1953年沃森和克里克发现DNA双螺旋结构的论文

相关专题

DNA双螺旋结构的前前后后

<center> </center>

我们拟提出脱氧核糖核酸 (DNA)盐的一种结构。这种结构的崭新特点具有重要的生物学意义。

鲍林和考瑞曾提出过一个核酸结构。他们在发表这一结构之前，欣然将手稿送给我们一阅。他们的模型包含磷酸接近纤维袖，碱基在外周的三条多核苷酸 链。

我们觉得这样的结构是不够满意的，其理由有二：

(1)我们认为进行过X射线衍射分析的样品是DNA的盐而不是游离的酸。没有酸性氢原子，接近轴心并带负电的磷酸会相互排斥。在这样的条件下，究竟是什么力量把这种结构维系在一起，尚不清楚。

(2)范德瓦尔力距似显太小。弗雷泽曾提出过另外一种三条多核苷酸 链的结构(将出版)。在他的模型中，磷酸在外边，碱基在内部，并由氢键维系着。他描述的这种结构也不够完善，因此，我们将不予评论。

我们拟提出一个完全不同的脱氧核糖核酸盐的结构。该结构具有绕同一轴心旋转的两条螺旋链(见图)。根据化学常识我们假定，每条链包括联结β-D-脱氧呋喃核糖的3',5'磷酸二酯键。两条链(不是它们的碱基)与纤维轴旋转对称垂直，并呈右手螺旋。由于旋转对称性，两条链的原子顺序方向相反。每条链都与弗尔伯格的第一号模型粗略地相似;即碱基在螺旋内部，磷酸在外边。

糖的构型及其附近的原子与弗尔伯格“标准构型”相似，即糖和与其相联的碱基大致相垂直。每条链在z向每隔3.4埃有一个核苷酸。我们假定，同一条链中相邻核苷酸之间呈36度角，因此，一条链每10个核苷酸，即34埃出现一次螺旋重复。磷原子与纤维轴之间的距离为10埃。因为磷酸基团在螺旋的外部，正离子则易于接近它们。

这个结构模型仍然有值得商榷之处，其含水量偏高，在含水量偏低的情况下，碱基倾斜，DNA的结构会更加紧凑些。这个结构的一个新特点就是通过嘌呤和嘧啶碱基将两条链联系在一起。碱基平面与纤维轴垂直。一条链的碱基与另一条链的碱基通过氢键联系起来形成碱基对。两条链肩并肩地沿共同的之向联系在一起。为了形成氢键，碱基对中必须一个是嘌呤，另一个是嘧啶。在碱基上形成氢键的位置为嘌呤的1位对嘧啶的1位;嘌呤的6位对嘧啶的6位。

假定核酸结构中碱基仅以通常的互变异构形成(即酮式而非醇式构型)出现，则只能形成专一的碱基对。这些专一碱基对为：腺嘌呤(嘌呤)和胸腺嘧啶(嘧啶)，鸟嘌呤(嘌呤)和胞嘧啶(嘧啶)。

换言之。按照这种假设，如果一个碱基对中有一个腺嘌呤，在另一条链上则必然是胸腺嘧啶。同样地，一条链上是鸟嘌呤，另一条链上必是胞嘧啶。多核苷酸链的碱基顺序不受任何限制。因此，如果仅仅存在专一碱基对的话，那么，知道了一条链的碱基顺序，则另一条链的碱基顺序自然也就决定了。

<center> </center>

Nature 原文：

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 other. (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 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 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 other member 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 bery 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 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

The year 1953 could be said to mark, in biology at least, the end of history. Here is James Watson and Francis Crick's paper on the structure of DNA, which ushered in the new era with the celebrated understatement near the end.

(as published in NATURE magazine)