Penicillin-induced Penicillin Resistance 95 



mutations result in minute qualitative alterations (minor 

 changes in folding of the molecule or displacement of a single 

 amino acid within the chain) too slight to be detected by most 

 available techniques? If this is so, perhaps a series of successive 

 mutations and alterations to the protein molecule may be 

 necessary before the change is detectable. Or, perhaps, a 

 single mutation may never result in more than a relatively 

 slight shift in the distribution of properties amongst a micro- 

 heterogeneous population of very closely related but different 

 individual molecules within a molecular species, all of which 

 have a similar function [see Colvin, Smith and Cook (1954), 

 for evidence of " microheterogeneity " amongst populations of 

 a single species of protein molecules]. The slow evolution, 

 from cultures of penicillin-sensitive staphylococci, grown for 

 very long periods in low penicillin concentrations, of strains 

 apparently capable of producing minute traces of penicil- 

 linase (Barber, this symposium, p. 262) is of special interest 

 in this connexion. Naturally occurring qualitative evolution 

 at a molecular level may proceed very much more slowly 

 than might be at first suspected from consideration of the 

 mutation rates and selection pressures observed within the 

 laboratory. 



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