タンパク質モジュールの構造と進化に関する研究

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九州大学学術情報リポジトリ

Kyushu University Institutional Repository

タンパク質モジュールの構造と進化に関する研究

野坂, 通子

九州大学理学研究科生物学専攻

https://doi.org/10.11501/3054130

出版情報：Kyushu University, 1990, 理学博士, 課程博士バージョン：

権利関係：

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IV. DISCUSSION

IV‑l The lnsertion or DeleLion of Modulcs 1nむhe Adenylate Klnase FamJly

A case ln which a few modules havc becn cL

む

her lnserted or deletcd durlng protein evolu.tlon 1n adcny18Lc klnasc faml1y Is prescnLcd. From the size distrlbutions of the modulcs and cxons ln sectlon 111‑2， it can be estlmated LhaL Lhe dlscovered segment which has becn lnserLcd Qr de)ctcd canslSLS of LWO or three

modules， and 1t can inferred that thls casc mlght have happened as a result of the lnsertlon or deletlon of onc cxon ln lhe gcnes.

1 '

h15 estlmatlon a150 colncldes w1th the raLlo of lntron poslt.lons and confirmcd module boundarlcs in section LlJ‑4. 1'h15 flnding offers evldence that. ln some stages of cvolution

，

proteins progressed through the strucLural supporL of modules. lt can bc concluded that module structurcs havc bccn gcnerally

conserved

，

but

，

ln some cases， have changcd part of thelr modulc organlzatlons to produce other protelns wlth partlally dlfferent

func tlons

(1) !¥1odules and Slm11ar Segments 1n PorcJnc Adcnylate Kinase FamJly

Thc .Identlfled modules of porcJnc adcnylatc klnasc mlght exp]aln thc lnternal repetltlons of the sequence and structure of

乞he protcJn. Ohonlshl (1988) reportcd thc posslbllJty of sequencc repctltlon wlthin porcine AK

，

where threc scgments 1‑47， 48‑79 and 80‑124 arc somewhat slmllar to onc another as to sequcnce numbcrs 日rune et. a1. (1985) reported that the segments of thc resldue numbers 14‑24， 36‑47， 88‑101 and ]46‑168 match well when

乞hlS enzyme and yeast AK are compared. 1n both cases

，

the

37

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』ーー曹回・・ ^a^且

resldues of the 36‑th. the 47‑th. the lOl‑th and thc 146‑th posltlons are the module boundarlcs. There Is a weak local mlnlmum of CP at the resldue numbcr 79， suggest1ng a posslble module boundary on thc ancestral gcne of AK. It ls notablc LhaL

Lhc othcr poss1ble poslLions of the lar'ge alternation， whlch have bccn assumcd by Lhese sequencc authors， colncLde wlth any of thc oLhcr modulc boundarles. These observ8Llons may lntlmate gene dupllcatlon by a smallcr gcnc whlch had coded the origlnaJ modu]cs of anccstral adenylaLe klnasc

rhc sLmllarlty among somc modules wlthln AK suggests the role of modules in early cvolutlon. It Is lnteresting to compare the module organlzatlon of thc AK to those of the NAD‑blndlng dorr】alnsof some glycolyLlc dehydroger

、

ases. These enzymes take part ln the dlffcrcnt hydrolytlc rcactions on the glycolytlc pa thway us Lng a co‑factor. NAD (Nlcotlnc‑AmJdc‑D J.‑phospha te)

Porclne AK and doma!ns of these cnzymes are known to have slmllar pcptldc foldlng (Rossmann， et.a]. 1975). Llgands of AK and thcsc domalns (AMP + ATP and NAD. respectlvely) arc such simllar

molcculcs that Ltlclr tha^乞 substratcblndlng behavlor should be near)y Lhc samc. Although the evolutlonal relatlons betwcen thcm have not becn deflnltely establlshed as yet， a comparlson betwccn these NAD‑blndlng domalns and AK ls lntcrestlng ln ltself (N05aka and G6. 1n preparatlon)

(2) Modulcs and Functlonally‑ImportanL Reslducs of The Enzymc A G‑rlch reg.1on and two othcr conscnsus scgmcnts which arc common]y ob5crved ln ATP blndlng proLclns arc lnLerestlng W.1t tl rcgard Lo Llle modulcs of adenylate klnasc. ScgmcnL 1. from 15 Lo 21 ln the rcslduc nUlnber of the porclne AK， 15 lncluded 1n the

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flexlble loop whJch makes a glant an10n hoJe In the substrate blnd1ng reglon. Thls hole mlght be effcctJvc ln stabl11z1ng thc phosphorous anion of the lntermedlatc rcactlon (Dreuslcke and Schulz. 1986). All res1dues of segment 1 cx1st 111 module 2 and those of the second segment (resldue numbers 27‑31) arc jn modulc 3. 1.'CSpCC t .1vely. On the other hand. fou r rcs1ducs 0 f thc th i

