"Molecular Structure of Nucleic Acids: a Structure for Deoxyribose Nucleic Acid - J.d. Watson, F.h.c. Crick."

ADVERTISEMENT
No. 4356
April 25, 1953
NATURE
737
This figure is purely
diagrammatic. The two
ribbons symbolize the
two phosphate-sugar
chains, and the hori-
zontal rods the pairs of
bases holding the chains
together. The vertical
line marks the fibre axis
equipment, and to Dr. G. E. R. Deacon and the
captain and officers of R.R.S.
Discovery II
for their
part in making the observations.
1
Young, F. B., Gerrard, H;, and Jevons, W., Phil. Mag., 40, 149
(1920).
• Longuet-Higgins, M. S., Mon. Not. Roy. Astra. Soc., Geophys. Supp.,
6, 285 (1949).
• Von Arx, W. S., Woods Hole Papers in Phys. Oceanog. Meteor., 11
(3)
(1950).
'Ekman, Y. W.. Arkiv. Mat. Astron. Fysik. (Stockholm), 2 (11) (1905).
MOLECULAR STRUCTURE OF
NUCLEIC ACIDS
A Structure for Deoxyribose Nucleic Acid
W
E 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'. They kindly made
their manuscript available to us in advance of
publication.
Their model consists of three inter-
twined chains, with the phosphates near the fibre
axis, and the bases on the outside. In our opinion,
this structure is unsatisfactory for two reasons:
(I)
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 del' Waals
distances appear to be too small.
Another three-chain structure has also been sug-
gested 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 di-
ester groups joining
~-D-deoxy­
ribofuranose 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
Fur"
berg's' model No.1;
that is,
t
he 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 perpendi-
cular to the attached base. There
is a residue on each chain every 3·4 A. in the z-diree-
tion.
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. They are joined
together in pairs, a single base from one chain being
hydrogen-bonded to 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 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 bases only occur in the
structure in the most plausible tautomeric forms
(that is, with the keto rather than the enol con-
figurations) 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
~ther
words, if an adenine forms one member of
a pair, on either chain, then on these assumptions
the other member must be thymine; similarly for
guanine and cytosine.
The sequence of bases on a
single cl1ain 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
ono chain is given, then the sequence on the other
chain is automatically determined.
It has been found experimentally3,. that the ratio
of the amounts of adenine to thymine, and the ratio
of guanine to cytosine, are always very close to unity
for deoxyribose 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
del' Waals contact.
The previously published X-ray data
5 • 6
on deoxy-
ribose 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 stereo-
chemical arguments.
It has not
es~aped
our notice that the specific
pairing we have postulated irrimediately suggests a
possible copying mechanism for the genetic material.
Full details of the structure, including the con-
ditions 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 inter-
atomic 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. H. E. Franklin and their co-workers at
©
1953
Nature Publishing Group
No. 4356
April 25, 1953
NATURE
737
This figure is purely
diagrammatic. The two
ribbons symbolize the
two phosphate-sugar
chains, and the hori-
zontal rods the pairs of
bases holding the chains
together. The vertical
line marks the fibre axis
equipment, and to Dr. G. E. R. Deacon and the
captain and officers of R.R.S.
Discovery II
for their
part in making the observations.
1
Young, F. B., Gerrard, H;, and Jevons, W., Phil. Mag., 40, 149
(1920).
• Longuet-Higgins, M. S., Mon. Not. Roy. Astra. Soc., Geophys. Supp.,
6, 285 (1949).
• Von Arx, W. S., Woods Hole Papers in Phys. Oceanog. Meteor., 11
(3)
(1950).
'Ekman, Y. W.. Arkiv. Mat. Astron. Fysik. (Stockholm), 2 (11) (1905).
MOLECULAR STRUCTURE OF
NUCLEIC ACIDS
A Structure for Deoxyribose Nucleic Acid
W
E 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'. They kindly made
their manuscript available to us in advance of
publication.
Their model consists of three inter-
twined chains, with the phosphates near the fibre
axis, and the bases on the outside. In our opinion,
this structure is unsatisfactory for two reasons:
(I)
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 del' Waals
distances appear to be too small.
Another three-chain structure has also been sug-
gested 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 di-
ester groups joining
~-D-deoxy­
ribofuranose 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
Fur"
berg's' model No.1;
that is,
t
he 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 perpendi-
cular to the attached base. There
is a residue on each chain every 3·4 A. in the z-diree-
tion.
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. They are joined
together in pairs, a single base from one chain being
hydrogen-bonded to 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 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 bases only occur in the
structure in the most plausible tautomeric forms
(that is, with the keto rather than the enol con-
figurations) 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
~ther
words, if an adenine forms one member of
a pair, on either chain, then on these assumptions
the other member must be thymine; similarly for
guanine and cytosine.
The sequence of bases on a
single cl1ain 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
ono chain is given, then the sequence on the other
chain is automatically determined.
It has been found experimentally3,. that the ratio
of the amounts of adenine to thymine, and the ratio
of guanine to cytosine, are always very close to unity
for deoxyribose 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
del' Waals contact.
The previously published X-ray data
5 • 6
on deoxy-
ribose 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 stereo-
chemical arguments.
It has not
es~aped
our notice that the specific
pairing we have postulated irrimediately suggests a
possible copying mechanism for the genetic material.
