The Genetic Control of Mutation 



389 



3. All patients 8 with clinical measles 

 (rubeola) have a high incidence of chromo- 

 some breakage in the white blood cells by the 

 fifth day after onset of the rash. Chromo- 

 some breaks occur in 33 to 72% of the cells 

 examined, and all chromosomes are break- 

 able at numerous positions, although the 

 unions between ends produced by breakage 

 resulting in structural rearrangements are of 

 low frequency. 



4. After infection of human cell lines in 

 vitro with the simian virus SV. 1( ,, large num- 

 bers of chromosomal mutants are detected ' 

 including chromosome loss, chromosome 

 breakage, and gross rearrangements like di- 

 centrics, rings, and (probably) transloca- 

 tions. The frequency with which these in- 



,; Studied by W. W. Nichols, A. Levari, B. Hall. 



and G. Ostergren (1962). 



7 See P. S. Moorhead and E. Saksella (1963). 



volve different chromosomes is apparently 

 not random. At least seven other viral in- 

 fections in man are associated with an in- 

 creased incidence of various chromosomal 

 rearrangements in white blood cells. 



We do not know whether these effects are 

 due to a general metabolic effect of the pres- 

 ence, functioning, or replication of viral 

 nucleic acids; to a specific episomal-like fea- 

 ture of these viruses; or to some other fac- 

 tor or combination of factors. In any case, 

 viruses can induce mutations in cells of higher 

 organisms in vivo and in vitro, and it is pos- 

 sible that normally-present extranuclear 

 genes can also do so. Clearly then, the 

 genetic control of mutability involves extra- 

 nuclear genes, episomes, and ordinary chro- 

 mosomal genes; each is hypothetically ca- 

 pable of affecting its own mutability as well 

 as each other's. 



SUMMARY AND CONCLUSIONS 



The spontaneous occurrence of genomic and of single, whole-chromosome mutations 

 is suppressed by the genotypic control of the processes of mitosis and meiosis. Struc- 

 tural rearrangements in chromosomes are suppressed by the precision of synapsis and 

 crossing over. Such controls are possible because of the linear arrangement of genes 

 in the chromosomes. In certain cases involving the production of polyploid and poly- 

 nemic chromosomes and several monocentric chromosomes from a polycentric chro- 

 mosome, genetic change is genotypically regulated. 



Point-mutation frequencies also are regulated genotypically, as shown by the general 

 control of mutation response to temperature changes or to mutagenic agents; by the 

 occurrence of mutator genes; and by genes which produce chromosome breakages that 

 can lead to losses, shifts, and transpositions and, therefore, position effects. Regulator 

 genes control the operation of genes that cause breakages or other mutations. Trans- 

 ducing phages induce point mutations; viruses that attack higher animals can also 

 effect chromosomal breakage. 



REFERENCES 



Demerec, M., "Selfer Mutants of Salmonella typhimurium" Genetics. 48:1519-1531, 

 1963. 



Magni, G. E.. "The Origin of Spontaneous Mutations During Meiosis." Proc. Nat. 

 Acad. Sci., U.S., 50:975-980, 1963. 



McClintock, B., "The Origin and Behavior of Mutable Loci in Maize," Proc. Nat. 

 Acad. Sci., U.S., 36:344-355, 1950. Reprinted in Classic Papers in Genetics, 

 Peters, J. A. (Ed.), Englewood Cliffs. N.J.: Prentice-Hall. 1959, pp. 199-209. 