，

^"^d

segment al"C 1n the module 10 and two rcs.lducs al'e 1n the modulc 11. Thus. 1t Is suggested that funct10ns of thc former two

segments lIlay be dlfferent from the functJon of the latter segment

lt 1s 1nterestlng that the other funct10nally Jmportant resldues sometlmes exlst near module boundarles. Thls phenomenon 1s commonly observed ln several protelns studied up to now，

Thcreforc. lt m1ght suggest the mechar

、

Jsms of the enzyme funct.lon dependlng on the respectlve structures of modules

IV‑2 Module S1

ヌ

C

Thc slze distrlbutlon of lIlodulcs shows the domlnance of thetr unlversalJty over the bas1c categorles of species.

prokaryotcs and eukaryotes. Th1s suggests that modu1es exlstcd before the d1vergcnce of prokaryotes and eukaryotes. Furthermore.

thelr dJstrlbution 1s consistent wJth thc s1zc distrlbutlon of exons. 5mall exons 1n the d1str1butlon are the same as small modules as to thclr slze dls乞r1but1on. and largcr exons could be

regarded as the summatlon of 5maIl segments which codc connected modules. Thc most abundant exons seem to codc a pcptlde

conslstlng of about three modules. Thus. the hypothcsLs that smal1 exons whlch code modules had conjugatcd together dur1ng evolut1on to produce a 1arger exon5 15 5upported

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』ーー『園圃』 ^畠

Thc average length of these modulcs Js 15 rcsJducs. and thc most1y common module size 1s 13‑14 residues. lt Is Lnteresting to conslder the coincldence between modulc slzc and thc slzes of po1ymcrlzed peptides and nucleotldcs， whlch are syntheslzed undCI thc model conditions of the primodial earth. Yanagawa and lto (1986)， obtained amino acid po]ymers of ]000‑4000 da]ton

(molecular welght). These pOlyrncrs havc bccn produccd by repcatlng a hydratjon‑dehydratlon cycle of solvents wh1ch contalned alanlne. glycine

，

vallne

，

and aspartlc aclds. These amJdes are be11eved to have been synthcstzed from carbon hydratcs and somc nltrogcnous materials 1n the chemlcal cvolution of the ear11est stage. A1though al1 of these polymcrs are not peptides.

abouL 80 percent of them possessed thc pcpLlde bonds. ConslderLng that Lhc molecular welght of these amlno Bcld Is about 100

dalton. the sizc of thcse peptides are assumcd Lo bc frorn 8 to 36 rcslducs. Since the peptide bonds would noL be necessarl1y

contLnuous. the rcal peptides inc]uded 1n polymcrs mlght be srna11er than thls estlmation. Nevcrthelcss. 1L 1s cxcLting that thc cstimatlon of anclent peptldc slzc colnc.ides exactly with Lhc lengths of contemporary modu1es. The succcssfully‑connected and strucLurary‑stable part of these polymers should. thcrefore， corrcspond to thc orlglna1 materlal of modules

。~odulc slze a1so coincldes wlLh Lhe slze of nucleotide polymcrs. Accvcdo and Orgel (1986) showed Lhat polynucleotlde 1ength which could form ln primitlve cond1tlons wus at most 60 molcculcs. correspondlng Lo a peptLdc of 20 amjno aclds. Thc colncldcncc of module slze both to the nucleotlde polymer 8nd Lo the syntheslzed peptldes may suggest that modules might have

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somcthing to do w1th the lntcract10n of pePtlde and nucleotide durlng early evolut10n

There 1s also a proof that a contemporary pcPt1de

。

^{f 20}^res1duescan ex1st 1n a stablc cond1t10n 1n an aqueous s01ut10n. Rlbonuclease 5

，

wh1ch 1s prcparcd from the subt111s1n digestlon of ribonuclease A. cons1sts of thc 5 peptidc and thc S proteln. This S peptide， which 1s N‑tcrmlnal scgmcnt of 20

res1dues， can form a hel1x slructure tn aqueous so1ut10n (Shoemaker et. al.

，

1987)

Thcse cxper1ments and observatlon suggest thal the posslble peptldc length 1n early evolution was aboul 20 residues and 1..hat.

