a bacterial sulfonolipid triggers multicellular development in the closest living relatives of...

7/31/2019 A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals

1/16

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http://elife.elifesciences.org/http://dx.doi.org/10.7554/eLife.00013http://dx.doi.org/10.7554/eLife.00013.001http://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfmailto:[email protected]:[email protected]:[email protected]://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/mailto:[email protected]:[email protected]:[email protected]://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://c/Documents%20and%20Settings/0642/Desktop/eLife-121.pdfhttp://dx.doi.org/10.7554/eLife.00013.001http://dx.doi.org/10.7554/eLife.00013http://creativecommons.org/licenses/by/3.0/http://www.elifesciences.org/the-journal/open-access/http://elife.elifesciences.org/


2/16

Of`` ibm`mlr

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sblgc`bgl km`fov`f ~ymevofe ir uhf icoufybc um if O?9H:5GM'>9
http://dx.doi.org/10.7554/eLife.00013.002http://dx.doi.org/10.7554/eLife.00013.002


3/16

Of`` ibm`mlr

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http://dx.doi.org/10.7554/eLife.00013.003http://dx.doi.org/10.7554/eLife.00013.004http://dx.doi.org/10.7554/eLife.00013.004http://dx.doi.org/10.7554/eLife.00013.003


4/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'>>>>>>> C`flcem fu c`' (9>39" !

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5/16

Of`` ibm`mlr

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http://dx.doi.org/10.7554/eLife.00013.006http://dx.doi.org/10.7554/eLife.00013.006


6/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'3>"' Bg cgc`mlr um uhf ohfkmucxbs srsufk mj icoufybc (Jc`af fu c`322838 ! YBJ+3 ~yfsfgu bg fgzbymgkfguc` bsm`cufCUOO 6>838

OK jymk YOC YBJ+3 bs cisfgu bg YOC `bgfs

@bzf C' kcohb~mglmgfgb (of`` ~f``fu" !! YBJ+3 bs ~ymevofe ir C' kcohb~mglmgfgb

Hfcu ab``fe C' kcohb~mglmgfgb (of`` ~f``fu" !! YBJ+3 bs yfsbsucgu um hfcu

C' kcohb~mglmgfgb OK ! YBJ+3 bs yf`fcsfe ir `bzf C`lmyb~hclv

C' kcohb~mglmgfgb OK, imb`fe 3> kbg ! YBJ+3 bs gmu cib`f

C' kcohb~mglmgfgb OK ! ymufbgcsf A ! YBJ+3 bs gmu c ~ymufbg

C' kcohb~mglmgfgb OK ! EGCsf ! YBJ+3 bs gmu EGC

C' kcohb~mglmgfgb OK ! YGCsf ! YBJ+3 bs gmu YGC

C' kcohb~mglmgfgb OK, KfMH fxuycou ! YBJ+3 bs cg mylcgbo omk~mvge

C' kcohb~mglmgfgb of`` ~f``fu, KfMHfxuycou

!! YBJ+3 bs ~yfsfgu bg uhf C`lmyb~hclv of``fgzf`m~f

C' kcohb~mglmgfgb of`` ~f``fu, I`blh+Erfyfxuycou

!! YBJ+3 bs c `b~be

_~hbglmkrf`bg (9> kl k@3" _~hbglmkrf`bg emfs gmu bgevof ymsfuuf

om`mgr efzf`m~kfgu

Kmgmsbc`mlcgl`bmsbef (9> kl k@3" Kmgmsbc`mlcgl`bmsbef emfs gmu bgevofymsfuuf om`mgr efzf`m~kfgu

Lc`coumofyfiymsbef (9> kl k@3" Lc`coumofyfiymsbef emfs gmu bgevof ymsfuufom`mgr efzf`m~kfgu

G+~c`kbumr`+E@+ebhreym`coum ofyfiymsbef (9>kl k@3"

G+~c`kbumr`+E@+ebhreym`coum ofyfiymsbefemfs gmu bgevof ymsfuuf om`mgrefzf`m~kfgu

4 gm bgevoubmg1 !4 `m| bgevoubmg1 !!4 hblh bgevoubmg

OK4 omgebubmgfe kfebvk1 YOC4 ymsfuuf om`mgbfs cisfgu1 YBJ+34 ymsfuuf bgevobgl jcoumy 3

