8 MUTATIONS 



you have the population in a steady state, the number of mutant cells 

 added will correspond just to the number of mutations. Does this 

 require any explanation or is it obvious? 



Lederberg: Why number of mutant cells rather than proportion, 

 Kim? 



Atwood: Well, the total number of cells stays constant in the steady 

 state, so it's the same thing. 



M 



Lederberg: Oh, no! The proportion is always — ■, that is, the number 



of mutant cells over the total number of cells. 



Atwood: You are right, it is this ratio. 



Lederberg: I see the point now. How do you calculate n? During the 

 chromosomal phase, n is "log" M, but n during the stable phase is 

 some complement of N. 



Atwood: Yes. 



Goldstein: May I put something in here, because it is going to come 

 up the day after tomorrow again? What we really have to know is the 

 probability that a given cell will be a mutant, so I am not concerned 

 with total numbers of mutants at all. The problem is, given a sperm 

 cell at some time, what is the probability that it will be a mutant? 

 Or, given a cell in a germ line, what is the probability that it will be 

 a mutant? If you make a diagram of a clone, starting with the zygote 

 (Fig. 2), there is a period that you have been talking about in embry- 

 onic life when you have this kind of clonal multiplication. Then, 

 there is a period later on when you have a stem cell mechanism, with 

 each division leading to a clone of sperm and to another stem cell. 



The point that I would like to make here is that this entire se- 

 quence from zygote to sperm, throughout life, is really a single clone. 

 If you look at any clonal diagram, the cells along one edge of the 

 diagram are always sending off subclones. The cells along one edge 

 (and elsewhere) can therefore represent lines of stem cells, as in Figure 

 2, and the derivative subclones will represent the spermatogonia, 

 spermatocytes, and spermatids of the successive sperm clones derived 

 from that stem line. Consequently, the real difference between the 

 embryonic period and the later one is the difference in interdivision 

 interval that we have been talking about. In the former, the interval is 

 very small; in the stem cell line, presumably, the interval is much 

 greater. 



Atwood: When you get a stem line that is mutant, it will simply 

 continue to be mutant, and from then on, every clone that it gives off 

 will produce mutant gametes. 



Goldstein: Yes. If you will let me define the probability that I am 