1n spcc!aJ cascs

，

somc pcptides whlch were shorler than 20 resJducs could cxlst ln an aqueous solvenl

IV‑3 Modules and the Secondary 5truclurcs of ProtcLns

Two corrclat10ns betwecn modules and sccondary structures arc found. 1. Module boundaries oflen occur on the βslruclures 2. Avcragc s1ze of modules ln a proleln sccms to dcpcnd on the he11x rallo of lhe proleln. These resulls suggesl lhat some sccondary slructures provlde modu]es w1lh bas1c slruclural

supporl. Module boundar1es seems to relnforce their connect10ns by form1ngβstructures ln thc lnner reglon of prote1ns. wh1ch may also assist benefit for modules lo move or lo react

cooperatlvcly. Thus， a helix allows modules to en]arge ttle1r slzc. to have r1gid structures and to movc dynamlcally

(1) The Preference for βstructurc on Module soundarJes

1t can be thcorlzed that β s tructures cxlstIng on module boundarlcs m1ght enforce the 1nteraclIons betwccn modules

41

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suppos1ng Lhal modules wllhln a proleln are connccled and lhal the boundar1es formβ‑structures， lhe connecled modules couJd v1brale and acl together， lntroduclng a wlde range of

cooperallvlty as to protein functlons. secause lhe encrgy levc]

of each sccondary structure 1s not so dlffcrcnl， secondary slruclures of module boundarlcs mlghl have changed rapldly

accordlng Lo thc functlonal reflncmcnl or djvlslons of protcins Thercfore. lhls correlatlon could be assumed lo havc dcveloped and lo havc bccn conserved durlng prolcln cvolullon

(2) The lIellx l~atlo and Cornpresslbl1llY of Prolelns

Slnce a hclix enforce the stabll1ly of each module and cnlarge Lhc modulc size， lt Is hYPOlhcsizcd lhal proleins of

larger modulcs， ln their funcむjon81 mOlion， would change lheit forms more sharply and simply than would proteJns of smallel modulcs. For example， il may be easy to observe the reacLive

mOllon of hemoglobln， which 15 a hlghly hcl lx‑r lch protcln. Thcl'c Js one very interestlng cxample of tllls posslbll1ty

Thc compressiblllty of a protcJn， whlch reflects its

hydrat[on and lhe void effect5， 15 ca)culatcd by mea5urlng the translatlon ve]ocity and the v1scoslty of a solvent contalnlng thc proleln. Allhough it Is dlff1cull LO measurc the void cffecl dlrectly， lhls cffect can be esllmaled by an approxlmatlon whJch Ls conflrmed to flt the experlmental results of several prolelns Gckko ct. al. (1984) detcrmlned the vold effect of protclns from

thelr compresslblllty and ob5crved the tendcncy for the effecl to increase In proportion to the helLx ratlos of protelns. SUPPo51ng that therc 81"0 two types of modules， Lhe largcr bclng morc ri.gld and the smaller being softer. the vold of a proteln consls乞lng of

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thc fOl'mer modules would be large 'rthan the vold of a proteln formed from the latter modules^，Therefore. the hellx ratlo of protelns and. accord1ngly of modules would bc 1mportant to the dynamlcs of prote1ns^，Th1s 1s conslstent wl1h 1he prospect dcrlved from 1he correlat10n between he11x con1ents and the average sJze of a proteln module.

lV‑4 ^ Sla1lst1cal Exam1nat10n 01' 1hc Corrcspondence be1wccn Module

日

oundar1esand lntron Pos1110ns

1'he correspondence between module boundarles and lntron pos11ions is conf1rmed by numerlcal examlna1Jon. ThJs Sludy verlflcs that module boundarles have a strong correlatlon wlth thc locat10n of lntron. However. 1乞 1s suggested 1ha1 evolutlonal altcrnatlon has occurred ln the modules of some con1emporary

protclns. for there are some lntrons whlch do not correspond wc]l 10 rnodule boundarles.

^ssurnlng that the reflncd mcthod 15 approprlate enough for modulc lden1lfication. there would secm to bc somc altcrat10ns to

Lhc correspondence. Three possJble explanatJons for th15

phcnomena are as follows: 1. Somc modules have changed by fus1ng so tha1 they 8re no longer indepcndent modules. Nevertheless. the introns have rema1ned for some reason. Jt sccms probable thaL thcsc modules have changed dur1ng evolutlon as the rcsult of

de]e1lons of several amino acids. whlch are generally observed ln protcLns. If th1s 1s the case. the traccs of thc anclcnt modulc boundarles would rema1n on thelr structural fca1urcs (CP) and Lhe poslLlon of 1hese traces would be rclatlvely dJstant from any of Lhe ldcn1Lfled module boundarles. Thereforc. 1t mlght be bettcr to recognlze these traces as module boundarJes. acccPtlng Lhc

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11mltatlon of the contemporary method. 2. Somc lntrons have movcd slighLly durlng evoluLlon shlfLlng from thelr orlg1nal posltlons Thc devlatlon between thc lntron posltlons and thc corrcsponding modulc boundarles would be small jn this case. Thus， relat1vcly smal1 dcvlaLlon should be accepted. 3. 50me of less corresponding lnLrons emcrgcd by movable clemcnts. Thesc lntrons ml，ght be

