76 Discussion 



cells, which express their defect on the first division, are due to something 

 analogous to a lethal nuclear mutation, then this change must either 

 have occurred simultaneously in two adjacent nuclei of the initial cell, 

 or else in one nucleus one generation back. In a scheme of this sort, 

 under conditions such as Dr. Hughes used where the behaviour of cells 

 in a population which had been carried through several generations was 

 studied, one would expect to find a number of non- viable cells which 

 failed to divide ab initio, as well as cells which segregated a non-viable cell 

 only at the second generation. What is your opinion on this, Dr. Hughes? 



Hughes: I don't know what happens inside the cell. But the type 

 which gives one lethal and one normal cell exists, and so does the one 

 that is immediately a lethal. On the first isolate we have 3 per cent of 

 this lethal, and 12 per cent of a cell that divides to give one lethal and 

 one normal; on re-selection from these we get up to 17 per cent direct 

 lethals and 57 per cent of mixed ones. At no time did I see this second 

 generation type you anticipate. It was first division or nothing. I don't 

 know the explanation. 



Hayes: Stress has been laid on the fact that these changes are probably 

 either mutational, or else have something to do with enzymic equilibria 

 and so on in the cytoplasm. 



There is another kind of genie change which could have profound 

 effects on the cell, which is not mutational in the sense of altering the 

 direct function of a particular gene, and which is not connected with the 

 cytoplasm, and this is the question of the rearrangement of genes within 

 the chromosome, the position effect. It has been shown recently by 

 Jacob, at the Pasteur Institute, that when selection is made for Hfr 

 derivatives of Esch. coli K 12 donor strains, which have a very high 

 fertility, the genes of different Hfr isolates from the same witd-type 

 strain may appear in quite different orders on the chromosome. It is 

 not known whether the change to the Hfr state is directly associated 

 with, and possibly due to, rather rare chromosomal rearrangements, or 

 whether the rather rare Hfr mutations selected for are simply super- 

 imposed upon chromosomal reorganizations which may occur quite 

 frequently. There is some vague morphological evidence of nuclear 

 fusion, suggestive of autogamy, in bacterial cells ; such a process could 

 possibly result in rearrangement of the order of genes on the chromo- 

 somes when they separate out again. Position effects of that sort might 

 greatly influence the viability or the biological efficiency of individual 

 bacterial cells. 



Hughes: I should mention that Avhile you can select out for a high 

 proportion of lethals, you cannot select out a lethal-free strain. You can 

 get rid of the cells which die immediately, you can get the percentage 

 down to a fraction of one per cent, but you cannot lose entirely the cells 

 which divide into one lethal and one normal. They persisted however 

 long I have gone on with this type of experiment. 



Lederberg: Do I understand correctly that these lethal-type cells only 

 appear during the zero or first generation of transfer from broth or agar 

 and not subsequently in the growth of the clone ? 



Hughes: That is correct as far as I know. 



