Dogma of Molecular
bY FRANCIS CRICK MC laboraton of Moleculrr
*Gmbrldga ‘ Thr km
The central dogma of molecular biology deals with the detailed It states residue-by-residue transfer of sequential information. that such informatfon cannot be transferred from protein to eitherproteln or nucleic acid. .
csnrtdenblo ovrr-slmplt5cstlon.” Tars quotation is taken fx~m the boginning of an unsigned article* headed “Central dogma revemcd”, recounting the very important work of Dr Howard Ternin’ and others* ahawing that an RNA turnout virus can use viral RNA M tt template for DNA syntheeis. This is not the 5rst time that the idee of the central dogma has beanmisunderstood, in one way or another. In this article I explain why the term was originally introduced, its true meaning, and state why I think thmt, propotiy understood, it is dill 8n id08 of fund8montal importance. The central dogma was put forward’ at 8 period when much of what we new know in moleouler genetics was not established. Allwehadfoworkonworeoer&infrag mentary experimental resuhs, themselves oftenrather uncertain and cmfuaed, and 8 botmdle~~ optimism that the I basic oonoeptr involved were rathor simple and probably much tho same in all living things. In such e situation web constructed theories ten phby 8 IY&]Y useful fn afeting problems olearly and thun guiding experiThi two central conoepts which had been produced, originally without any explicit statement of the simplification beingintroduced, were those of sequential inform&ion and of de5ned alphabets. Neither of these rteps was trivial. Because it WBB.ebundently &uw by that time that a protein had 8 well de5ned three dimension81 struoturn, end that its nctivity depended crucially on this stratum, it was nv to put the folding-up prooer on one side, and p&u&e that, by end large, the peptide oh&n folded it&f up. ThistemporuriIy & the central problem from a three dimensional one to a one dimensional one. It w88 also v to 6rgue that in spite of the miscellaneous list of amino-ecids found in proteins (as then ,&en in uU biochemical textbooks) some of them, such as phosphoserine, were secondary modi5catioy ; and that there was probably a universal set of twenty used throughout nature. In the ssme ,way minor moditlcationsto the nuclei0 a&d bseee were ignored; urecil in ‘ RNA w&r considered to be informationdly
central dogma, anumiatod by Crick In 1958 and thr of molecular biology ever since, is likely ta prove a
analogous to thymine in DNA, thus giving four st&ndard symbols for the oomponents of nucleia aoid. ’ The prinoipal problem oonld then be s&ted as the formulrction of the generel rules for informationtr8nsGr fkom one polymer with a d&red alphabet~t.o~another. Thiaaotddbecomp&IyrepreeMedbythediagramof, Fig. 1 (whioh was aotually ‘ drawn at-that time;> though I &m not mrre that it wus ‘ ever published) in which all pomible sim le transfem were reprwented, by arrfmJ. Thelurowa c& not, of oouree, m@wmt the flow of titter but the direotional flow of detailed, residue-by-residue; sequenaainformation from one polymer, moleoule to ‘ !., 8nother. Now if 811 poesible transfers commonly oceurmd it would have been almost impassible ta.construct useful theorim. Nevertheless, such theories were p&of our everydaydis&sifm~1.This~bec8use~it.w&bGg tacitly atmmed thet oertsin t&m could not ixour: It oeourmd to me that it would be wioe to st+ these vptions explicitly.
‘ 0 DNA
/ / // // 9f ‘ \ 1 \ \RN:’ ; -f ‘ r. ‘ \ ~PRO&J
r’ _’.i A &lo dJ9is. &wd’ th& the &.. &$ :& dividedroughlyintotbree~upe.’ The5riftglwupwM those for whioh some e&denoe; direct or’ indimat, 8BB668d in Fig. 3. toexist.’ These’ arenhownbythesolid~
Theywere: :. : ‘ ;.
I I I I
(a) (b) (a) (d)
DNA-+DNA DtiA+RNA RNA~Protein’ RNAr’ RNAl
/!+i RNA e--PROTEIN _I (>. c).
he Fly. 1. The umm rbor all...