16 MUTATIONS 



Lederberg: Then, it is a rate per what, if it is a rate? 



Atwood: It is a rate per human generation, including all the ages 

 involved. Usually such data are not numerous enough to form age 

 groups, so they are all lumped. In the cases we just talked about, two 

 age groups were formed and compared. 



Magni: I want to mention that Cavalli-Sforza (6) in our Depart- 

 ment is trying to estimate the age dependence of mutations in man 

 by means of a new method. He is studying the dependence of the sex 

 ratio of the progeny of a woman, on the age of her father at the time 

 of her birth. He has so far data on a sample of about 200,000 Italians 

 and is trying to include the proper question in the census which will 

 be made in Italy in two years. This would yield data on fifty million 

 inhabitants, from which he will be able to have a very precise estimate 

 of the age dependence. 



Atwood: Well, if this sort of method shows an age dependence, 

 you might infer something about the sex dependence of the mutation 

 rate. If, for example, the hemophilia rate is related to maternal grand- 

 father's age, then it could be argued that the mutant frequency from 

 females is never higher than the apparent mutant frequency at zero 

 age by extrapolation in males. 



Now, I wanted to show what slight evidence I have been able to 

 gather about how we should regard the contribution of embryonic 

 period versus stem cell period. This is with respect to two things, both 

 not conclusive but suggestive of a higher mutation rate in early de- 

 velopment. One is the origination of red cell variants with respect to 

 ABO phenotype, and the other is the origination of pigment phenotype 

 sectors in mussel shells. 



Magni: Before you enter into details on ABO antigens, Atwood, 

 I would like to mention one point which might be of interest for the 

 previous general discussion. 



All that you have said needs an assumption which, for the time 

 being, has not yet been proved true, i.e., that mutation rate per cell 

 per generation is the same in mitosis and meiosis. During the develop- 

 ment of germ line in the embryonic period and in the stem line 

 period only mitotic divisions occur, but from the time of sexual 

 maturity, meiotic divisions from the stem line are responsible for 

 the production of mature spermatozoa. If the mutation rate per cell 

 per generation is higher in meiosis than in mitosis, this will certainly 

 affect the apparent over-all mutation frequency. 



Lederberg: It would not be dependent on age. 



Magni: Well, there will be no clear expectation for age dependence. 



