December 16, 1962

Dear Alex:

I've just finished reading your review on somatic phases in plants, enjoyed
it very much, and want to thank you ‘or sending me the reorint. JI had browsed
into some of that literature when I was thinking about phase variation in | Sal-
monella, and it is welcome to have it tied together as you have.

There is one point about the problem that still elddes me. Like ;ourself, I
incline strongly to a paramutational (or epinucleic) interpretation of develon-
ment, and would like to focus on the aptest exnerimental material. (Frustration

I about not reacting the chemistry of 3k genetic transfer in Salmonella is what

, pushed us into Bacillus subtilis work-- where, so far, we have seen no phenomena
of chase differentiation). Is there any particular evidence that the somatic phase
in plants is even a cellular svecificity (apart from its intracellular seat)?
I could, for example, readily imagine that the inter-cellular pattern of the
meristem could be self-pvropagating, and determine the nhase. To answer this,
one would have to show that an isolated cell has a definite phase, and I could
fini no inlication about this in your review. Is there exnerimental material,
showing phase variation, where one can propagate from an isolated cell of a
meristem of either phase? (Transvlant will do as well as exvlant provagation). |
I do believe that a definite answer to this issue is an essential next steno. If
it is not experimentally feasible, then I would have to question whether we are
ready to penetrate much further into the problem with volant material.

On the chemical side, we have to be thinking of more definite, esnecially
testable sodels of wnat is happening to, or near, the DNA. Since the organization
of chromosomes parallels the »ohylorsenetic elabomation of somatic dif‘erentiation,
we clearly io not have to rely entirely on changes in the volynucleotide itself,
and I think one of the most attractive hypotheses is the simplest -- that some
genes are broken, by nuclease action, at exnosed nodes, and thus prevented fro-.
working in the further history a ae The breaks are not necessarily completely
irreversible-- a repair enzyme f -eh8o reform the diester brijges. The weakness
of this ijea is its suppositions about chromosome structure -- visible, effective
chromosome breaks must then be a special category of vnolynucleotide scissions. In
plant material it is particularly provocative that the DNA cytosine is vartly
methylatel, probably variably amone different tissues. It would be very enter-
taining to see whether the distribution of methyleytosine was the same in DIA from
alternative phases. The methylation alamost certainly aceurs after the synthesis
of the nolrmucleotite; however, the control of formation of the methylating enzyme,
among others, might devend on the methylation of the cytosine of the DNA of the
corresponiing gene. Again, the success of such an exneriment depends on &y® access
to a good exnerimental system, not too much con*ounded with the metabolic consequences

fo the phase dif’erence.

With best wishes,
As ever,

 

Joshua Lederbers

Qirbdrg re)