DEPARTMENT OF ORGANISMIC AND EVOLUTIONARY BIOLOGY HARVARD UNIVERSITY 8: :CO aTASIE DANIEL L. HARTL LABORATORY TEL (617) 496-3917 16 DIVINITY AVENUE November 14, 1995 | a8 (617) 496-5540 CAMBRIDGE, MASSACHUSETTS 02138 FAX (617) 496-5854 Dr Joshua Lederberg Founder's Hall Rockefeller University 1230 York Avenue, STE 400 New York, NY 10021-6341 Dear Josh: We have recently finished a study of the distribution of plasmids related to F in natural isolates of E. coli that has caused me to speculate on the origin of the F factor in laboratory strains. The thought is summarized in the following passage from the Discussion of the paper I am working on. I am hoping that you will have a look at it and tell me whether you think the scenario is plausible and, if not, why not. "Our data also bear on the history of the F factor in laboratory strains. It has often been remarked that LEDERBERG was extremely lucky to use a Strain in which the F factor was derepressed owing to an insertion of IS3 in the finO gene. However, the frequency of F-related plasmids in the ECOR strains shows that there is a reasonable chance that any randomly selected strain might have such a plasmid: 7 percent, of the ECOR strains have an F plasmid and 11 percent have an R plasmid. What is remarkable in the laboratory F factor is the insertion mutation in finO. In our PCR amplifications of the 28 finO genes in plasmids in the ECOR collection, not one produced a product other than the expected size. When did the insertion in the laboratory F factor take place? Probably not in nature. We suspect that it happened in LEDERBERG'S own laboratory as various subcultures of K-12 were isolated and examined for their ability to undergo recombination. Any subculture with an insertion in finO would be a good at recombination, and such a strain would certainly have been used in further experiments. Hence, a chance insertion of IS3 interrupting finO may well have been the result of unconscious selection -- a case of chance favoring the prepared mind." Many thanks for your consideration. Best DaniƩl L. Hartl v Professor of Biology