450 



CHAPTER 49 



case, the evolution in terminology, from mu- 

 tation to recombination, was purposely short- 

 circuited. 



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. Under these circumstances, 

 today's mutations are possibly tomorrow's 

 new mechanisms for genetic recombination. 



The type of mutational change which 

 seems to be most immune to reclassification 

 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, may be found to be a 

 normal mechanism of genetic recombination 

 in some organisms. 



It seems desirable to restrict the term muta- 

 tion to describe nucleotide changes which are 

 unnatural rather than novel. You may re- 

 call that we have already refrained from call- 

 ing mutations certain genetic changes which 

 occur naturally in the life cycle (polyploidy 

 in liver cells, chromosome elimination in 

 Sciara), although these same changes can 

 be considered mutations at least when in- 

 duced by extra-organismal factors. 



What have we learned about recombina- 

 tion, the operation we used first to investi- 

 gate the genetic material? We have found a 

 variety of mechanisms which result in new 

 genetic combinations, that is, changes in 

 position or amount of naturally occurring 

 nucleotide material. For chromosomal 

 genes, these mechanisms include segregation, 

 independent segregation, nondisjunction, 

 crossing over, fertilization, polyploidy, poly- 

 teny, aneusomy, structural changes in chro- 

 mosomes caused by breakage (such as 

 deletion, duplication, inversion, transloca- 

 tion, transposition, and shift), transforma- 

 tion, transduction, and strand recombina- 



tion in vitro. For extranuclear genes, we 

 have found recombination to involve varia- 

 tion in number or kind of these genes; for 

 episomes, we have the same recombinations 

 as for extranuclear genes plus the pairing of 

 episomes with, or their integration in, the 

 chromosome. 



In cases of transformation, strand recom- 

 bination in vitro, and phage or plant virus 

 infection, genetic recombination may re- 

 quire the addition or presence only of DNA 

 or RNA. In most cases, however, it is not 

 possible to make such a direct association, 

 since, at the time of genetic recombination, 

 the nucleic acid is apparently bound to pro- 

 tein in the form of nucleoprotein. Thus, for 

 example, we cannot attribute chromosome 

 breakage or crossing over to an action on or 

 by DNA alone. It should also be reahzed 

 that mutation (with the exception of certain 

 virus-induced mutations) and template usage 

 for gene action probably occur when the 

 nucleic acid is in the form of nucleoprotein. 

 For example, while the information may be 

 carried solely by genetic RNA or DNA, this 

 information is probably often used while the 

 nucleic acid is bound to protein. Accord- 

 ingly, our understanding of the usual recon 

 and cistron will have to be expressed in terms 

 of nucleoprotein activity, until such time as 

 special materials and techniques are avail- 

 able. 



Finally, you will realize that this book has 

 been restricted largely to those consequences 

 of genes which may reveal something of the 

 nature of the genetic material. In compari- 

 son with what is known, very little has been 

 said about the applications of genetic princi- 

 ples. We have had some brief discussions of 

 how genetics plays a central role in our 

 understanding of biological evolution, of 

 diff'erentiation, and of development. We 

 have mentioned briefly some of the uses of 

 genetics in plant and animal breeding, and 

 in the understanding of inborn and infectious 

 diseases. Some discussion of the past, pres- 



