\s

a degenerate helix, such as a straight line or a circle.
Notice that a helix accounts rather naturally for the long
repeat distance of the structure, as this would correspond
to one turn of the helix. This restriction - that the
phosphate-sugar groups are Spacially uniform - is a great
help in model building as it reduces very considerably the
number of possibilities that have to be explored. Indeed at

first we were unable to build any satisfactory model consistent

with our assumptthons, but eventually we arrived at a structure

which we now belefive to be correct in its broad outlines,
This particular model does not contain just one DNA

chain, but a pair of them, wound round a common axis. These

two chains are linked together by their bases. A base on one

chain is joined by weak physical bonds to a base at the
same level on the obher chain, and all the bases are paired
of in this way right along the structure. This is shown
diagrammatically in Fig. . The general appearance of the
structure is Shown in a Symbolic manner in Fig. » in which
the two ribbons represent the phosphate sugar chains, and the
pairs of bases holding them together are symbolized as |
horizontal rods. It will be found that this figure looks:
exactly the Same upside down , and to preserve this feature
we have built our model so that the actual sequence of atoms

in one ph_osphate-sugar chain is in the opposite direction

to the corresponding Sequence in the other. This ' is shown
symbolically by the two small arrows,

Now it is found that one cannot build this model with |
any bases one pleases; only e@ertain pairs of the four bases
will fit into the structure. In any pair there must always
be one big one (purine) and one little one(pyrimidine).
one tries to put in two purines - two big ones, that is, .
there is not sufficient room for them. Conversely a pair made
of two pyrimidines is too small to bridge the gap between the
two chains. Moreover when one examines in detail how the
hydrogen bonds are formed between the bases it is found that
(making certain plausible assumptions) the pairing is sven

more restricted. The only possible pairs that will fit in |

are

Adenine with Thymine .
and | Guanine with Cytosine.
The way these pairs are formed is shown in Fig. oo

The dotted lines show the weak physical bonds, known as
hydrogen bonds, which nold the two bases of a pair together.
(hydrogen bonds are, for exanple, the main forces holding :
different water molecu'es together, and it is because of them
that water is: a liquid at room temperatures and not a gas)

a ‘These specific pairs” can be built into the structure
either way round. We can have adanine on the first chain 7

paired with ‘thymine on the Second, or vica versa, But it

we do have adenine at some point on one of the chains, it is

i
;
\o

‘chains, therefore, which is at the root of the specific patra

Evidence for the model

essential to have thymine paired with it on the other. It

is impossible to fit in guanine or cytosine or a second

adenine. In the same way guanine must always be paired with

cytosine. |
On the other hand the model places no restriction on the

Sequence of pairs of bases as one proceeds along the structure.

Any ® specific pair can follow any other. specific pair. ‘This |

is because a pair of bases is flat, and as in this model they

are stacked one above another like a pile of coins it does”

not matter which pair goes above which. ; .
This specific pairing of the bases is the direct result

of the aseumpt1on that both phosphate-sugar chains are helical,

This implies that the distance apart of two sugar groups at

_ the same level (one belonging to each chain) is always the

‘same, no matter where one is along the chain. It follows that.

the bases, which are of course linked to the sugars, have
always the same amount of space in which to fit, as can be .
seen from studying Fig. - If it were not for this
restriction the ‘bases cound hy -droren—bond together in many

different ways. It is the rerularity of the phosphate-sugar vg

   

The experimental evidence in support of a model. of this ?
general type is now considerable. Measurements of the density,
and water content of the DNA fibres, taken with. the evidence

showing how the fibres can be extended in length, strongly
suggest that there are two DNA chains in the structural unit.

The X-ray patterns have a large number of places where the

diffraction intensity is zero and these occur exactly where.

one expects them from helical structures of this type. Moreover

the X-ray diffraction data approximates quite closely to

cylindrical symmetry, as it should. Recently Wilkins and hts

co-workers have given a brilliant analysis of the details of

the X-ray pattern of the crystalline form, and have shown that

they are consistent with a structure of this type, though in

this form the bases are not perpendicular to the fibre axis,

but tilted away from it.
“As m the structure is a relatively stiff one it easily

explains the extended shape of the BNA in solution. It is

also consistent with the tttration curve. This has irreversible

features which suggest that the bases are hydroren-bonded
together. However the most striking support for the specific
paifing of the bases comes from the recent analytical data.
These show that for every species so far examined . - and
there are over forty of them suxfax ~- the number of adenines
in some given DNA is closely equal to the number of thymines,
and the number of guanines equal to the number of cytosdnes,
althourh the cross~ratio (between say adenine and guanine )

can vary considerably from species to species. This remakable |
fact, which is exactly what one would expect from a model |

containing only the specific pairs, was first pointed out by

‘Dr. Chargaff. Indeed, Since the Sequence of bases along &
Single chain is believed to be irregular this result is very
dif*icult to explain except by specific pairing.

