MUTATIONS 



Zamenhof: But all this applies to spontaneous mutations. Of course, 

 in the case of induced mutations, very frequently, the concept of rate 

 does not apply at all (43) . Will that be discussed later? 



Atwood: We can discuss that later. Another factor involved here 

 is simply time. If you consider mutation as constant per time unit 

 rather than per cell division then the reported rate, uncorrected for 

 this, would already have about a factor of 10^ difference, because you 

 have microbial rates being measured in units close to hours, and human 

 rates per generation, about 3 X 10^ hours. 



Novick: What is the time in the human between successive genera- 

 tions of the spermatogonia? 



Atwood: I don't know, but what I meant to say was that the rates 

 are expressed per human generation, not cell generation. In human 

 rate measurements, the individual is assumed to be merely a pair of 

 alleles, and nothing is assumed about cell divisions. 



Benzer: But gametes are the result of a large clonal development, 

 during which mutations occur. Is that part of your argument? 



Atwood: Yes, that is what I want to get into. Now we can attempt 

 to reconstruct what has gone on between generations, between the time 

 the mutation rate would be measured in one generation and in the 

 next. We have a cell population which will end up as gametes 

 and, for a time, this cell population increases like a culture of micro- 

 organisms; that is, with clonal growth. Then it reaches a steady state, 

 in which the population size remains about the same, and you have 

 a stem line regime with the gametes being the overflow. 



Auerbach: This is for the male only, this diagram, isn't it? 



Atwood: Well, yes; it is probably a little different for the female, 

 since oocytes would not be dividing. 



Russell: There is actually a steady drop in numbers in the female, 

 owing to degeneration of oocytes as well as to ovulation. But this prob- 

 ably has no bearing on what you have in mind. 



Atwood: In fact, it is even unimportant that there are any females 

 for this argument. If the mutations occur only in males, our estimate 

 based on the entire population would be wrong by only a factor of 2. 

 There is some evidence that human mutation rates are higher in males. 

 This is being argued. Do you want to say anything about it now, Jim? 



Neel: I think that Kim is referring to Haldane's 1947 paper (16) on 

 hemophilia. There the basis for the argument is a test for the carrier 

 state in females which is now felt to be highly unreliable. I am afraid 

 that while the methodology in that paper is sound, the laboratory pro- 

 cedures on which Haldane based his arguments are very questionable. 



