The Central Dogma of Molecular Biology: A Retrospective After Fifty Years
The Central Dogma of Molecular Biology: A Retrospective After Fifty Years
The Central Dogma of Molecular Biology: A Retrospective After Fifty Years
Michel Morange
T h e C e n tr a l D o g m a o f m o le c u la r b io lo g y w a s
e n u n c ia te d m o re th a n 5 0 y e a r s a g o b y F r a n c is
C r ic k to d e ¯ n e th e r e la tio n s b e tw e e n th e m a in
in fo r m a tio n a l m a c r o m o le c u le s: D N A , R N A a n d
p r o te in s. S in c e th a t tim e , m a n y d isc ip lin e s h a v e
m im ic k e d b io lo g y , a n d in tr o d u c e d th e ir o w n `C e n -
Michel Morange was
tr a l D o g m a '. T h is a rtic le is a n a tte m p t to r e v ie w
trained in biochemistry th e sta tu s o f th e C e n tr a l D o g m a in th e c o n te x t
and molecular biology at o f th e n e w d isc o v e r ie s th a t w e r e m a d e d u r in g th e
the Pasteur Institute in p a st ¯ fty y e a r s.
Paris. His main interests
are in the history and In tr o d u c tio n
philosophy of science and
the transformation of T h e y ea r 2 0 0 8 w a s th e ¯ ftieth a n n iv ersa ry o f th e p u b li-
biology during the 20th
ca tio n o f a lectu re b y F ra n cis C rick in w h ich h e p u t fo r-
century, in particular the
rise of molecular biology.
w a rd tw o m a jo r co n cep ts: th e C en tra l D o g m a a n d th e
He is also S eq u en ce H y p o th esis [1 ]. T o g eth er w ith D a rw in 's p rin ci-
interested in the emer- p le o f n a tu ra l selectio n , th ese tw o co n cep ts a re b eliev ed
gence of new disciplines to p rov id e th e u n d erp in n in g to a ll o f b io lo g y. T h e 5 0 th
such as synthetic biology
a n n iv ersa ry o ® ers a n id ea l o p p o rtu n ity to re-eva lu a te
and systems biology, the
role of epigenetics and the
th e va lid ity o f th e C en tra l D o g m a .
re-emergence of the
question of life.
W h a t a stra n g e n a m e fo r a scien ti¯ c h y p o th esis! T h e
F ren ch m o lecu la r b io lo g ist J a cq u es M o n o d w a s th e ¯ rst
to rem in d C rick th a t \ A d o g m a is so m eth in g w h ich a
Based on the article entitled ‘Fifty
Years of the Central Dogma’
tru e b eliev er ca n n o t d o u b t" [2 ]. T h is is p ro b a b ly n o t
published in Journal of Bio- w h a t C rick h a d in m in d w h en h e co in ed th e p h ra se. O n
sciences, Vol. 33, pp.171–175, m a n y o cca sio n s, C rick h a s sta ted th a t, a s a n o n -b eliev er
2008. o f relig io n , h e co n sid ered d o g m a s sim p ly a s b o ld h y -
Keywords p o th eses w ith o u t p ro o f. S in ce its in cep tio n , th e C en tra l
The central dogma, chaperone, D o g m a h a s b een rep ea ted ly ch a llen g ed a n d criticized .
evolution, prion, reverse tran- B efo re ex a m in in g th e serio u sn ess o f th ese ch a llen g es, let
scriptase.
u s ex a m in e ¯ rst th e circu m sta n ces u n d er w h ich C rick
1 9 5 3 , sh ow ed th a t it w a s p erfectly a b le to fu l¯ l th e m a in
fu n ctio n a l req u irem en t o f a g en etic m a teria l, n a m ely,
self-rep lica tio n . W h en sep a ra ted , th e tw o stra n d s o f
D N A w ere a b le to g en era te co m p lem en ta ry co p ies o f
th em selv es, essen tia lly b eca u se o f th e co m p lem en ta rity
o f th e b a ses, a d en in e p a irin g o n ly w ith th y m in e a n d g u a -
n in e w ith cy to sin e.
