PROBLEMS OF MEASUREMENT OF MUTATION RATES 



9 



Figure 2. Clone diagram, modified to show stem cell mechanism. The model 

 depicts formation of 4 stem cell lines (heavy lines) each giving rise to subclones 

 (light lines) yielding 4 sperm each (open circles). The diagram emphasizes that 

 the stem cell mechanism is not formally different from ordinary clonal growth. 

 The main differences are (1) that some lines within the clone terminate while 

 others go on, and (2) that the interdivision times may differ between lines within 

 the clone (e.g., the broken lines, hght lines, and heavy lines shown here). See 

 also Fig. 25, p. 179. 



talking about, it may clarify the thing. Let's take the end result, a 

 sperm, and ask what is the probability that that sperm will be mutant? 

 If we are dealing with a single clone, where all the interdivision times 

 are equal, we could express that probability simply as the probability 

 per cell division times the total number of cell divisions in the origin 

 of that particular sperm. 



What I am maintaining is that the only thing that has to be added 

 to this simple formula is that the interdivision time is different in differ- 

 ent parts of the clonal diagram. If you knew for any sperm, say at 

 age 30, by how many divisions that sperm was removed from the 

 zygote, and assuming a constant mutation probability per cell cycle, 

 you could easily calculate the probability that this sperm would be 

 mutant. 



Steinberg: Shouldn't that equation be modified slightly? The prob- 