Jnsertcd lnto the genes without any correlatlon to the modules 1I0wever， the lnsertlon of introns can not be asslgned as long as

lL has no effcct on proteln structures. Thercfore. thls last possJbllJty should be employed only ln the event the flrst

posslbll1ty can not explaln thc largcr devlaLJon. lf Lhis case ls asslgncd as thc real lncldent， thc mcthod and the process of

modulc ldentlflcation should be lmprovcd. Tlle appl1cabl1lty of thesc thrce posslbl11ty to dJfferent lntrons and thelr relative domlnance C8n not bc detcrmincd from any of thc aval1able data lIowcvcr， somc dJ fCcrenccs among these aJ.teratlvc cxplanatlons would bc distlnguished based on thc above consideraLions

，

^'^h^ealternatlons of modulcs lnferred ln thJs study seem to havc happcned in rClativcly later sLages of proteln evoluLion

These alLcratlons dcpend on thc dcletion or the InserLion of small numbers of amino acids for the sake of Lhe reflnernents of proLeln

funcLlon and/or its specifications. AnalY51s of these inLrons wlth regard to thls correspondence might g.lve a c]ue to the mcanlng of lntrons

The Origln and Meanlng of Jntrons

Whcther or not the origln of lntrons can be traced back to thc bcglnnjng of l1Ce Is stl11 an unre501ved questlon; however，

thcrc 15 evidence that some introns cxlstcd bcCorc a proteln

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~

ー

codlng gcnc bccamc a contemporary struc.turc. A good eX8mple is Trlose phosphatc lsomerasc (TIM)， whlch 15 an essenLial enzyme of organlsms and Is highly conserved among varlous spccies

(Marchlonnl and Gl1bert， 1986， Gllbert.. cL. 81.. 1986). TIM gene has elgh. tlnt.rons 1n malze. slx introns ln chlckens and humans.

8nd fjve In.trons ln asperglllus nldulans (ycast.). 1'he slx in.tron poslLlons of anlmals are coinclde LO sJx of .the malze lnt.ron poslLlons wlthln a t.hree resldue devlatlon. Three of Lhe flve intron posl.tlons ln yeast are siml1arly colncJde Lo thrcc of thc eJght jnLron positions 1n maize. whlle. .the ot.her tWQ are no1..

conscrved in hlgher cukaryotes. Those lnt.rons whlch are common throughouL the genes from differenL spccies suggcSl lhc loss of lnlrons during Lhe evolution of thls cnzymc. The conscrved

lntrons of '1'1M among a wide rangc of spccies und thc

correspondence between intron5 and structurary unlLs suggesL that m05t of 1ntron5 are fairly old evcn though wc can noL deftniLeJy assJgn the t1附e before the d1vergence of prokarYOLCS and

cukaryotc5

InLeresL1ngly， lntrons of TJM supporL Lhe modulc hypothcsls Gllbcrt. ct.al. (1986) pointed ouL thc slzc unlformlLy of exons

In TIM. FurLhermore. Jntrons observed ln the N

八日

(nlcotlne amJdc adcnlnc dl‑nucleotide)‑binding domaln of TIM gene clcarly djv1de

the lnLeracLing regjons into adenine rlbose and nlcotlnc amlde molctles of NAD. wh1ch 1s conserved also In thc gene of alcohol dehydrogenase (Quigley， et.a].. 1988). Thcsc arc consJstent wlLh

Lhe repeLILJon and alteration of small segmcnts. or modulcs. ln adcnylaLe klnase. It can. therefore. be concluded that lntrons exlsLcd bcfore the essentlal enzymc of llfc was produced on

45

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earlh

The most basic explanation of inlrons can lnfer thal lntrons may accommodale lhe timlng of PCPlldc fOldlng oC modulcs because

intron posll1ons correlate wllh slructurary compact unlts， or modulcs. Thus. inlrons would contrlbute to lhc corrcct folding of a whole prolcln. 1'0 dlscuss the mean1ng of lnlrons. Il i.s a1so ncccssary to lake lnlo considerat10n rlbozymes. whlch cxlSl ln somc klnds of lntrons (Ceck. 1986). Thesc nucleoLJde segments acl as calalylic enzymes for the exci.sJon and lhc ] Inkage of rJbonucleotlde bonds (self‑splicing). Allhough lheir enzymat1c cCflc1ency Js relatLvely low. ribozymcs could have funclloned indcpcndcntly 1n the pr1modlal world as 1s hypothesized ln lhe RNA world of early evolution (Woesc. 1981. 1983); a hypothcsls that rlbonucleotldes were able to repllcale lhemselvcs wllhoul any help from protelns. 1'here mlghl be somelhlng slm11ar funcllon ln lntrons of higher eukaryotlc gcncs. For example， sma11

polypcPtJdcs or pOlynucleotjdes whlch control thc dcgree of gene cxprcssJon or the switch of alternatJve spllclng mlght be coded ln the genes. It would be an important stlmu]us to gcnetic

stud1es to lnvestigate the delicate relat10nships between lntrons and the tertiary structures of proteins

