DELAYED PHENOTYPIC EXPRESSION OF SPONTANEOUS 

 MUTATIONS IN ESCHERICHIA COLI* 



HOWARD B. NEWCOMBE 1 



Carnegie Institution, Cold Spring Harbor, N. Y. 



Received April 24, 1948 

 INTRODUCTION 



THE quantitative study of mutations occurring at low rates requires an 

 organism that can be grown conveniently in large numbers, and mutations 

 that can be readily detected. Furthermore, where information is desired con- 

 cerning the effect of a gene change shortly after its occurrence, it is necessary 

 to be able to examine the phenotype of the organism immediately following the 

 change and at intervals thereafter. 



Bacteria are superior to higher organisms for these purposes, since (1) large 

 populations can be handled, (2) there are numerous mutants that can be readily 

 detected and counted, and (3) individual organisms result from each cell 

 division, enabling the phenotype to be determined at any time after a gene 

 change. It was the purpose of this investigation to discover the rate of spon- 

 taneous mutation of the bacterium Escherichia coli, strain B/r, from sensi- 

 tivity to resistance to the phage 77, and also, by indirect means, to determine 

 the interval between time of occurrence of the mutation and phenotypic ex- 

 pression. 



The reasons for investigating spontaneous mutation rate and time of pheno- 

 typic expression are as follows: 



Two previously developed methods of estimating mutation rate in bacteria 

 have yielded discrepant results (Luria and Delbruck 1943). This discrepancy 

 has been ascribed to an error in the assumptions on which one of the methods 

 is based; but, which assumption and which method is in error is not known. 



One of the methods rests on the assumption that a gene mutation expresses 

 itself immediately in the individual cell in which it occurs; and one of the 

 possible interpretations of the discrepancy is that this is not the case, but that 

 on the contrary one or more generations of growth are required before the 

 mutation is expressed. 



Delayed phenotypic expression, or "cytoplasmic lag" as it has been termed, 

 has been observed in Paramecium (see Sonneborn 1947); and if something of 

 this nature occurs also in bacteria it is important from the standpoint of under- 

 standing gene action. 



* The cost of the accompanying tables has been paid by the Galton and Mendel Memorial 

 Fund. 



1 Present address: Biological and Medical Research Branch, National Research Council, 

 Atomic Energy Project, Chalk River, Ontario, Canada. 



[Reprinted by permission from Genetics 33:447-476, September, 1948] 



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