‘It might be thought that while this model might be correct
for the DNA extracted from the cell and made into fibres the
DNA in the cell was in a radically different fem form. This

Seems unlikely since it is difficult to see how the very charact-

aristic features of the model could he produced merely by

the extraction procedure. However Dr. Wilkins has shown

that it is possible to get very similar X-ray pictures from
intact biological material, such as sperm heads and bacteriophage,
So that there seems little doubt that the structure is

biclogically significant.
The present position is tierefore that while the details
of the structure remain to be worked out - and until this is
done the model cannot be considered as proved -~- it Seems
very vrobable that the following statements will stand the
test of time:

1. The structure consists of two chains

2. The chains are helical and wound round a common axis.

3. They are held together by hydrogen bonds between
specific pairs of bases.

4, The structure occurs in biologically intact material,
8 A nossible replication mechanism

Now the exciting thing about a model of this type is
that it immediately suggests how the DNA might produce an
exact copy of itself. This is heause the model consists of
two parts, each of which is the complement the other. The
basic idea is that the two chains in the structure unwind
and separate, Each chain then acts as a sort of mould onto
which a new complementary chain man be Synthesised. When this
process is complete there will be two pairs of chains where
we only naa one before. Moreover, because of the specific
pairing of the bases: the sequence of the pairs of bases will
have been duplicated exactly.

As an analogy consider two photographic films, one a

positive and the other a | negative of the same scene. Now if
one gives the positive to one person , and asks him to print
a negative from it, and also gives the original negative to
another person, and ask him to print a positive from it they
wills end up with two pairs of photographs, each like the
original pair. We shall, in effect have made an exact copy
of our original pair in one step. oe

To see how this works out in the case of DNA let us consider
the process in rather more detail. Since we have to synthesise
two new chains we rg require some new material. The exact

precursors of DNA are not known, but let us assume for simplicity

that it is built up from nucleotides, which is the name given

to the small tholecules which contain one phosphate, one surar
and one base.

Imagine,then, that we have 4 single helical chain of
DNA, and that floating around it, inside the cell, there is a
supply of the four sorts of nucleotides. Every now and then
a lose nucleotige will attach itself by its base to one of
the bases of the DNA chain. Now if this happens to two
adjoining pases, and if the loose nucleotides are the type.
woich can form specific pairs with those already there, they
will be in just the right position to be joined together, and,
eventually , to form part of the new chain. If one or both
of tnem is not the correct type to go in at that point it
will be impossible to join tnem together and before long they

will aiffuse elsewhere. Thus only the nucleotides with the

:
with the proper bases will get joined togetner to form the
new chain.

While this process is going on the other single chain of
the original pair will also be forming, in a similar manner,
a new chain complementary to itself. The whole process is
illustrated in figure - diInFig. wa & there is shown

a small stretch of the original pair of chains. In Fiz.

they have separated. In the next figure new chains are being ~

formed from loese nucleotides, and in Fig. the process is
complete, and it can be seen that the original pair has
now been @uplicated.

At the moment this idea must he revarded simply as a
working hypothesis. Straight away it raises a number cf
questions. How do the two chains unwind ? What holds a
Single chain in a helical configuration ? (Watson and I
suspect that the replication starts almost as soon as the
unwinding, 80 that only a very short stretch is ever in the
"single' state at one time). Most important of all, how
does the DNA influence the rest of the cell ? We belteve that
the sequence of the bases along the DNA is the code that
carries the genetical information, but how does it produce
its effect ? We can see how the core may be copied, but as
yet we cannot read it.

In favour of the idea one can only say that it seems
rather an odd coincidence to find in the one material which is

most closely associated with replication a structure of
meee

exactly the type one would need to carry out &@ specific
replication szukeme process, namely one showing both variety

and complementarity. We can only hope that the simplicity

of the idea will stimulate someone to devise some new experiments

which will either prove or disprove it.