IV‑5 Thc Evolutlon of Proteins sased on Module Struclures

Two types of the al tera tion， small changes and large

changes. have been identified 1n the evolUlLon of modules. Sma1l a1じeratlons.whlch occurrcd wlthln modu]es and wcre caused by thc delctJon or thc lnscrt10n of several amlno acLds. are presumably neccssary for the rcf1nemcr】tof proleln funcl1ons. Il seems to have happencd rclat1vely recently ln proteJn evolution because

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the dlffcrences are small. Large alternatlons. which occurred in module organlzation and are caused by thc delction or thc

lnscrtlon of modules. may depcnd on the tjssue speciflcation of proteln funct10n as 1n the case of adenylate k1nase. Th1s

incidcnL would occur in a relatlvcly early sLage of proLe 】n evolULJon. Thc oldest cvolutlon of modules. Lhe shuffling of

small exons， would have taken place Lo pcrmlL Lhc creaLlon of new funcLJona] protelns

Jmprovement of Automatic Module IdcnLJfJcation

AuLomaLic ldentlflcatlon has becn proved to be probable ln the analysis of sLaListlcal stucties. lIowcver， somc polnts stilJ rcqulre lmprovements lf thls method 1s to dlscuss dlscuss

lndivldual proteins in detail. A morc carcful lnvestlgatlon of these points would be necessary for the accompllshmcnt of this obJectlvc. The following questlon Is to bc rcsolvcd; lIow can

thc module boundaries be selected among a numbcr of nelghborLng candldates from the centripetal proflles. A further 1mprovcmcnl of thls melhod would permi乞 the proper analys!s of

protcln cvolution at its earllesl stages

47

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V. Acknowledgments

The author would 11ke to express her card1.nal thanks to Dr ILlrotsugu

! ' 1

a tsuda. P'"ofessor of Mathema tlca1 s lology a l KyuShu Unlverslty. for hls many useful suggcSllons. helpful advlcc. and conlinuous cncouragcment during her docloral program. Sjnccre lhanks must be cxprcssed to Dr. Mlllko Go. Professor of Blology al Nagoya UniversllY， for lntroducing her lo lhe study of p

，

"oteJn slruclure and lts evolutlon

，

and for dcmonslrallng lo her the lmporlancc of good presenlatlons and many olher aspec.ts of

sclcnt.lflc rcsearch during her cxclting courses. Thc aulhor would llkc .to .thank Drs. Takashl Miyala. Yoh Iwasa. Masaru Ilzuka.

I

ミ

elko KJkuno. Akira Sasakl， 1I1rok 1. lnutsuku. 1I1denot'1 lIayashlda.

Toshlyukl NogUll， and lIaruo Abe for lhclr sllmu.lat.lng dlscus510n5 and encouragemen.t. She a150 .thanks her comrades

，

Nobuo Tamachl，

Kel‑lchl Kuma， A.tsushi Yamauchl， Naoyukl Iwabc， Kuzunorl Sato.

Shlrou Tomoda. and Yulchi KawanlshJ， dS wcJl as many friends， fOI lhelr uscful comments and encouragemenL. Thc author grcatly

t

.hanks John R. Anscomb‑lino， A5socJalc Professor of the Center of Languages and CulLures at Kyushu UnJvcrslly. for hls efrcctlvc lectures on English writing skills and for hls klndly correcllon of thls lhesls and lots of uscful suggesllons .to ll. Some of the compuler programs used in these studles were wrlLten by l】rs

MILlko Go， Nobuhiro Go， Sanzo Mlyazawa， TakashJ Gojるbori， Iliroshlge Mlzuno. Aklra Sasakl，阿rs. Izumi Oda， and Shjrou Tomoda. The author thanks them for permJtLlng her Lo use these programs. Flnally. she humbly dcdlcale thls paper Lo her faLher，

Susumu Nosaka， who dled October 30th， 1990， as an expression of her endurlng appreclation for hls generous klndness and help throughout her educatlon

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VI. REFERENCES

Acevedo^白 O.L. and Orgel. L.E.， NaLure 321・790‑792. 1986 srune

，問。.

Schurnann. R.. Wittlnghofcr. F.，

NucleJc AcJds I~esearch 13: 7]39‑715J. J985 Ccck. T.. Cell 44: 207‑210. 1986

Dayhoff

，

M. 0.， lIunt

，

L. T.， McLaughlln P. J. 8nd Jones

，口口，

At]as of Proteln Sequence and StrucLure

，

ed. Dayhorr

，

M.O Vol.S. pp.345‑352. 1978

Dreuslcke. D.. Karplus. P.A.. Schulz， G.E..

