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The Francis Crick Papers

Letter from Francis Crick to H. Gobind Khorana pdf (121,243 Bytes) transcript of pdf
Letter from Francis Crick to H. Gobind Khorana
Crick consulted Khorana, the first to synthesize a gene from its component nucleotides, as a fellow expert on the genetic code and its action in protein synthesis.
Number of Image Pages:
2 (121,243 Bytes)
1969-03-06 (March 6, 1969)
Crick, Francis
Khorana, H. Gobind
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
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Reproduced with permission of the Wellcome Library for the History and Understanding of Medicine.
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Medical Subject Headings (MeSH):
Genetic Code
Exhibit Category:
Embryology and the Organization of DNA in Higher Organisms, 1966-1976
Metadata Record Letter from Francis Crick to H. Gobind Khorana (April 16, 1969) pdf (53,714 Bytes) transcript of pdf
Metadata Record Letter from H. Gobind Khorana to Francis Crick (April 12, 1969) pdf (270,220 Bytes) transcript of pdf
Box Number: 9
Folder Number: PP/CRI/D/1/1/11
Unique Identifier:
Document Type:
Letters (correspondence)
Physical Condition:
Series: Correspondence
SubSeries: Alphabetical Correspondence
SubSubSeries: Correspondence 1
Folder: Correspondence K
6 March 1969
Dear Gobind
There are two points about which I would like to write to you. The first concerns the sequence of alanine tRNA from yeast. Please, please don't tell Bob Holley, but I have a horrible suspicion that there may be a mistake in his sequence. The area about which I am doubtful is the so-called dihydro U loop. In every structure to date there is a certain regularity starting from the 5- and of the molecule. It starts off with the 7 base pairs. Then there is an unpaired U, or U derivative. Next there is a purine. Then follow 4 bases of which at least 3 are usually base-paired. In every other sequence, immediately after this, there comes A followed by a G. In Bob's sequence, however, GU appears before the AG. This is now so exceptional that I think we must consider the possibility that there is a mistake.
At first sight it might appear that the correct sequence should have the GU omitted. I think it is more likely, however, that the two incorrect additional bases are, in fact, GC. In other words, that the sequence starting at base number 10 should read GCGUAG . . . You will immediately see that this is quite an easy mistake to make. Digestion, either by ribonuclease or by T1, would chop up this sequence into dinucleotides. It would therefore have to be determined by a partial digest. You will note that the sequence GCGCG also occurs in another place, that is starting at position 24. Moreover, one should also allow for the fact that Holley's sample might have been a mixture of two closely related sequences, as was the case of Zachau's serine, and in several other examples. I have not checked back to Bob's original paper; in the ordinary way, I would not bother with this sort of thing unduly, but since you are engaged in making the gene for this transfer RNA I do think it would be a wise precaution if you checked that part of the sequence to your own satisfaction.
My second point concerns the matter I raised with you in my letter of the 9th January. Malcolm Gefter is still very keen to obtain some of your repeating UAG polymer. I quite forgot to ask you about this when you were at La Jolla, mainly because we had so many other things to talk about. Do send us a little if you can spare it.
My lecture on transfer RNA at Stanford went rather better than I expected, and the whole visit was very worthwhile. It is nice to visit a campus where there are so many people doing such good work.
F.H.C. Crick
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