400 



CHAPTER 31 



5. It mav affect the recombination rate of 



its own or another reeomhinational 

 unit. 



Operationally, then, it is desirable to clas- 

 sify a mutation as any one or </ combination 

 oi novel, identifiable changes in the chemical 

 or physical, mutational, replicative, func- 

 tional, or reeomhinational properties of one 

 or more nucleotides. This operational defi- 

 nition of mutation includes all aspects of the 

 previous one ("a novel qualitative or quan- 

 titative change in the genetic material"). 

 Of course, at the present time, certain of the 

 changes (listed above) that identify a mu- 

 tant cannot be detected in specific individual 

 nucleotides for technical reasons. Never- 

 theless, it seems important to indicate the 

 various possible operational ways in which 

 a mutant can be identified. Subnucleotide 

 components should not be considered the 

 smallest units of the genetic material capable 

 of mutation, since the nucleotide is the small- 

 est significant chemical unit of the genetic 

 material. Since the smallest part of the 

 genetic material whose change gives rise 

 to a mutant is presumably smaller than a 

 nucleotide (and. therefore, smaller than a 

 reeomhinational unit) it is probably more 

 meaningful to speak of subnucleotide parts 

 as furnishing a number of mutational sites 

 within the nucleotide. 



The word, "novel" — used in our opera- 

 tional definition of mutation — requires some 

 additional consideration. It would have 

 been entirely correct to consider the first 

 case of segregation as being a mutation, 

 since it certainly was a novel — never before 

 recognized — change in the genetic material. 

 However, once it was found that segrega- 

 tion was not a novelty but the rule for paired 

 nuclear genes, segregation was classified as 

 a means of genetic recombination, not of 

 mutation. Similarly, genetic transformation 

 was first considered to be mutation, but after 

 further study it is more properly considered 



a mechanism for genetic recombination. 

 Consider the diseussion of Dissociation 

 whose breakages were called mutations. 

 Since more and more Dissociation-type 

 genes are being discovered, are we still justi- 

 fied in thinking the breakages they produce 

 are mutations? In the future we may con- 

 clude that such genes provide another mech- 

 anism for genetic recombination, at least 

 in certain organisms. Finally, recall that the 

 integration and deintegration of F were clas- 

 sified as genetic recombinations and not as 

 mutations. This interpretation was given in 

 the light of knowledge (but not yet pre- 

 sented) that other types of episomes are 

 known. In this case, the evolution in ter- 

 minology, from mutation to recombination, 

 was purposely shortcut. 



Since what first appears to be a novel 

 genetic change may prove, upon further in- 

 vestigation, not to be novel, we are always 

 subject to reclassifying mutation as genetic 

 recombination. Today's mutations, there- 

 fore, are possibly tomorrow's new mecha- 

 nisms for genetic recombination. 



The type of mutational change which 

 seems to be the most immune to reclassifi- 

 cation as recombination is subnucleotide 

 change. Clearly, a substitution of 5-bromo 

 uracil for thymine is a mutation, but even at 

 this level, such immunity to reclassification 

 is not absolute. Rotational substitution 

 (A:T becomes T:A) — now considered a 

 possible type of mutation — might be a nor- 

 mal mechanism of genetic recombination in 

 some organisms. 



It seems desirable, therefore, to restrict 

 the term, mutation, to describe nucleotide 

 changes which are unnatural rather than 

 novel. For this reason, we have already re- 

 frained from calling mutations certain 

 genetic changes normally part of the life 

 cycle (polyploidy in liver cells, chromosome 

 fragmentation in Ascaris), although these 

 same changes arc considered mutations when 

 they are abnormal or induced. 



