226 ROBERT L. SINSHEIMER 



that the likelihood of mutagenesis must be strongly dependent, not only 

 upon the particular mutagen, but upon the nature of the nucleotide se- 

 quence at neighboring sites along the DNA molecule. The influence of 

 neighboring nucleotides must extend for more than one nucleotide pair. 



d. Host-Controlled Variation of Bacteriophage 



In general the progeny of bacterial virus infection, excepting the rela- 

 tively rare mutants, has the same phenotypic and genotypic properties 

 as its parents, regardless of the species of host bacterium employed. 

 However, it has been observed that in certain instances, growth on a 

 particular bacterial host will result in progeny with at least one different 

 property from those of the parents. Repeated culture of the phage on the 

 particular host preserves this property among the progeny, but passage 

 through another host will cause a reversion of the phage culture to its 

 original character. Thus, the altered characteristic of the modified phage 

 does not appear to be the result of a permanent mutation of the geno- 

 type but is a variation induced by passage through a particular host and 

 only maintained by passage through that host. 166 



The only host-controlled character which has been studied in this way 

 is that of host range, although there is no reason to believe other properties 

 cannot be modified in this manner. Passage through a particular host may 

 enlarge or restrict the host range of the progeny phage. 



Thus phage T2 normally infects with an equal efficiency, E. coli B, Shiqella dysen- 

 teriae, and a mutant of E. coli B, E. coli B/4 . However, the progeny of growth on 

 E. coli B/4 infect with full efficiency only the S. dysenteriae. With E. coli B or E. coli 

 B/4o, only one cell in a thousand can be infected by this progeny. 167 A variety of 

 experiments have indicated that the phage population is homogeneous and that it is 

 only an exceptional cell that can be infected. 166 However, passage of the progeny 

 from E. coli B/4 through S. dysenteriae or through the small fraction of E. coli B 

 cells that will support their growth, results in a second generation progeny with the 

 original ability to infect all three hosts. Only by repeated culture on the small frac- 

 tion of E. coli B/4o cells that will support their growth can the restricted host range 

 be maintained. 



The modified phage particles adsorb to the resistant cells and kill them 

 but no infective phage are ever found. The nature of the block to devel- 

 opment is unknown but as it does not appear to involve the external 

 features of the phage, the DNA or the internal protein appear to be im- 

 plicated. Similar phenomena, more often involving an extension of host 

 range, have been observed with phage Tl and with the temperate phages 

 X, P2, and P22. 7 



166 S. E. Luria, Cold Spring Harbor Symposia Quant. Biol. 18, 237 (1953). 



167 S. E. Luria and M. L. Human, /. Bacteriol. 64, 557 (1952). 