J 。阿01.日101.. 199: 359‑371. 1988

日rcusickc. D.. Schulz

，

G.E.. FEsS LeLL.. 208: 301‑304

，

1986 Egner

，

U.. Tomassclll. A.G.. Schulz. G.E..

J. Mo]

日

101. 195: 649‑658. 1987

Frank

，

R.， TrosLn. M.. Tomassclll. A.G.， Schulz

，

G.E.， Schlrmcr.

R.II.. Eur. J

日

iochem. 141: 629‑636. 1984

Gekko. K.. 日lophyslcs. 日lophyslcal socLcty of Japan

，

24: 466‑471.

1984 (Gekko

，

K. and Noguchi， 11.， J. Phys. Chem.， 83: 2706 2714. 1979)

Gl1bcrt. W. Why genes 10 pleces

つ

NaLure 271: 501. 1978 Gl1bcrL. W.. Machlonni， M. and McNlght. G

CcJl 46: 151‑154. 1986 Go. M.. Nature 291: 90‑92. 1981

Go. M.. PrQC. Natl. Acad. Scl. USA 80: 1964‑1968. 1983 Go. M.. ^dv. siophys. 19: 91‑131. 1985

Go. M.. Nosaka

，

M. eds. Cold Sprlng lIarbor Symposia on

日l010gy. Cold Sprlng Harbor. Ncw York

，

The CoJd Spring l

Iarbor Labora .tory. LII: 915‑924. 1987

Gott. J.M.. Shub. D.A. and selfort. M.， Cell 47: 81‑87， 1986

49

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Hawklns. J.D.， Nucleic Acids Research 16: 9893‑9916. 1988 Ilell. A.， ¥11uller， G.， Noda， L.. Plndcr. 1'.. 5chlrmer. R..

5chlrmer， 1. Von Zabern， 1.，

Eur. J. Biochem. 43: 131‑]44， 1974

lIe'l dt， 11. W.， 5chwalbach， K.. Eur. J 日Jochem. 1: 199‑206. 1967 Jensen， E.O.. Paludan， K.， lIyldlg‑Nlelscn. .LJ.. Jorgcnsen. P

and Marcker. K.A.， Nature 291: 677‑679. 1981

Jukes. 1'.11.. Cantor. C.R.. In: Manmmalian Proteln Mctabolism

l

'1unro. II.N. ed.. Academlc Press. New YOl'k， pp2J‑132. 1969 Klshl. F.. Maruyama. M.， Tanizawa. Y.. Nakazawa， A..

J. 8101. Chem. 261

，

2942‑2945. 1986 Klshi. F.. Tanizawa. Y.. Nakazawa. A..

J. 日101. Chcm. 262

，

11785‑11789. 1987

Kuby. 5.A.. Palmleri， R.II.， Frlschat. A.. Flschcr. ^.II.. Wu.

L .11.. 1'1aland， L.. Manshlp. 何

日Jochcmistry 23: 2393‑2399. 1984

Lec. W.II.. Proc. Natl. Acad. Scl. USA. 78: 1085‑1089. 1981 MarchlonnJ. M. and Gl1bert. W.. Cell 46

，

133‑141. 1986

Matsuura. S.. Igarashl. 1¥1.. Tanlzawa， Y.， Yamada. M.. Klshl. F Kajjl， T.， Fujii， H.， Miwa， 5.

・

Sakural. M. and Nakazawa. 八

J. 8101. Chem.. 264: 10148‑10155. 1989

l

'Hyazawa. S. Gる，阿 .In: the report of PSPCS group 1n Grants‑ln Ald for Spcclal Projcct Rcscarch from thc Mlnlstry of

Educatlon. V: 17‑43. 1981

Noda， L.， In: The Enzymes. Voyer. P.D. ed. 3rd

ed. Acadcmic Press New York and London. VIll: 279‑305. ]973 Naora， 11. and Deacon， N.J

Proc. Natl. Acad. 5cl. US^. 79: 6J96‑6200. 1982

(16)

~aora. 11.. Jl.l1yahara， K. and Curnow. I~.N

Proc. Natl. Acad. Sci. USA

，

84: 6195‑6199

，

1987 Ohonlshl， K.. Biophyslcs. slophyslCal SocleLy of Japan

28: 5‑138. 1988 (Origins or L1fe. 16: 247‑248. 1986)

Pal. E. F.， Sachsenheimer. W.. SchLrmer. R. 11.. Schulz. G.E.. J. Mol. 8101. 114: 37‑45. 1977

Povey. S.. Slaughter. C.A.. W1150n. D.E 白 Gormlcy. r.p.. BuckLon.

K.E.. Perry. P.