Full details of the structure, including the con-
ditions 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 inter-
atomic 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. H. E. Franklin and their co-workers at
©
1953
Nature Publishing Group
738
NATURE
April 25, 1953
VOL. 171
King's College, London. One of us
(J.
D. W.) has been
aided by a fellowship from the National FOlUldation
for Infantile Paralysis.
J. D.
'WATSON
F. H.
C. CRICK
Medical Research Council Unit for the
Study of the Molecular Structure of
Biological Systems,
Cavendish Laboratory, Cambridge.
April 2.
1
Pauling, I,., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S.
Nat. Acad. Sci., 39,
84
(1953).
2
Jo'urberg, S., Acta Chem. Scand., 6, 634 (1952) .
• Chargaff, E., for references see Zamenhof, S., Brawerman, G., and
Chargaff, E., Biochim. et Biophys. Acta, 9, 402 (1952) .
• Wyatt. G. R.,
J.
Gen. Phys'iol., 36, 201 (1952).
, Astbury, W.
'1.'.,
Syrnp. Soc. Exp. BioI. I, Nucleic Acid, 66 (Camb.
Dniv. Press, 1947).
• Wilkins, M. H.
:1<' . ,
and Randall, J. '1.'., Biochim. et Biophys. Acta.
10. 192 (1953).
Molecular Structl,lre of Deoxypentose
Nucleic Acids
'WHILE
the biological properties of deoxypentose
nucleic acid suggest a molecular structure con-
taining great complexity, X-ray diffraction studies
described here (cf. Astburyl) show the basic molecular
configuration has great simplicity.
The purpose of
this communication is to describe, in a preliminary
way, some of the experimental evidence for the poly-
nucleotide chain configuration being helical, and
existing in this form when in the natural state. A
fuller account of the work will be published shortly.
The structure of deoxypentose nucleic acid is the
same in all species (although the nitrogen base ratios
alter considerably) in nucleoprotein, extracted or in
cells, and in purified nucleate. The same linear group
of polynucleotide chains may pack together parallel
in different ways to give crystalline l -
3 ,
semi-crystalline
or paracrystalline material.
In all cases the X-ray
diffraction photograph consists of two regions, one
determined largely by the regular spacing of nucleo-
tides along the chain, and the other by the longer
spacings of the chain configuration. The sequence of
different nitrogen bases along the chain is not made
visible.
Oriented paracrystalline deoxypentose nucleic acid
('structure B' in the following communication by
Franklin and Gosling) gives a fibre diagram as shown
in Fig. I (cf. ref. 4).
Astbury suggested that the
strong 3
·4-A.
reflexion corresponded to the inter-
nucleotide repeat along the fibre axis. The "-' 34 A.
layer lines, however, are not due to a repeat of a
polynucleotide composition, but to the chain con-
figuration repeat, which causes strong diffraction as
the nucleotide chains have higher density than the
interstitial water.
The absence of reflexions on or
near the meridian immediately suggests a helical
structure with axis parallel to fibre length.
Diffraction
by
Helices
It may be shown" (also Stokes, unpublished) that
the intensity distribution in the diffraction pattern
of a series of points equally spaced along a helix is
given by the squares of Bessel functions. A uniform
continuous helix gives a series of layer lines of spacing
corresponding to the helix pitch, the intensity dis-
tribution along the nth layer line being proportional
to the square of J
n,
the nth order Bessel function.
A straight line may be drawn approximately through
Fig. I. Fibre diagram of deoxypentosc nucleic acid from B. coli.
Fibre axis vertical
the innermost maxima of each Bessel flUlction and
the origin. The angle this line makes with the equator
is roughly equal to the angle between an element of
the helix and the helix axis. If a unit repeats n times
along the helix there will be a meridional reflexion
(J
0 2 )
on the nth layer line. The helical configuration
produces side-bands on this fundamental frequency,
the effect
5
being to reproduce the intensity distribution
about the origin around the new origin, on the nth
layer line, corrosponding to C in Fig. 2.
We will now briefly analyse in physical terms some
of the effects of the shape and size of the repeat unit
or nucleotide on the diffraction pattern. First, if the
nucleotide consists of a unit having circular symmetry
about an axis parallel to the helix axis, the whole
diffraction pattern is modified by the form factor of
the nucleotide. Second, if the nucleotide consists of
a series of points on a radius at right-angles to the
helix axis, the phases of radiation scattered by the
helices of different diameter passing through each
point are the same. Summation of the corresponding
Bessel functions gives reinforcement for the inner-
. /
Co
...........
~
~
,
,
.
,
/
.
,
,
.
,
A
A
,
A
A
,
,
~
:-
A
A
:-
---:
~
A A
-+
B
.:..-
---.:.
~ ~
B
B
~
/
"-
B
~
0
Fig. 2. Diffraction pattern of system of helices corresponding to
structure of deoxypentose nucleic acid.
The squares of Bessel
functions arc plotted about 0 on the equator and on the first,
second, third and fifth layer lines for half of the nucleotide mass
at 20 A. diameter and remainder distributed along a radius, the
mass at a l(iven radius being proportional to the radiu.. About
C
on the tenth layer line similar functions are plotted for an outer
diameter of 12 A.
©
1953
Nature Publishing Group
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