr clones are unaffected by 

 acridine orange, but when they revert to the 

 F+ state, as occasionally happens, the F par- 

 ticle again becomes vulnerable to the dye. The 

 accessibility of extrachromosomal F is paral- 

 leled by several other examples of plasmid dis- 

 infection (reviewed in 40) ; perhaps the most 

 notable is the bleaching of green plant cells by 

 streptomycin (17, 76). No reagent is known to 

 inactivate F or prophage while bound to the 

 chromosome. 



The virus A. and the plasmagene F are analo- 

 gous in many features (28, 48). Their main 

 differences are: 



(i) Cytopathogenicity. A bacterium cannot 

 long tolerate A in its cytoplasmic slate and 

 remain viable. The vegetative A. must 

 promptly reduce itself to a chromosomal 

 state or multiply aggressively and lyse the 

 host bacterium. F has no known cyto- 

 pathic effect. 



(2) Maturation. Vegetative A, organizes a pro- 

 tein coat and matures into an infective 

 phage particle. F is known only as an 

 intracellular vegetative element; however, 

 the coat of the F+ cell may be analogous 

 to that of the phage. 



(3) Transmission. A. is infective, i.e., forms a 

 free particle which can penetrate suscepti- 

 ble cells. F is transmitted only by cell-to- 

 cell conjugation. 



(4) Fixation, A. has a foreordained site of fixa- 

 tion on the bacterial chromosome; F has 

 been identified at a variety of sites. How- 



s-72 



