STEPHENS: RESUME OF THE SYMPOSIUM 499 



sequence is the cistron or functional gene. Within a cistron muta- 

 tion is due to the deletion, duplication, or re-arrangement of base 

 pairs. All such changes alter spatial configuration within the cis- 

 tron, and hence modify its coding system. At this level of organ- 

 ization the concept of "point mutation" is meaningless, e.g., as far as 

 we know an adenine base cannot mutate into a modified form of 

 adenine and remain permanently incorporated in the system. All 

 mutations within a cistron, i.e., intra-genic mutations, involve a 

 change in the order of its separable base pairs. Theoretically, extra- 

 genic mutations would involve deletions, duplications, or re-arrange- 

 ments of whole cistrons without disturbing their internal struc- 

 tures. It is not clear whether intra- and extra-genic mutations would 

 result from different mechanisms or whether it would be possible 

 always to discriminate between them. Neither is it clear whether 

 the cistrons are serially discrete or overlapping. 



If we try to extrapolate from the nucleotide level to the chro- 

 mosomal level in higher organisms, we run into semantic difficulties. 

 Here the criterion of separability (recombination) is applied to dis- 

 tinguish "extra-genic" from "intra-genic" events, and the latter 

 are assumed to be true "point mutations". But we have seen at 

 the nucleotide level that "point mutations" probably do not exist 

 and that separability is no valid criterion for distinguishing between 

 extra- and intragenic mutation. Separability is not only an invalid 

 criterion, it suffers from the disadvantage that the answer obtained 

 varies with the sensitivity of the test. This is well illustrated by the 

 interesting case of the A complex in maize whose recent experimental 

 history has been presented by Laughnan. Earlier work, commenced 

 by Stadler and developed independently by Laughnan, had shown 

 that the A complex was separable into alpha and beta elements 

 which could be considered tandem serial repeats. By setting up 

 test-crosses with appropriately marked chromosomes, it could 

 be shown that certain mutant events in the A complex were always 

 associated with crossing over, while others were not. Separa- 

 bility, therefore, became the criterion for distinguishing "extra- 

 genic" sheep from "intra-genic" goats. Later, a more rigorous exam- 

 ination of the "intra-genic" mutants by Laughnan has shown that 

 they do not meet the specifications of true "point mutations" but 

 can best be explained by physical losses of alpha and beta elements. 



