We wish to suggest a structure for the salt of deoxyribose nucleic acid(D.N.A.). This structure has novel features which are of considerable biologicalinterest.
A structure for nucleic acid has already been proposed by Paulingand Corey (1). They kindly made their manuscript available to us in advanceof publication. Their model consists of three intertwined chains, with thephosphates near the fibre axis, and the bases on the outside. In our opinion,this structure is unsatisfactory for two reasons: (1) We believe that thematerial 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 holdthe structure together, especially as the negatively charged phosphatesnear the axis will repel each other. (2) Some of the van der Waals distancesappear to be too small.
Another three-chain structure has also been suggested by Fraser (in thepress). In his model the phosphates are on the outside and the bases onthe inside, linked together by hydrogen bonds. This structure as describedis 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 ofdeoxyribose nucleic acid. This structure has two helical chains each coiledround the same axis (see diagram). We have made the usual chemical assumptions,namely, that each chain consists of phosphate diester groups joining ß-D-deoxyribofuranoseresidues with 3',5' linkages. The two chains (but not their bases) are relatedby a dyad perpendicular to the fibre axis. Both chains follow right- handedhelices, but owing to the dyad the sequences of the atoms in the two chainsrun in opposite directions. Each chain loosely resembles Furberg's2 modelNo. 1; that is, the bases are on the inside of the helix and the phosphateson the outside. The configuration of the sugar and the atoms near it isclose to Furberg's 'standard configuration', the sugar being roughly perpendicularto the attached base. 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 samechain, so that the structure repeats after 10 residues on each chain, thatis, after 34 A. The distance of a phosphorus atom from the fibre axis is10 A. As the phosphates are on the outside, cations have easy access tothem.
The structure is an open one, and its water content is rather high. Atlower water contents we would expect the bases to tilt so that the structurecould become more compact.
The novel feature of the structure is the manner in which the two chainsare held together by the purine and pyrimidine bases. The planes of thebases are perpendicular to the fibre axis. The are joined together in pairs,a single base from the other chain, so that the two lie side by side withidentical z-co-ordinates. One of the pair must be a purine and the othera pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1 ; purine position 6 to pyrimidineposition 6.
If it is assumed that the bases only occur in the structure in the mostplausible tautomeric forms (that is, with the keto rather than the enolconfigurations) it is found that only specific pairs of bases can bond together.These pairs are : adenine (purine) with thymine (pyrimidine), and guanine(purine) with cytosine (pyrimidine).
In other words, if an adenine forms one member of a pair, on either chain,then on these assumptions the other member must be thymine ; similarly forguanine and cytosine. The sequence of bases on a single chain does not appearto be restricted in any way. However, if only specific pairs of bases canbe formed, it follows that if the sequence of bases on one chain is given,then the sequence on the other chain is automatically determined.
It has been found experimentally (3,4) that the ratio of the amountsof adenine to thymine, and the ration of guanine to cytosine, are alwaysbery close to unity for deoxyribose nucleic acid.
It is probably impossible to build this structure with a ribose sugarin place of the deoxyribose, as the extra oxygen atom would make too closea van der Waals contact. The previously published X-ray data (5,6) on deoxyribosenucleic acid are insufficient for a rigorous test of our structure. So faras we can tell, it is roughly compatible with the experimental data, butit must be regarded as unproved until it has been checked against more exactresults. Some of these are given in the following communications. We werenot aware of the details of the results presented there when we devisedour structure, which rests mainly though not entirely on published experimentaldata and stereochemical arguments.
It has not escaped our notice that the specific pairing we have postulatedimmediately suggests a possible copying mechanism for the genetic material.
Full details of the structure, including the conditions assumed in buildingit, together with a set of co-ordinates for the atoms, will be publishedelsewhere.
We are much indebted to Dr. Jerry Donohue for constant advice and criticism,especially on interatomic distances. We have also been stimulated by a knowledgeof the general nature of the unpublished experimental results and ideasof Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King'sCollege, London. One of us (J. D. W.) has been aided by a fellowship fromthe National Foundation for Infantile Paralysis.
Medical Research Council Unit for the Study of Molecular Structure ofBiological Systems, Cavendish Laboratory, Cambridge. April 2.
1. Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S.Nat. Acad. Sci., 39, 84 (1953).
2. Furberg, S., Acta Chem. Scand., 6, 634 (1952).
3. Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff,E., Biochim. et Biophys. Acta, 9, 402 (1952).
4. Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).
5. Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ.Press, 1947).
6. Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta, 10,192 (1953).