452 



ROLLIN D. HOTCHKISS 



TABLE III 



Comparison of Mutation Patterns in Spontaneous Mutants and in 



Transformations Effected by their DNA 



Properties acquired spontaneously 

 in donor strain 



Properties acquired by strain 

 transformed by donor DNA 



Ref. 



Capsule + penicillin resistance 



Capsule + streptomycin resistance 

 Capsule + nonfilamentous 



Capsule + filamentous 



Penicillin resistance (1 step) 



High penicillin resistance, (multiple 

 steps) 



High streptomycin resistance (mul- 

 tiple step type) 



High streptomycin resistance (sin- 

 gle high step type) 



Capsule, or resistance (1 step) ; very 77 



rarely, capsule -|- resistance 



Capsule, or resistance (1 step) 77 



Capsule 59, 86 



Nonfilamentous 82, 86 



Rarely, capsule + nonfilamentous 86 



Capsule 86 



Filamentous 86 



Resistance (1 step) 77 



Resistance (1 step) ; then succes- 77 



sive higher steps 



Resistance (1 step) ; then successive 65 



sive higher steps 



Resistance (1 high step) 65, 88 



thetical genes is found when the independent mutations being transferred 

 are stepwise increases in drug resistance. Penicillin resistance is known to 

 be acquired in stepwise spontaneous mutations in bacteria, each step 

 permitting growth in a higher concentration of the drug."^ When a highly- 

 resistant pneumococcal strain which has undergone multiple successive 

 steps of mutation to resistance is the source of transforming agent, peni- 

 cillin-sensitive cells are transformed only to the first, lowest level of resis- 

 tance.''^ The product of the one-step process, treated with the same DNA 

 from the multiply resistant strain, can now acquire the second step of 

 resistance, and so on. In other words, transformation has transferred in 

 stepwise fashion determinants which correspond exactly to determinants 

 which had previously been successively acquired or produced in the spon- 

 taneous mutations of the donor strain. These findings are represented 

 in Table III. The new resistant strains, like, other transformed strains, 

 can serve in turn as source of whatever DNA factors they have acquired 

 through transformiation. It is natural from these results to conclude that 

 the DNA may itself be the entity which is the original site, as well as the 

 transmissible form, of the mutation w^hich occurred in the donor strain. 



Streptomycin resistance also appears in quantitative mutational steps 

 transferred stepwise in transformation. Here we have even more striking 

 specificity of pattern, since, besides the stepwise resistance series, a still 



"1 M. Demerec, Proc. Natl. Acad. Sci. U. S. 31, 16 (1945). 



