http://genomebiology.com/2000/1/2/comment/1002.

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Comment
Dog eat dogma
Gregory A PeLsko
Address: RosensLIeI BusIc MedIcuI ScIences ReseurcI CenLer, BrundeIs UnIversILy, WuILIum, MA ozqq-q11o, USA.
E-muII: peLskobrundeIs.edu
Published: 28 July 2000
Genome Biology 2000, 1(2):comment1002.11002.2
The electronic version of this article is the complete one and can be
found online at http://genomebiology.com/2000/1/2/comment/1002
GenomeBiology.com (Print ISSN 1465-6906; Online ISSN 1465-6914)
L Is Iumun nuLure Lo InIIuLe one`s Ideus und conLrIbuLIons. L
Is uIso Iumun nuLure Lo Iung onLo one`s Ideus Iong uILer LIey
Iuve ouLIIved LIeIr useIuIness, In mucI LIe sume wuy LIuL u
purenL wIII sLIII supporL u cIIId wIo Ius grown up Lo be u
menuce Lo socIeLy. BoLI LruILs ure uL work wIenever u scIen-
LIsL mukes sweepIng sLuLemenLs. TIe more generuI one`s
InsIgIL or dIscovery cun be cIuImed Lo be, LIe greuLer ILs
seemIng ImporLunce. And IuvIng gone ouL on LIuL proverbIuI
IImb, u scIenLIsL wIII do mucI Lo uvoId concedIng LIuL IL muy
be Iess LIun IL wus LIougIL Lo be, wIIcI Is wIy so muny ouL-
duLed concepLs Iuve more IIves LIun u cuL.
ew sLuLemenLs In bIoIogy Iuve been us sweepIng us LIe
'CenLruI Dogmu oI MoIecuIur BIoIogy`: DNA mukes RNA
mukes proLeIn. Ls nume Is uIwuys cupILuIIzed, IIke LIe Con-
sLILuLIon oI LIe UnILed SLuLes or LIe Mugnu CurLu. L Is
usuuIIy sLuLed wILIouL quuIIIIcuLIon. L wus reIerred Lo, Irom
ILs IncepLIon, us u dogmu ruLIer LIun u LIeory. (Even DurwIn
Iud LIe modesLy Lo cuII evoIuLIon u LIeory.) ScIenLIsLs don`L
usuuIIy produce dogmus; LIuL Is nomInuIIy LIe provInce oI
reIIgIons, und even LIe brIeIesL sLudy oI IIsLory wIII suggesL
LIuL, In uddILIon Lo udmILLIng oI no conLrudIcLIon, dogmus
Lend Lo be uccompunIed by IoLs oI oLIer Iun LIIngs, sucI us
InquIsILIons und wurs.
TIe CenLruI Dogmu wus beIoved oI sLudenLs becuuse IL wus
eusy Lo remember und Iud no sLuLed excepLIons, IIke uny
good dogmu. SudIy, IL Ius IuIIen on Iurd LImes oI IuLe. TIe
dIscovery oI reverse LrunscrIpLuse provIded un InconvenIenL
exumpIe oI LIe synLIesIs oI DNA Irom RNA. An uLLempL wus
mude Lo re-esLubIIsI dogmu sLuLus by expIuInIng LIuL LIe
pIruse 'DNA mukes RNA mukes proLeIn` reuIIy reIerred Lo LIe
IIow oI geneLIc InIormuLIon, noL LIe ucLuuI sLeps oI synLIesIs.
TIen uIong cume RNA edILIng, In wIIcI guIde RNAs or
enzyme ucLIon modIIy some messenger RNAs sucI LIuL LIe
IInuI proLeIn sequence cunnoL be deduced Irom LIe gene
sequence uIone. AILernuLIve spIIcIng dIdn`L IeIp eILIer: IL
couId be urgued LIuL IL represenLs u cuse oI RNA mukIng
ILseII, LIen mukIng u buncI oI dIIIerenL proLeIns. And LIen
LIere wus LIuL InconvenIenL sLuII ubouL RNA cuLuIysIs, wIIcI
suggesLed LIuL LIere wus once un RNA worId In wIIcI RNA
mude proLeIn wILIouL DNA geLLIng InLo LIe ucL uL uII. To
uccounL Ior uII LIIs, LIe CenLruI Dogmu now wouId Iuve Lo go
someLIIng IIke LIIs: 'DNA mukes RNA mukes proLeIn, buL
someLImes RNA cun muke DNA und oLIer LImes RNA mukes
RNA, wIIcI mukes proLeIns dIIIerenL Irom wIuL LIey wouId
be II onIy DNA mude LIe RNA, und once upon u LIme RNA
mude proLeIn, probubIy, buL no-one knows Ior cerLuIn`. Or, II
you preIer your dogmus pILIy: 'DNA mukes RNA mukes
proLeIn, excepL wIen IL doesn`L`.
