April 13, 1953

Dr. K. Mather

Department of Genetics
The University, Edgbaston
Birminghan 15, England

Dear Mather:

I am moved to write now partly in recollection of our very pleasant
and (to me) fruitful correspondence of six years ago, but primarily from
the provocation of Rees & Binks! recent paper in Phoc. Roy. Soc. on the
mechanism of nuclear adjustment in heterokaryons. It seems to me they
have neglected the mat likely possibility, namely that hyphae with differing
ratios of nuclei are produced by random fluctuations, and that those hyphae
th the mst adaptive ratios proliferate the fastest. I am writing to you,
as their professor, because I am more confident (from past experience) of
being able to communicate with you.

Since the linkage analysis, for your help on which I whbhin indebted,
E. cold genetics seems to have moved into greater and greater complexity.
Despite some current speculations, however, there is fairly explicit evidence
that any eliminations of gametic components are post-sygotic. For example ,
there have been many diploid heterozygotes which, though deficient in the
Mal-S segment, have received the Mal allele from one parent, the 3 from the
other (e.g.the Mal+ 8° of table 6A in my 1951 CSH paper). There is still no
factual evidence (despite contrary speculation, again) that any agents other
than intact cells function in E. coli recombination, and we have some hopes
(and even some suggestive appearances) from cytological studies in progress.
I do not see how selective recovery of prototrophs can play an appreciable
role in distorting segregation ratios. Despite minor inconsistencies, whic}
are, by the way less appreciable than the variance for replications of-agi-
a given cross iwhich Balley seems to have overlooked], the ratios from reverse
crosses are in too good agreement. Some minor discrepancies may result from
competitive suppression, but we have never seen it in reconstruction experiments.
The conditions under which most workers have studied reverse mutation in
bacteria and Neuroppora, and their explicit experiments not always mentioned
in print, make it unlikely that their results are seriously questionable.
However, there was a time when J was emphasizing (perhaps overly) the same
point myself, ¢.g- Heredity,2:162 ff. '48.

With best regards from Mrs. Lederberg,
Sincerely,

Joshua Lederberg
[Associate Professor of Genetics} ~~~