T h e p o ssib ility th a t D N A co u ld d irectly d eterm in e th e
seq u en ce o f p ro tein s w a s p ro p o sed b y th e p h y sicist G eo r-
g e G a m ow in 1 9 5 4 2 . B u t th ere w a s a m a jo r p ro b lem : 2
See article by Vidyanand Nan-
D N A w a s a co m p o n en t o f ch ro m o so m es a n d ch ro m o - jundiah, Resonance, Vol.9,
No.7, pp.44–49, July 2004.
so m es w ere lo ca lized w ith in th e cell n u cleu s, w h erea s
p ro tein sy n th esis w a s k n ow n to o ccu r in th e cy to p la sm
o f eu ka ry o tic cells. In a d d itio n , th is d irect ro le o f D N A
d id n o t ex p la in th e co rrela tio n b etw een th e a b u n d a n ce
o f R N A s in th e cy to p la sm a n d th e ra te o f p ro tein sy n -
th esis. S tu d ies a t th a t tim e h a d a lso sh ow n th a t m icro -
so m es, cy to p la sm ic p a rticles fo rm ed o f R N A s a n d p ro -
tein s, w ere th e p recise p la ce w h ere p ro tein sy n th esis d id
o ccu r. R etro sp ectiv ely, th e D N A { R N A { p ro tein rela tio n
m ig h t a p p ea r a s th e sim p lest so lu tio n to th e p ro b lem .
A ll th e p ieces o f th e p u zzle w ere a lrea d y th ere, a n d so m e
resea rch ers lik e A lex a n d er D o u n ce h a d sta rted to a ssem -
b le th em in th e co rrect w a y.
The Central
h av in g , in m o st ca ses, rela ted , a lb eit slig h tly d i® eren t,
fu n ctio n s.
Dogma has
survived in spite of W h e r e d o e s th e S tr e n g th o f th e C e n tr a l D o g m a
the accumulation O r ig in a te ?
of many new
observations since
I h av e sh ow n th a t th e C en tra l D o g m a h a s su rv iv ed in
its inception.
sp ite o f th e a ccu m u la tio n o f m a n y n ew o b serva tio n s sin ce
its in cep tio n . W h ere d o es its stren g th co m e fro m ? T h e
¯ rst a n sw er w o u ld b e to say th a t it is p recisely th e resu lt
o f th is a ccu m u la tio n o f d a ta a n d th e a b sen ce o f resu lts
o p p o sin g it. In p a rticu la r, n o m a ch in ery th a t is a b le to
co n v ert a p ro tein seq u en ce in to a n u cleic a cid seq u en ce
h a s ev er b een fo u n d . B u t is th is su ± cien t to reg a rd th a t
th e C en tra l D o g m a h a s n ow b een p rov en ? O n e m u st re-
m em b er th a t th e d iscov ery o f ch a p ero n es w a s a n u tter
su rp rise a n d it is im p o ssib le to ex clu d e th e p o ssib ility
th a t co m p lex m ech a n ism s resp o n sib le fo r fu n ctio n s th a t
a re so fa r u n k n ow n rem a in to b e d iscov ered , d esp ite th e
seq u en cin g o f sev era l g en o m es.
A n o th er ju sti¯ ca tio n o f th e C en tra l D o g m a th a t w a s
p o in ted o u t so o n a fter its in cep tio n , a s d iscu ssed ea r-
lier, w a s its clo se rela tio n to th e sep a ra tio n o f th e so m a
a n d th e g erm lin e in tro d u ced b y A u g u st W eism a n n a t
th e en d o f th e 1 9 th cen tu ry, a n d th e a sso cia ted p rin cip le
th a t th e p h en o ty p e ca n n o t sp eci¯ ca lly m o d ify th e g en o -
ty p e. P ro tein s ca n b e id en ti¯ ed w ith th e p h en o ty p e,
a n d th e g en o ty p e w ith D N A . B u t co rrela tin g th e va lu e
o f th e C en tra l D o g m a w ith a n u n d em o n stra ted p rin cip le
is p ro b a b ly n o t a g o o d so lu tio n . T h e sep a ra tio n b etw een
th e so m a a n d th e g erm lin e d o es n o t ex ist in a ll o rg a n -
The Central
ism s. S o , w h ere d o es th e stren g th o f th e C en tra l D o g m a ,
Dogma is simply its \ resilien ce" , co m e fro m ? O n e a n sw er, w h ich h a s n o t
the result of y et b een fu lly ex p lo red , is th a t th e C en tra l D o g m a is
evolution. sim p ly th e resu lt o f ev o lu tio n .
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