A structure for Deoxyribose Nucleic Acid
2 April 1953
MOLECULAR STRUCTURE OF NUCLEIC ACIDS
A Structure for Deoxyribose Nucleic Acid
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 biological interest.
A structure for nucleic
acid has already been proposed by Pauling
and Corey (1). 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 bases 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 oth
er. (2) Some of the van der Waals distances appear to be too small.
Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates
are on the outside and the bases 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 deoxyribose nucleic acid. This
structure has two helical chains each coiled round the same axis (see diagram). We have made the usual chemical
assumptions, namely, that each chain consists of phosphate diester groups joining ß-D-deoxyribofuranose
residues with 3',5' linkages. The two chains (but not their bases)
are related by a dyad perpendicular to the fibre axis. Both chains follow right- handed helices, but owing to the
dyad the sequences of the atoms in the two chains run in opposite directions. Each chain loosely resembles
Furberg's2 model No. 1; that is, the bases are on the inside of the helix and the phosphates on the outside. The
configuration of the sugar and the atoms near it is close to Furberg's 'standard configuration', the sugar being
roughly perpendicular to 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
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.
The structure is an
open one, and its water content is rather high. At lower water contents we would expect the bases 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 bases. The planes of the bases 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 with identical z-co-ordinates. One of the
pair must be a purine and the other 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 bases 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 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
otherm ember must be thymine ; similarly for guanine and cytosine. The sequence of bases on a single chain does not
appear to be restricted in any way. However, if only specific pairs of bases can be 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 amounts of adenine to thymine, and the ration of
guanine to cytosine, are always very close to unity for deoxy
ribose nucleic acid.
It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose, as the
extra oxygen atom would make too close a van der Waals contact. The previously published X-ray data (5,6) on
deoxyribose 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 these are given in the following communications. We were not aware of the details of the
results presented there when we devised our structure, which rests mainly though not entirely on published
experimental data and stereochemical arguments.
It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible
copying mechanism for the genetic material.
Full details of the structure, including the conditions assumed in building it, together with a set of
co-ordinates for the atoms, will be published elsewhere.
We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic
distances. We have also been stimulated by a knowledge of the general nature of the unpublished
experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King's
College, London. One of us (J. D. W.) has been aided by a fellowship from the National Foundation for Infantile
Paralysis.
J. D. WATSON F. H. C. CRICK
Medical Research Council Unit for the Study of Molecular Structure of Biological 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).
VOL 171, page737, 1953