MUTATION 



In the first method we are concerned with mutants which 

 differ from the parent in being resistant to some agent which 

 inhibits or prevents growth of the original type. Here the 

 approach to the isolation of mutants can be quite direct. The 

 most elegant demonstration is of bacteriophage-resistant mutants 

 which can be recognized from the colonies they produce in 

 the areas over which a plate culture has been lysed. There 

 are a variety of types of such phage-resistant mutants, not all 

 of which are stable, but there are many which are completely 

 resistant to the phage ' producing ' them, non-lysogenic, and 

 failing to adsorb the phage in question. 



In a rather similar situation are the antibiotic-resistant 

 strains obtainable by growing the original strain in the 

 presence of antibiotic at concentrations just below that giving 

 complete sterilization. Some of the difficulties of interpreting 

 such results have already been mentioned. These need not 

 cause hesitation in accepting the mutational origin of all 

 stable resistant variants (Demerec, 1948 a, b). 



A third example of basically similar character is seen 

 when a biochemically deficient strain is studied for reversion 

 (by mutation) to wild type. A histidine-requiring strain of 

 Escherichia coli, if grown in a medium containing only a trace 

 of histidine, will give rise to histidine-independent mutants 

 which will grow readily when plated on histidine-free 

 nutrient agar. Another demonstration of the same pheno- 

 menon is obtainable by plating the deficient strain on plates 

 with minimal quantities of the critical metabolite. Colonies 

 will develop but will cease growing as the metabolite becomes 

 exhausted. In a proportion of the colonies papillae will 

 appear which can be shown to represent growth of proto- 

 trophs which have arisen by mutation in the population of 

 the developing colony. 



In the first group of methods the mutants to be isolated 

 were capable of growth on a selective medium that inhibited 

 the parent. There is, however, an important group of nutri- 

 tionally deficient mutants (auxotrophs) which fail to grow on 