，

and sobrow. M

Ann. lIum. Genet.. Lond. 39: 413‑422. 1976

Prova. K.. Toma55clli. A.G.. Nlelsen. P. and Schulz. G.E Nucleic Aclds Res.. 15: 7187. 1987

QuJgley. F.. MarLln. W.F. and Cerff. R

Proc. NaLl. Acad. Scl. USA. 85: 2672‑2676. 1988

Reuner. C.， lIab1e

，阿 .

Wl1manns， M.. Klefer. E.. Schl1LZ. E. and Schulz. G. E.. Protein Seq. Da La ^nal.. 1: 335‑345. 1988 Schulz. G.E.. SchllLz， E.. Tomas5clll.

八

G. Frank. H.. Brune

白川。

WILLlnghofer. A.. and Schlrmcr

，

ILII Eur. J. slochem. 161: 127‑132. 1986

Schulz. G.E. ed.. Cold Sprlng Harbor $ympo5Ja on QuanLiLaLlve

日lology. Cold Sprlng Harbor. New York. The Cold Sprlng lIarbor LaboraLory. Vol. LII: 429‑439. 1987

Shocmaker. K.R.. Kim. P.S.. York. E.J.. SLewart. J.M. and

日

aldwJn.H.L.

，

Nature 326: 563‑567. 1987

Shows. 1

日

.srown. J.A. CytogeneL. Ccll GcneL. 14: 421‑425. 1975 SumlnamL. Y.

，

KlshJ. F.. Torlgoe. 1 白 Nakazawa A

J. 日lochem. 103: 611‑617. 1988

TaJll11a

，

F.. Ncl. M.. J. Mol. Evol.]; 269‑285. 1984 TomasseJJ 1. A.G. and Noda. L.II

51

(17)

ハU

︒

︒ 円巳

1のひ

0 Z 6

・

L 8 I 1 9

QUEt‑‑

4 h

一

c

・

司L P 3 0 0

00ハU

A

‑ 1 ' q d

R 3

qd

︽u

n u ' q d

司ム

bM

nn

: a 2 m r o

e p r q 4

ιh H

c ' S

0・r

i c e

n υ

・

' i W

A L

e e

J 1 1

百' e a

r l B

u e p ι

円巳

Qd pr

s

a m 0 1

Tomasselll，

A.G.， Mast， E.， Janes， W.， Schl1LZ. E

Eu

r. J. Blochem. 155: 111‑119. 1986

Van Cong， N.

. Rebourcet. R.， Wei.l. D.，

Coul . l11n

， P lIors. ~1.-C. . Jami. .J.， Frezal. J

Cy

L

oge

n

eL

. Cell Genet. 13: 113‑118， 1914

Von Zabern. J.. WiLLmann‑Liebold. 日 . UnLuchL‑Grau. R.， Schirmcr.

R. H.. Pal. E. F.. Eur. J. Biochem.

68:

281‑290. 1976

Wj

e]a

nd. 自 . Tomasselli. A. C..

Noda

， L. 11.. Frank. R.. Schulz. G.E..

Eur.

J 日lochem. 143・ 331‑339.1984

W

oesc

.

C.

R. ArchaebacLerla. Scl.Am. 244(June): 94‑106. 1981 W

oesc

.

C.

R. 1n: Evolutlon fr

om Molccules Lo Man..

s

enda

ll. D.S

ed..

pp 209‑233. 1983

Yanagawa 11. and Ito. 問。 Vlva OrlgJ no 15: 11‑28. 1986

Rossrnann. M. G.. Llljas. A.. 日randcn.

C. ‑

J.. l3anaszak. L. J.， 1n: Thc Enzyrnes. Voyer. P. D. cd. 3rd. cd. AcademIc Prcss

New York and Lond o

n. XI: 61‑101. 1915

Go. M.. Nosaka. M.. PROGRESS 1n CLI

N

ICAL and s10LOGJCAL

RESEAR

C I I .

I~ein ， R.， and Golombek， A.

cds.. Nc

w York. Alan R Liss. Inc.. 289: 21‑31， 1989

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Table 1: Universal genetic codon table and the grouping of amino acids de

田

ndingon nucleotide species of the second codon

Second base U

c

^A G

First base

UUU UCU UAU UGU

U UUC Phe UCC UAC Tyr UGC Cys UUA UCA UAA te .r UGA ter UUG Leu UCG Ser UAG ter. UGG Tro

CUU CCU CAU CGU

C CUC CCC CAC His CGC

CUA CCA CAA CGA

CUG Leu CCG Pro CAG Gln CGG Aro

AUU ACU AAU AGU

A AUC ACC AAC Asn AGC Ser AUA Ile ACA AAA AGA

AUG Met' ACG Thr AAG Lys AGG

如

g

GUU GCU GAU GGU

G GUC GCC GAC Asp GGC

GUA GCA

GAA

GGA

GUG Val GCG Ala GAG ωu GGG _G~

• initiation codon

U g r o u p ; F ， L ， 1 ， M ， V C g r o u p ; S ， P ， T ， A

A g r o u p ; Y ， H ， Q ， N ， K ， D ， E

G g r o u p ; C ， W ， R ， S ， G

(19)

