A Structure for Deoxyribo Nucleic Acid
J. D. Watson and F. H. C. Crick (1)
April 25, 1953 (2), Nature (3), 171, 737-738
We wish to suggest a structure for the salt of deoxyribo nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.
A structure for nucleic acid has already been propod by Pauling (4) and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bas on the outside. In our opinion, this structure is unsatisfactory for two reasons:
(1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other.
(2) Some of the van der Waals distances appear to be too small.
Another three-chain structure has also been suggested by Frar (in the press). In his model the phosphates are on the outside and the bas on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.
We wish to put forward a radically different structure for the salt of deoxyribo nucleic acid (5). This structure has two helical chains each coiled round the same axis (e diagram). We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining beta-D-deoxyribofurano residues with 3',5' linkages. The two chains (but not their bas) are related by a dyad perpendicular to the fibre axis. Both chains follow right-handed helices, but owing to the dyad the quences of the atoms in the two chains run in opposite directions (6) . Each chain looly rembles Furberg's2 model No. 1 (7); that is, the bas are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it i
s clo to Furberg's "standard configuration," the sugar being roughly perpendicular to the attached ba. There is a residue on each every 3.4 A. in the z-direction. We have assumed an angle of 36° between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10 A. As the phosphates are on the outside, cations have easy access to them.
Figure 1
This figure is purely diagrammatic (8). The two ribbons symbolize the two phophate-sugar chains, and the horizonal rods the pairs of bas holding the chains together. The vertical line marks the fibre axis.
The structure is an open one, and its water content is rather high. At lower water contents we would expect the bas to tilt so that the structure could become more compact.
The novel feature of the structure is the manner in which the two chains are held together
by the purine and pyrimidine bas. The planes of the bas are perpendicular to the fibre axis. They are joined together in pairs, a single ba from one chain being hydroden-bonded to a single ba from the other chain, so that the two lie side by side with identical z-coordinates. One of the pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6.
If it is assumed that the bas only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bas can bond together. The pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine) (9).
In other words, if an adenine forms one member of a pair, on either chain, then on the assumptions the other member must be thymine; similarly for guanine and cytosine. The quence of bas on a single chain does not appear to be restricted in any way. However, if only specific pairs of bas can be formed, it follows that if the quence of b
as on one chain is given, then the quence on the other chain is automatically determined.
It has been found experimentally3,4 that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very clo to unity for deoxyribo nucleic acid.
It is probably impossible to build this structure with a ribo sugar in place of the deoxyribo, as the extra oxygen atom would make too clo a van der Waals contact.
The previously published X-ray data5,6 on deoxyribo nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of the are given in the following communications (10). We were not aware of the details of the results prented there when we devid our structure (11), which rests mainly though not entirely on published experimental data and stereochemical arguments.
It has not escaped our notice (12) that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
