INTRODUCTION 



or the production of auto- or trans-inhibitory metabolites. An especially clearcut 

 example of the latter in an economically important organism is reprinted here 

 (12). The intricate interrelationships of the production of and sensitivity 

 to species-specific antibiotics ("colicins") have been thoroughly analyzed for 

 E. coli by Fredericq (59). One of the most exhaustive analyses of selection 

 dynamics in bacteria will serve best to illustrate the complexity of populational 

 interactions in which several distinct effects may be superimposed (115). A 

 number of populational interactions have been described with a less complete 

 analysis (138, 136, 85). 



Population complexities may also arise when more than one mutation 

 occurs, so that the population consists of several categories of genotypes. One 

 example has been cited already in the stepwise development of resistance by 

 the cumulative effect of serial mutations. A second has been described so 

 recently that its implications are still under discussion. In independent experi- 

 mental work, three groups of investigators noticed a perplexing sequence of 

 cycles in bacterial populations under conditions of continuous or reiterated 

 culture (25, 106, 124). "Marker" mutant cells increased in proportion as 

 mutations accumulated, but instead of increasing indefinitely, their ratio was 

 subject to sporadic downward shifts. The same interpretation was independently 

 formulated for each case: an adaptive mutation increasing the fit of the 

 bacteria to their rather artificial in vitro environment. Owing to the overwhelm- 

 ing preponderance of the cells not carrying the marker, the adaptive mutation 

 will usually occur in an unmarked cell, the descendants of which will then 

 displace the rest of the population, markers and all. After the changeover, 

 marker mutations accumulate .again until a possible second changeover takes 

 place to complete another cycle. It is not predicted that this process could 

 alter the ultimate equilibrium of cell types under mutation "pressure," but 

 that it would alter the short-term course of cultures in which marker mutation 

 pressures outweigh selection effects is apparent. Such adaptive mutations un- 

 doubtedly serve as models for evolutionary specialization ; as the streptomycin- 

 dependent mutation cited earlier shows most strikingly, genetic adaptations 

 are often quite specific for the immediate environment. This type of specializa- 

 tion undoubtedly accounts for the often noted loss of virulence encountered 

 frequently among pathogenic bacteria maintained on artificial culture media. 



Inter clonal variation: Sexual recombination. — The preceding discussion 

 of bacterial populations has supposed that each bacterial cell is genetically 

 isolated from its partners, i.e., that reproduction is exclusively vegetative or 

 clonal. A large body of evidence is now at hand, however, which shows that 

 this picture is incomplete, and that some account must be taken of interclonal 

 processes. One such process was discovered in 1946 by Tatum and Lederberg 

 (45, 84, 128) and described as genetic recombination, for the experiments are 

 based on the selective isolation of genetic factor combinations from mixtures 

 of different kinds of mutant cells. The conditions under which these genetic 

 exchanges take place, and the patterns in which they result, led these authors 



