GENETICAL IMPLICATIONS OF THE STRUCTURE OF DEOXYRBONUCLEIC ACID By J. D. WATSON and F. H. C. CRICK Medial Ruearch C&nclf Unit for the Stud of the Molecular structum of Blologlal s llu, cr. wndlsh labmtory, Cunbrl T HE important of deox@~iuoleio aoid (DNA) within living oelb ia undqmbd . It ia found in 811 dividing oell~, lergelJr if not entirely in the nuoIeus, where it is an eesentiel oonetituent of the ohmme aomee. Many lines of evidenoe iadioate that it is tho 08X'Ik Of8 patt Of(ifXlOt ~)thtS@E+Il&iO Spsoifiolty of the ohromommeo end thus of the gene it&f. No. 4501 May 30, 1953 NATURE 965 DNA. - SUCAR /" RASf \ CHOSWATf / BASI - SUGAR \ PHosCHATf / BASE-- SUGAR \ PnOSPHAIt / RA3f -SUGAR \ PHOIPHATf / BASE -sucAR \ PnOSPHAtf /' Flg. 2. Thla tklmt b dlaammmrtlo. The two tlF* boar #rdoltrs the two phaphe- awns ahnlm. and the heri- roaWrodrthspatmdbum holdlog the ahaIm @ether. The vartl~b~laafrlwka ttle IJnt.il now, however, no evidenoe hea been presented to show haw it might 08n-y out the eesentiel operefion required of 8 genetio m8t.43481, that of oxa& eelf&plio8tion. We h8ve moently propoocd 8 etnmturel for the t+aslt of deoxyribonuoleio said whioh, if aorreot, immedi8tely sugBosts 8 meohenitml for its self- tluplia&ion. X-ray evidence obtained by the workem 1st King's College, London*, end presented et the fame time, gives qu8litetive support to our etruoture ad is inoompetible with 8U previously proposed ttt~cturets~. Though the rrtrwtum witl not be com- pkttely proved until e mom oxten8ive aomp8rison AMY been m8de with the X-ray dste, we now feel euffiaient coni3denoe in ita enem1 oorreutneaa to di~30u68 its genetic81 impiio8tion8. &I doing 80 we 8re1 aeeuming th8t fibm of the sslt of deoxyribonuoleio ecrid 8re not 8rtefaota slicing in the method of pwr8tion, ninoerit hae-been ahown by WiIkina 8nd hie oo-workera thst eimih X-rey patterns tue obtsined from both the isolated -&me and o&sin in- biologioel matg~ria~auoh as sperm hesd end b&eriophage . The obmiod formul8 of deoxyribonucleic eaid ia now well estebliahed. The moleuuie ie 8 very long &am, the baokbone of whioh ooneiste of 8 mguhir 8ltem8tion of sugar and phosph8te group, 8a shown in Fig. 1. To eeoh 8ug8r ie 8titaohed 8 nitrogenous Ime, whioh o8n be of four -rent typea. (We have oonnidemd 5-methyl oytosine to be equivnlent to oytoaine, einoe either o8n flt equ8lly well into our stnmtum.) Two of the poeeible -nine end gurmine-8m purinea, end the other two-thymine end aytoeine+~~ pyrimidines. So far aa is knokvn, the ruequem of Beebe 8long the oh8in is irmguI8r. The monomer unit, eonsiating of phosphste, sugar end bese, iS known 88 8 nu&otide. The flret fesfure of our atruoture whioh in of biologioel intenast ie thet it aonsiste not of one ohein, but of two. Theee two ohsine 8re both ooiIed eround 8 oommon fibre exia, 811 ia ehown diegrammetioelly in Fig. 2. It hae often been 8mumed thet mince there was ody one ohein in the chemio81 fOrmd8 them would OLII~ be one ixi the efruotuml unit. However, the density, teken with the X-rsy evidenoe*, Buggeetn very etrongly th8t there ere two. The other biologiaelly importent f&ure ie the menner in which the two oh8ina are held together. This is done by hydrogen bonds between the beaee, as ehown aahem8tioelIy in Fig. 3. The beset JIB joined together in p8irs, 8 single bfm from one ahsin being hydrogen-bonded to 8 eingle bese/rom the other. The important point ie th8t only certain pim of baeea will fit into the struoture. One member of 8 p8ir must be 8 purine end the Other 8 mimidine in odor to bridge between the two &bins. If 8 pair oodated of two purines, for exempIe, there would not be room for it. We believe th8t the b8eea will be prerrent 8ho8t ontirely