EMB4 3>'>


7/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>' kl k@3", ivu gmu ir jyfsh

kfebvk, C' kcohb~mglmgfgb @^_ (3> kl k@3", ^LG (6> kl k@3", my @^_!^LG' _hm|g cyf uhf |hbsafy+imx

~`mus mj uhf & om`mgbc` of``s-umuc` of``s vgefy fcoh omgebubmg bg uhyff bgef~fgefgu fx~fybkfgus' (I" Uhf km`fov`cy

suyvouvyf mj YBJ+3 efevofe jymk K_ cge 3E+ cge 9E+GKY ecuc' Uhf YBJ+3 suyvouvyf, ?,6+ebhreymxr+9+(9+hreymxr+3?

kfuhr`ufuycefocgckbem"+36+kfuhr`hfxcefocgf+3+sv`jmgbo cobe, hcs u|m ~cyus4 c icsf (shm|g bg yfe" uhcu efgfs

uhf oc~gbgf, cge c jcuur cobe (shm|g bg i`coa"' Jfcuvyfs uhcu ebsubglvbsh YBJ+3 jymk muhfy agm|g oc~gmbes cyf shm|g

|buh om`myfe cyym|s4 uhf 9+hreymxr mg uhf jcuur cobe (i`coa" cge uhf 6+hreymxr mg uhf oc~gbgf icsf (yfe"'

EMB4 3>'>8

Uhf jm``m|bgl lvyf sv~~`fkfgus cyf czcb`ci`f jmy lvyf ?4

Jblvyf sv~~`fkfgu 3' _f~cycubmg mjC' kcohb~mglmgfgb s~hbglm`b~bes ir uhbg `crfy ohymkcumlyc~hr (U@O"'

EMB4 3>'>2

Jblvyf sv~~`fkfgu 9' K_-K_ cgc`rsbs mj YBJ+3'

EMB4 3>'3>Jblvyf sv~~`fkfgu ?' Afr u|m+ebkfgsbmgc` (9E" omyyf`cubmgs mj YBJ+34 Misfyzfe OM_R omyyf`cubmgs'

EMB4 3>'33

Jblvyf sv~~`fkfgu 5' Afr u|m+ebkfgsbmgc` (9E" omyyf`cubmgs mj YBJ+34 Misfyzfe HKIO s~bg srsufk'

EMB4 3>'39

Jblvyf sv~~`fkfgu 6' Afr u|m+ebkfgsbmgc` (9E" omyyf`cubmgs mj YBJ+34 Misfyzfe UMO_R s~bg srsufk'

EMB4 3>'3?

Jblvyf sv~~`fkfgu :' 3H GKY s~fouyvk mj YBJ+3'

EMB4 3>'35

Jblvyf sv~~`fkfgu '36

Jblvyf sv~~`fkfgu 8' lOM_R s~fouyvk mj YBJ+3'

EMB4 3>'3:

Jblvyf sv~~`fkfgu 2' Fx~cgefe ejOM_R s~fouyvk mj YBJ+3'

EMB4 3>'3' Fx~cgefe ejOM_R s~fouyc mj YBJ+3'

EMB4 3>'38

Jblvyf sv~~`fkfgu 33' lHKIO s~fouyvk mj YBJ+3'

EMB4 3>'32

Jblvyf sv~~`fkfgu 39' Fx~cgefe lHKIO s~fouyvk mj YBJ+3 (H >5'>> ~~k-O 36'>86'> ~~k"'

