Genetic Recombination in DNA-Induced Transformation of Pneumococcus. I. the Problem of Relative Efficiency of Transforming Factors.

F OLLOWING absorption of DNA by competent cells, genetic transformation ensues with a probability that is characteristic for each particular genetic marker (HOTCHKISS and MURMUR 1954; LERMAN and TOLMACH 1957). Thus, specific incorporation, defined as the amount of DNA which must be incorporated in order to obtain one transformant, varies according to the genetic marker employed. With the development of more elaborate genetic marker systems, notably, systems of linked genes, various causes were postulated as operating in determining the probability that, given DNA incorporation, a certain type of transformant would appear. Thus, arguing from the fact that pairs of linked genes appear together in transformants less often than the same genes ‘appear singly (HOTCHKISS and EVANS 1958), it has been suggested that mutant markers which have different probabilities of integration into a transformed cell have different linear dimensions (LACKS and HOTCHKISS 1960; EPHRUSSI-TAYLOR 1961) . In an interesting series of experiments, SCHAEFFER ( 1958) showed that where transformations are performed between different species of Hemophilus, relatedness, which is presumably an expression of homology of base-pair sequence in DNA, is crucial in determining the probability of integration of a genetic marker into a transformant. Further, in intraspecific transformation in pneumococcus, GREEN (1959) found that certain combinations of donor and recipient led to low transformation frequencies for a particular streptomycin resistance gene. The depressed probability of integration was further shown to be due to the presence of a “depressor” region closely associated with the marker gene, but separable from it by recombination (GREEN 1959; ROTHHEIM 1962). Both of these lines of work indicate the importance of structural homology in determining the probability of integration. Still another cause of low probability of genetic integration has been proposed, though never demonstrated experimentally. Were a particular genetic marker to be located always near the end of a DNA molecule, one might expect it to be