REC’D JUN 22 1964
Woods Hole, Mass., June 18 1964
Dear Dr. Pauling :
I much regretted not to be able to wish you good bye as I left Caltech. I was
unaware of your plans to go to your ranch and therefore missed you. But I was happy
to be able to think and am now happy to say : A bientôt !
After the meetings at Cold spring Harbor we spent a few quiet days here in Woods
Hole with my father-in-law and are about to leave for France. I used these days largely
to put in shape the manuscript on the paleogenetics of hemoglobins (the talk I have
in Bruges) of which I left a copy with you.
In this manuscript and in my presentation I gave our table 1 from “Horizons in
Biochemistry” (the approximate time of derivation of different hemoglobin chains from
there common ancestor) with slightly revised figures. The order of magnitude of time
elapsed between two evolutionarily effective mutations still was 10 Million years.
I then proceeded to examine the rate of evolution of cytochrome c and to compare it
with the rate of evolution of hemoglobin. I found the two rates to differ only slightly.
You may not have at hand the figure that relates to these matters, and I am therefore
including another copy of it.
This type of quantitative treatment of the data was criticized at the Bruges
meetings by several participants, notably by Ingram, who felt that the uncertainties
are still to [sic] great to warrant any quantitative statement in relation to the
common ancestors of polypeptide chains.
I was not very impressed with these criticisms. I am however much impressed now
to discover that my own paper…implicitly contained a strong criticism of the above
treatment of the data. One of the three main sections of the paper is devoted to putting
forward and defending the hypothesis that a high degree of morphological similarity
between organisms is accompanied by a high degree or similarity of most polypeptides.
This is thought to apply not only to contemporary organisms that have changed little
in appearance during a given evolutionary span. The most widespread opinion is just
opposite. It is thought that two morphologically similar organisms, if separated by
many millions of years of evolutionary time, are probably biochemically quite different.
If the proposed hypothesis is correct, it follows that if we compare homologous
polypeptide chains from two contemporary forms whereof one is placed low, the other
one high on the evolutionary scale, say man and a fish, one of the chains will have
undergone a great many changes in amino acid sequence since the time of the common
chain-ancestor, the other chain (that of the fish) relatively few. In comparison with
their common ancestor, a contemporary fish indeed has changed morphologically much
less than man. In such a case, the procedure of halving the number of differences
between the two polypeptide chains, in order to arrive at an approximate figure of
the number of evolutionarily effective substitutions that occurred in each line of
descent, is no more valid.
Consequently it cannot be considered that the graph with the data on cytochrome
c represents “the” rate of evolution of cytochrome c. The graph may still have a certain
interest: but since it compares man with all other forms, the error introduced by
an inequality in the amount of evolutionary change that occurred in each pair of lines
of descent since the time of the common ancestor will be the greater, the more distant
on the evolutionary scale the other organism is from man. In relation to the human
line of descent the apparent rate of evolution of cytochrome will be an underestimate,
and with respect to the other line of descent, an overestimate. Perhaps it is possible
to devise a factor of correction that would take into account the vertical distance
on the evolutionary scale, as known from all available evidence, or any two organisms
that are being compared.
It seems to me that our table in “Horizons of Biochemistry” is not critically
affected by this discussion, for the following reasons : we used the differences between
the horse and human alphachains of hemoglobin as the basis for all other calculations.
It may be that the rate of evolution in both the human race and the equine line of
descent, since their common point of origin, has not been drastically different. –
Moreover we used the figure obtained by the comparison of the sequences of human and
equine hemoglobin to calculate the time of common origin of chains, not as they occur
in very different animals, but as they occur within one and the same animal. Although
the rates of evolution of the different homologous chains found in man alone – the
alpha, beta, gamma, delta plus the recently discovered epsilon chain – may even here
differ significantly, the chances appear good that this difference in rate of evolution
is not too great at least in the case of the two “adult” major component chains, the
alpha chain and the beta chain.
I am writing to ask you whether you would like to give me your opinion in relation
to these matters. I intend to introduce into my manuscript a discussion along the
lines indicated in this letter. But since this discussion is directly related to our
“Szent Györgi – paper”, it occurred to me that, in case you would wish to express
your ideas on the subject, I might remove this whole chapter from my “Bruges – paper”
and reserve it for our “Rutgers – paper”. Either procedure would be fine with me.
Unfortunately my “Bruges”-manuscript is overdue, and I shall have to finish it
within the next few days. My address is the following :
Laboratoire de Physico-Chimie Colloldale, Route de Mende, Montpellier, Hérault.
Jane and I are sending you and Mrs. Pauling our affectionate greetings.
Emile
P.S. At Cold Spring Harbor a number of people referred to matters that are treated
in our article published in the book dedicated to Oparin. People refer to Itano, because
he also has described possible consequences of isosemantic substitutions (not so called
by him) and has sent a preprint of his paper to numerous investigators. Our paper
is ignored, because it has been published in russian [sic] in a russian [sic] book.
You once told me that “Evolutionary and Industrial Biochemistry” might be re-edited
in English. Do you know what the chances of such an event are? If the_y are low, could
our article conceivably be reprinted in English in some american [sic] periodical
?
Handwritten: I’m sorry, I can’t find the figure I meant to include. It must be in
a bunk that we shipped over to France directly.