in their meet probable deutomerio forma. If this ie true, the oonditions for forming hydrogen bonds sre mom restrictive, end the only p8ire Of basea possible 8re : adenine with thymine; gunnine with oytasine. The w8y in whioh these 81~3 joined together is shown in Fige. 4 8nd 5. A given pir 0811 be either w8y round. Adenine, for ex8mpIe, o8n ooour on either ohain; butqwhen it doea, ita partner on the other oh8in mu& 8hvaya be thymine. Thie +iring ie strongly supported by the recent 8d@8l reeulteh, whioh show that for all sources of deoxyribonucleio void eramined the amount of 8denine is olose to the amount of thymine, snd the amount of guenine alose to the Bmount of oytoeine, slthough the oro68-ratio (the r8tio of 8denine to guanino) can vary from one source to another. Indeed, if the sequenoe of ti on one ohei is irregular, it ia difficult to explain them 8nalytic81 cemdte except by the sort of pairing we have Sllgtptd. The phosphate-eugar backbone of our model is oompletaly reg.&r, but 8ny sequenoe of the peire of beses a811 fit into the structure. It follows that in 8 long molecule m8ny different permUtation 8f'e possible, and it therefore seems likely thet the pre~iee sequence of the baeeg is the code whiuh aerriea the gonetic infonnetion. If the 8otueI order of the FIX. 3. chnb, Chemical formula of o @r of dcayrbonuclela aotd The hydrfm'n bOodhN b ~l~bdlwd by dotted llna NATURE May 30, 1953 VOL. 171 0 5' 1 I 1 I Fig. 4. Palrin~ of t&mine and thywine. Hyd?ogcn bonds are shown dotted. One carbon 8tcnn of each sugar le spoWn CUIHH CYTOSlNf Fig. 5. Phiog of guvnlne and cytonine. ahowo dotted. H.ydmgeo bonds are Ooy. c&aoo atom of each sugar b shown basea on one of t,he pair of cheina were given, one izould write down the exact order of the basea on the ot.her one, because of the specific p&ring. Thus one chain is. aa it were, the complement of the other, and it is this feature which suggests how the deoxy- ribonucleic aaid molecule might duplicate itself. Previous discussions of selfauplic8tion have usually involved the conaepb of 8 tempiete, or mould. Either t.he templ8te wea supposed to copy itself directly or it arae to produce 8 `negetive', which in ite turn ~8s to ect 8~ a template and produce the original `positive' once egein. In no case haa it been explained in deteil how it would do this in terms of atoms and molecules. NOW OUT model for deoxyribonucleic aaid is, in affeat, 8 pair of templates, each of which is com- plementery to the other. We imagine that prior to duplictrtion the hydrogen bonda 81~3 broken, and the two oh&i unwind end separate. Eaah ahein t,hen aats BL1 8 tempiete for the formation on to it&f of 8 new aompenion ah&n, BO thet eventually we shall have Cum peits of cheina, where we only had one befom, Moreover, the sequence of the prim of baeee will have been dupliccrted exaatly. A study of our made1 suggetsts thet this dupliaation aould be done ma& simply if the single ahain (or the rdtwmt portion of it) tekea up the helioel aon- flgumtion. We imagine that at this staga in the life of the aell, free nualeotidee, etriatly polynucleotide pnXunrom, 8re Bveileble in qusntity. From time to time the base of 8 free nuaieotide will join up by hydrogen bonds to one of the ba8es on the cldn &eady formed. We now poetul&e thet the polyruer- h&ion of these monomers to form 8 new ahail\ ia only possible if the resulting chain oen form t ho proposed atrnature. Thie is pknwible, beoeueo ~twic reasona would not dlow nualeotidea `arystallizec~' on to the that ahain to epproaah one another in su4 8 way thst they could be joined together into a IIOW ah&n, unless they wem thoee nuoleotidoe which wem neae8e8ry to form our etrnatum. Whethc\r 8 