Ta

刷

e2: Identity(

悦)

(Iower) and

∞

mpared residue numbers (upper) between each pair of ten sequences. AK3B and AK2B are the enzymes in matrix and inter membranes of

回

vinemit

自由

ondria.AKY is AK in yeast cytosol and AKE is in E. Col .iAK1F

，

AK1C

，

AK1R， AK1P， AK1B and AK1H are AKs of musde cell cytosols of ca巾， chicken， rabbit， porcme

，国

vineand human， respedively

AK3B AK2日 AKY AKE AK1F AK1C AK1R AK1P AK1B AK1H AK3日 189 190 185 185 185 185 185 185 185 AK2B 36.3 190 189 189 189 189 189 189 189 AKY 37.9 54.2 190 190 190 190 190 190 190 AKE 36.0 43.9 38.4 185 185 185 185 185 185 AK1F 29.3 35.3 31.1 36.2 185 185 185 185 185 AK1C 29.3 35.8 31.6 34.6 79.5 185 185 185 185 AK1R 28.2 34.7 30.5 34.6 74.6 87.6 185 185 185 AK1P 28.2 34.2 30.5 34.6 76.2 87.0 94.6 185 185 AK1B 28.2 34.2 30.5 34.0 73.5 85.4 97.8 95.7 185 AK1H 28.2 34.7 31.1 33.5 74.6 85.4 95.1 95.7 96.2

(20)

Table 3: The list 01 29 proteins which are globular and smaller than 200 residues Sixteen 01 these proteins are Irom eukaryotes， twelve are lrom p.okaryotes， and one is Irom the phage 01 prokaryotes

CODE NAME SIZE ORIGIN

3ADK ADENYLA TE KINASE 194 PORCIN 3CPV Ca‑BINDING PARBALBUMIN 108 CARP

1CTX COBRATOXIN 71 COORA

2B5C CYTOCHROME‑B5 93 BOVINE

1HMO HEMERYTHRIN 113 SPINCLlD WORM 1REI IMMUNO GLOBULlN 107 HUMAN

1LH4 LEGHEMOGLOBIN 153 YELLOW LUPIN

6LVZ LYSOlYME 129 CHICKEN

1NX

日

POSTSYNAPTIC NEUROTOXIN 62 SEA SNAKE 2BP2 PHOSPHOLlPASE A=2= 123 BOVINE 1PCY PLASTCYANIN (Cu・binding) 99 POPLAR 2PAB PRE‑ALBUMIN 127 HUMAN 1RN3 RIBONUCLEASE‑A 124 BOVINE 2S0D SUPEROXIDE DISMUTASE (Cu， Zn binding) 151 BOVINE 10VO OVOMUCOID THIRD DOMAIN 56 OUAIL 4PTI PANCREATIC TRYPSIN INHIBITOR 56 BOVINE 4ATC ASPARTATE CARBAMOYLE TRANSFERASE 152 E. COLl

1AZU AZULlN (ELECTRON T

臥

NSPORT) 128 PEUDOMONAS A 156

日

CYTO<コHROMEB‑562 110 E. COLl

3C2C CYTOCHROME ￥C=2= 112 RHODOSPIL

上

UM R 3DFR DIHYROFOLATE REDUCTASE 163 LACTBACILLUS C 1FDX FERREDOXIN 54 PEPTOCOCCUS A 4FXN FLAVODOXIN 138 CLOSTRIDIUM MP 1HIP OXIDIZED HIGH POTENTIAL PROTEIN 85 CHRαAATIUMV 3RXN RUBREDOXIN 52 DESULFOVIBRIO V 2SNS STAPHYLOCOCCAL NUCLEASE 149 STAPHYLOCOCCAL N 2SGA PROTEINASE A 181 STREPTMYCES G 2SSI SUBTILlSIN INHIBITOR 113 STREPTMYCES A 2LZM PHAGE LYSOZYME 164 T4 PHAGE

(21)

Table 4: Comparison between the newly and the originally identilied module boundaries 01 the 29 proteins which are globular and smaller than 200 residues. The number 01 common boundaries is 143， which CQvers 98 percent of the boundaries identified by the distance map method

Method The Number of Module Boundaries Average Size Common Different Total (residues) Distance Map t43 3. 146 19.3

Improved 143 57 200 14.5

• Each 01 them are inciuded in proteins 01 BNL code name; 4ATC， 1 RN3， and 3C2C

，

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