PerIups IL Is besL Lo reLIre LIe CenLruI Dogmu, und beIore
suggesLIng u repIucemenL remInd ourseIves LIuL, becuuse IL
wus u dogmu, uII oI LIe excepLIons - Irom reverse LrunscrIp-
LIon Lo RNA cuLuIysIs Lo edILIng oI LIe messuge - were InI-
LIuIIy dIsmIssed us urLIIucLs und Iud more LroubIe guInIng
uccepLunce LIun perIups LIey sIouId Iuve Irom LIe quuIILy
oI LIe experImenLuI work. SkepLIcIsm In scIence Is u good
LIIng, buL dogmus breed cynIcIsm (wIIcI Is noL) und Ieud Lo
reucLIonury LIInkIng. JusL usk GuIIIeo.
SLIII, dogmus Iuve LIeIr uses. SLudenLs, us sLuLed eurIIer, IInd
LIem very IeIpIuI. TIey provIde u convenIenL encupsuIuLIon
oI LIe perceIved wIsdom oI LIe momenL. TIey ure usuuIIy
eusIer Ior Iuy peopIe Lo undersLund LIun IuborIousIy quuIIIIed
sLuLemenLs. And LIey provIde u cIeurIy vIsIbIe LurgeL Ior LIuL
mosL InLeresLIng breed oI scIenLIsL, LIe IconocIusL, Lo sIooL uL
- ruLIer IIke poIIcemen`s IuLs. So, mIgIL us weII suggesL
LIuL genomIcs Ius u dogmu LIuL Is more proIound, LIInk,
LIun LIe CenLruI Dogmu, und more robusL Lo booL.
TIe CenLruI Dogmu oI GenomIcs derIves Irom sLrucLuruI
bIoIogy. ConcIseIy sLuLed, IL Is: 'sequence deLermInes sLruc-
Lure deLermInes IuncLIon`. CIuperone-medIuLed proLeIn
IoIdIng does noL vIoIuLe LIIs dogmu, becuuse cIuperones do
noL Induce In proLeIns u IoId LIuL Is dIIIerenL Irom one
2 Genome Biology Vol 1 No 2 PeLsko
udopLed wIen LIe proLeIns ure uIIowed Lo IoId on LIeIr own In
dIIuLe soIuLIon - cIuperones jusL expedILe LIe IoIdIng or
prevenL unwunLed uggreguLIon. PosL-LrunsIuLIonuI modIIIcu-
LIon oI LIe sLrucLure by IImILed proLeoIysIs, pIospIoryIuLIon,
gIycosyIuLIon und LIe IIke uIso does noL vIoIuLe LIe dogmu,
becuuse LIe sequence und sLrucLure oI LIe proLeIn deLermIne
LIe nuLure oI sucI modIIIcuLIons, und LIe sequence und sLruc-
Lure oI LIe proLeIn uILer modIIIcuLIon deLermInes wIuL LIe
consequences oI LIuL modIIIcuLIon wIII be. TIe dogmu Is
vugue ubouL wIIcI sequence Is reIerred Lo, wIIcI Is useIuI
becuuse IL Iorces us Lo LIInk ubouL IL. Upon reIIecLIon, IL Is
cIeur LIuL LIe reIevunL sequence musL be LIuL oI LIe proLeIn,
noL LIe DNA or RNA, und specIIIcuIIy LIuL oI LIe proLeIn IoI-
IowIng uny modIIIcuLIons LIuL muy be mude on LIe puLIwuy
Lo IuII expressIon oI IuncLIon. TIuL Is u very ImporLunL concIu-
sIon, becuuse IL meuns LIe Lusk oI genome sequencIng cunnoL
be consIdered compIeLe unLII genome-wIde meLIods Ior
deLecLIng und cIurucLerIzIng cIunges In LIe proLeIn sequence
Iuve been deveIoped und uppIIed.
TIe dogmu usserLs LIuL IL sIouId be possIbIe, uILImuLeIy, Lo
deduce LIe IuncLIon oI u proLeIn Irom ILs sLrucLure. BeIIeI In
LIe LruLI oI LIIs sLuLemenL IIes uL LIe IeurL oI sLrucLuruI
genomIcs, wIIcI endeuvors Lo deLermIne sLrucLures Ior uII oI
LIe gene producLs In u gIven orgunIsm. YeL Iere LIe dogmu
cun be uccused oI oversImpIIIIcuLIon. ProLeIn-proLeIn InLer-
ucLIons und proLeIn IocuIIzuLIon wILIIn LIe ceII cun Iuve pro-
Iound InIIuence on proLeIn IuncLIon. BuL beIIeve IL Is sound
Lo urgue In rebuLLuI LIuL LIese LIIngs uIso depend dIrecLIy on
LIe sequence und sLrucLure oI LIe proLeIn In quesLIon.
TIe CenLruI Dogmu oI GenomIcs Is u concIse summury oI LIe
busIc ussumpLIons LIuL underIIe LIIs IIeId. TIougI LIey ure
cusL us u dogmu, we wouId do weII Lo beur In mInd LIuL LIey
ure onIy ussumpLIons, uIbeIL ones wILI good Iegs Lo sLund on.
I LIe seeds oI evenLuuI overLIrow ure sown unywIere, LIey
muy be In LIe word 'IuncLIon`. or, unIIke mosL ImporLunL
words In scIence, IuncLIon Is u word wIose meunIng Is IIgIIy
sILuuLIonuI. BuL LIuL`s unoLIer coIumn.