qx&I enzyme is required to a8rry out the polynter- h&ion, or whether the eingle helid ahain aln-:rly formed 8ata effectively 8a en enzyme, mm8ina to he seen. tJmae the two ohaine in our model are intortwilrd, it is ementitrl for them to untwist if they 8n' to separate. As they meke ono aomplete turn arounti eaah other in 34 A., them will be shout 160 trttncl per million moleauler weight, 80 th& whatevur thu preaiae ~NOture of the ahromneame a aonsidcn\ble amount of unooiling would be neaea38ry. It is wok known from micnwroopio observetion thet much coiling end uncoiling oaaurn during mitosis, rrnd t.hough this is on 8 muah Isrger mle it probnhly refleata lliInil8r pmceasee on 8 moleaulsr level. &hough it is difflault st the moment to see how these pmoeeees oaaur without everything getting tangled, we do not feel th8t this objeation will be insupemble. Our stratum, as described', ie en open one. .Thcre is room between the pair of polynualeotide ahminw (see Fig. 2) for a polypeptide ah&n to wind erounrl the same helicsl8xie. It may be aigniAoent thet th dietanae between edjecent phosphor stoma, 7.1 A., is aloee to the repeat of 8 fully extended poiypept ide ahein. We think it prabeble that in the ~perrn h4, and in srtifraisl nualeoprote~, the palypeptide ohain oacupiee this poeition. The reletive we&neaa of the second leyer-line in the publi&ed X-ray piaturMa* ie cmdely comp8tible with mrah 8n idea. The funot ion of the protein might well be to aont.rol the coiling end unaoiling. to a&& in holding 8 eingle pdy nualeotide ahein in a heliaal aonflgurrrtion, or somo other nongpeoifio fur&ion. Our model euggeats possible elplanationa for a number of other phenomehs. For example, spon- t8neoua mutetion m8y be due to 8 beee oaaaaionally ocaurring in one of its lees likely tautomerio forma. Again, the pairing between homologous chmmosomcs at meiosis mey depend on pairing between ape&o bases. We shell dimuse these ideaa in detail else- where. For the mom&t, the genor81 acheme we have @opomd for the reproduction of deoxyribonucleia aaid must be regarded aa speaulative. Even if it in con%&, it is clear from what we heve acid that much ren4n~ to be disaovemd hefom the piature of genct ia duplication can be d&bed in detail. What en3 tho polynuoleotide p mmunmx ? What makea the psir of ah&s unwind end sepetate? whet ie the precise role of the protein t k the ahmnumame one long pair of deoxyribonualeio 8aid ohaina, or does it aorutiet of petohee of the void joined tagether by protein t Despite these uncerteintietr we feel thst our pro- posed struoture for deaxyribonuoleio void msy help to eoive one of the fund8mental biologia81 pmblems- the molewler b&a of the template needed for genot io repliaation. The hypc&eeia we SRI wing ie thst the template ie the petten of IJMJM formed by ono obin of the deoxyribqnuoleio eaid aad thet the geno contains 8 oo&ement8ry~*r of auah @npla@. No. 4361 :May 30, 1953 NATURE One of ~11 (J. D. W.) haa bean sided by 8 fellowship fawn the National Found&On for Infantile Paralysie (2:.&A.). ' \vrImn. J. D.. end CrlaL. F. H. C.. &bra, 17l. 737 (19Rt). . . * Wllkl 7a 196s 1. H. F.. Mdca, A. U.. and Whoa H. R.. &tutu, ln. i40 (INS k IhlMla, a. Pa. and Oallnup, lt, 0.. Nahwu. 1n. . ' (a) .UtbWY, W. T.. 8ymo. h'a. I 8oc. Ex . Bid (M (1947). (b) Furberg, 4 Ada C&b. .Smnd 6, 634 (lOSE$ (e) `ikull~ L and Core ii: B.. .ivatmm,19l.& (1053). PI& OS Nllt'A&..9ef..~;: fi+ (ISW. `(a0 Fmer, It. D. B.`(ln pr&r&uo): ' \Vllklus, M. H. I".. ti lUt&ll. J. `I'.. BiocAim. et Eiophya. &B, 10. 192 (lOs3s). `(`11nM. X.. TO? tiefONU m Inmenhor, H.. Bnwennan. a.. and r%Arlm6. B.. EiacAim. et EiopAua. Ata, a, 402 (1952). 1v.satt. 0. It.. J. Gm. PAmid, 30, Oul (Inbe). 967