DEPARTMENT OF ORGANISMIC AND EVOLUTIONARY BIOLOGY
HARVARD UNIVERSITY

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DANIEL L. HARTL LABORATORY TEL (617) 496-3917
16 DIVINITY AVENUE November 27, 1995 jap (617) 496-5540
CAMBRIDGE, MASSACHUSETTS 02138 FAX (617) 496-5854

Dr Joshua Lederberg wore
Founder's Hall Mo

Rockefeller University fo

1230 York Avenue, STE 400 be 11595
New York, NY 10021-6341 N

Dear Josh:

Many thanks for your letter. Your recollection that you did not practice selection
for crossing ability makes the "Lederberg-lab" hypothesis quite shaky. Your
reference to the years 1922-1945 when the K-12 strain was being stored and
subcultured reminded me of some recent work on long-term stab cultures of

E. coli. For reasons still not understood, these conditions induce IS element
transposition, in some cases very dramatically. So it seems to me that you are
probably right. A combination of storage and subculturing would favor a
mutation that was derepressed for transfer, and the most likely type of mutation
might very well be an IS insertion.

Thanks again for your help. I'm glad you enjoyed my speculative binge. I found
it rather fun.

Best fegards,

ff
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Daniel L. Hartl
Professor of Biology