August 14, 1956

Dr. P. D. Skaar
Biological Laboratories
Cold Spring Harbor, L.I., N.Y.

Dear Dave:

We've been away and back, and in and out, and had other things préssing, so
I haven't gotten to your ma. on sequantial gene transfer in time to be ang
critical use to you, but here's how anyhow. What are your publicationg plans

on this?
and preponderant

Jacob has been making such a plausible/oase for the sequence hypothesis
that I wonder xX€xx if there is much point in my maintaingng any cautionary
reserve on it any longer. It certainly doesn't seam like a bad idea, but I
only wish 1t were possible to make a unified theory that would include the
diploid data as well. It 1s not too hard to imagine that the characteristic
point of breakage 1a (at least often) postzygotic in effect, and that this is
superimposed on breakages from interrupted conjugations. The uniformity of the
diploids would then depend a) on the regularity of breakage proximal to Mal, ani
b) marker-choice bias for nondisfunctions still haterozygous for the markers
proximal to the break. Or, instead of b), nondisjunction may not happen unless
most of the proximal region had participated in fertilization. I still do think
that an examination of nondiajunctional types might give the most direct evidence
for a varlabliity of fertilization types.

As to the 2s., I suppose you really will have to get most of your critician
from Jacob. You have an accumulation of conjugants over 40+ minutes; he says
the mating is completed almost instantly.

It might help to understand the figure af you wrote the following equivalents:
(p= pair; z= aygotes):

Malv = pto.z Lascv=p+p.g+g Lasy.T6 = 2 + pew
pe 2 Lac vy as I used it implied a continuous variegation. I have used, and
would prefer Lacg for Lac-sectored. At the least, the distinction in behavior
upon replating should be emphasized.

Pe3 last paragraph: what is expected, yes or no?

pel line 5: Do you attribute observations on exsonjugants to Hayes??

pe6 Ref. 10 You really ought to quote Nelson ani Lederberg 1954 on this.
There we did consider that elimination might be both pre~ and postzygotic, but

thought (possibly wrongly) that this was superfluous. It still doesn't have
to be wardable points of breakage; what you observe, is variable incidence of
"ineépporation"—— to give the most concrete model, stress on a chromosome
region could influence pairing and crossing-over. Without pairing, the
distal markers can't be recovered. That gene transfer may be normally partial
is an economical working hypothesis, if you mean it ought to be sometimes
partial. The generality of... complete transfer is open 4o question, but it
looks to me as if there is evidence for both//.

Figure 2: Why are discontinuities a function of time unless your plating
procedure is disrupting pairs?

oe Me Ee ee tr MR OE ee ee,

to
We are very sorry not/have seen you at all this sumer. The meeting sehedules
thia year were almost criminal; I can't understand this craze to have these topics
(and the audiences) beaten over the head so often. Baltfmore and Ann Arbor
were too much already; we ran away to Woods Hole for a couple of weeks.

Last year was rather brutally taken tp in writing papers & moving troubles etc;

I'm looking forward to seeing what a lab is like again. We are rather more com
fortablg set up in the remodelled lab now. I'm hoping to spend some time on proto-
plasts for transductional experiments, and to finish up studies on a series of

new xuxk Hfr mitants we isolated last year. Alan Richter and I haven't forgotten
about F and motility & will try to get that out of the way (for our mtual relief })
as soon as possihle, Unfortunately, we have been on the verge of a clean proof

af a selective effect, but haven't quite made it yet. (Did you see Hirota ani Kikkawa
in Nature; I'm not quite sure whether the imkmk believe it; Alan did one run, quite
unsuccessfully, )

What are your plans next year?

Yours sincerely
& best to Linda

Joshua Lederberg

P.S. ?? reprints of binary mtability.....

PPS. I warned you it might happen: Marcus Rhoades had the story rather garbled,

thinking it was a specific interac$ion between two loci. (This may show in ihe
Baltimore proceedings, )