UNIVERSITY OF CAMBRIDGE : DEPARTMENT OF GENETICS

HEAD OF DEPARTMENT

Balfour Professor of Genetics

K. J. R. E1)WAKr)S. M.A.. I'ti I).

J. M. THODAY. Sc.D., F.K S.

Our Ref:GAD/JH

DOWNING STREET
CAMBRIDGE CB2 3EH
    0223 69551

8th November, 1982.

Dr. Maxine Singer,
Department of Health, Education & Welfare,
National Institute of Health,
Building 37, Rm 4E28,
Bethesda,
Maryland 20205,
U.S.A.

Dear Maxine,

  No doubt you've seen Lewin's report on molecular drive (Science 218 552-3).
At least he's got right that molecular drive is a system of (a) fixation and (b)
with a particularly synchronous pattern of fixation.
remarks by cotmnentators which puzzle me, at least those of Jeffreys. We've
replied to these and I'm enclosing a copy of our letter to Science.
to Alu I guess he's picked up on your remarks at Heidelberg i.e.  the absence of
a difference in within- and between-species divergence in the primate Alu.
are these data published? I'm very interested to look at them. I'm not sure if
they were your own data.   If they are, could you send me a copy of any paper you
have on this, if it's not yet published?

-

However, there are a few

With respect


     Idhere

-1

-

You'll see from our enclosed letter, that we regard the observed levels of

divergence at any one time to reflect the differences in rates between homogenisation
and mutation.
itself.  What really interests us is if there has ever been a systematic search
for a species diagnostic variant, indicative of separate homogenisation in each
primate species? TJnless this is done, in the way for example Steve Brown did in
the MIF-family, then it's always difficult to interprete divergence levels.
is especially difficult if the levels are taken from a handful of clones in each
species.  A family like Alu with 500,000 members is bound to have both divergent
isolated members and also a subfamily structure.
clones really represent?
subfamilies (:.e. partial homogenisation of a diagnostic variant); however
surprisingly these subfamilies are present in all species - but to different
extents (data in preparation).
patterns, but nevertheless the differences in abundance of the different subfamilies
between species, suggests that MIF is undergoing a process of homogenisation in
each species and that different subfamilies are either on the way in or on the way
out.
lead to an equilibrium situation.

There are many factors influencing this, not least the family

This

The question is what do  the

We know that MIF in 5 species of rodents has  several

There are several complex interpretations  of these

Or alternatively the constraints on large family total homogenisation might

OF

.L

All these typedata come Srom whole-family analysis.

They would not have been

revealed by sequencing a few clones - although we have this as well in MIF which
tell us other things as well - but that's another story.  So even though there has
been a clear homogenisation between rodent and human Alu family counterparts (see
enclosed) - revealed mainly by whole family studies - the question is, is it really

continued.

-2-

as slow as to be only detectable when one goes as far back in the species phylogeny
as rodent versus man. Could it be that there are also distinct whole family or
subfamily differences between primate species indicative of a faster rate of

homogenisation. 7

Is there anything in the Alu data that throws any light on this? Or

better, are there any data that definitely rules out some homogenisation since
primate species separation?  Given the debate now initiated in Science, we are
very eager to know.

With very best regards.

Enc .

Yours sincerely,