EMB4 3>'9>

Jblvyf ?' Omgubgvfe mg gfxu ~clf
http://dx.doi.org/10.7554/eLife.00013.008http://dx.doi.org/10.7554/eLife.00013.009http://dx.doi.org/10.7554/eLife.00013.010http://dx.doi.org/10.7554/eLife.00013.011http://dx.doi.org/10.7554/eLife.00013.012http://dx.doi.org/10.7554/eLife.00013.013http://dx.doi.org/10.7554/eLife.00013.014http://dx.doi.org/10.7554/eLife.00013.015http://dx.doi.org/10.7554/eLife.00013.016http://dx.doi.org/10.7554/eLife.00013.017http://dx.doi.org/10.7554/eLife.00013.018http://dx.doi.org/10.7554/eLife.00013.019http://dx.doi.org/10.7554/eLife.00013.020http://dx.doi.org/10.7554/eLife.00013.020http://dx.doi.org/10.7554/eLife.00013.019http://dx.doi.org/10.7554/eLife.00013.018http://dx.doi.org/10.7554/eLife.00013.017http://dx.doi.org/10.7554/eLife.00013.016http://dx.doi.org/10.7554/eLife.00013.015http://dx.doi.org/10.7554/eLife.00013.014http://dx.doi.org/10.7554/eLife.00013.013http://dx.doi.org/10.7554/eLife.00013.012http://dx.doi.org/10.7554/eLife.00013.011http://dx.doi.org/10.7554/eLife.00013.010http://dx.doi.org/10.7554/eLife.00013.009http://dx.doi.org/10.7554/eLife.00013.008


8/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'>81 @ff cge Kctkcgbcg 9>3>

Cg fu c`' 9>33"' _v`jmgm`b~bes `baf YBJ+3 hczf iffg yf~myufe um hczf uhfyc~fvubo coubzbubfs, ivu uhfbfgemlfgmvs jvgoubmgs cyf gmu agm|g' _v`jmicobgs C cge I, |hboh |fyf bsm`cufe jymk uhf ovùvyf iymuhmj c Ohyrsfmicoufybvk s~' |fyf yf~myufe cs zmg \b``fiycge jcoumy yfof~umy cguclmgbsus, cge czmoybsuckbef C, jymk c yf`cufe icoufybc` s~fobfs, |cs yf~myufe cs c EGC ~m`rkfycsf bghbibumy (Ackbrckcfu c`' 3226c1 Amicrcshb fu c`' 3226"' Uhf ~fyzcsbzfgfss mj bgufycoubmgs ifu|ffg Icoufymbefufs cge

cgbkc`s (\fisufy fu c`' 9>>51\fx`fy 9>>838 (Abgl fu c`' 9>>?"' Uhf Ymsfuuf Om`mgbfsCisfgu (YOC" ovùvyf `bgf |cs ~ymevofe jymk CUOO6>838 ir sfybc` uyfcukfgu |buh oh`myck~hfgbom

(:8 l k@3

", ck~bob``bg (6> l k@3

", suyf~umkrobg (6> l k@3

", cge fyruhymkrobg (6> l k@3

(Jcbyo`mvlh fu c`' 9>3>"' C kmgmxfgbo `bgf mj_' ymsfuuc (^x3" |cs lfgfycufe ir uyfcubgl CUOO 6>838|buh c omkibgcubmg mj mmxcobg (3> l k@3", acgckrobg (6> l k@3", cge suyf~umkrobg (6> l k@3

cgubibmubos um ab`` uhf vgefgfe fgzbymgkfguc` icoufybc' Jm``m|bgl sfzfyc` ymvges mj sfybc` eb`vubmg, csbgl`f of`` |cs bsm`cufe ir JCO_ cge sv~~`fkfgufe |buh C' kcohb~mglmgfgsbs(Ecrf` fu c`' 9>33"C`` uhyff _' ymsfuuc of`` bgfs (CUOO 6>838, YOC, cge x3" |fyf lym|g bg ofyfc` lycss bgjvsfe sfc|cufcu 96O cge kcbgucbgfe ir s~`buubgl ovùvyfs 343> bgum jyfsh kfebvk fzfyr ? ecrs ( Abgl fu c`' 9>>2"@bzf of``s |fyf bkclfe |buh c @fboc EKB:>>>I kboymsom~f fvb~~fe |buh c EJO?6> JX ockfyc'

Ibmcsscr jmy ymsfuuf om`mgr efzf`m~kfguVgefy `cimycumyr omgebubmgs, _' ymsfuuc ebjjfyfgubcufs bgum c zcybfur mj of`` ur~fs bgo`vebgl cuucohfeuhfocuf of``s, sm`bucyr s|bkkfys, ymsfuuf om`mgbfs, ohcbg om`mgbfs cge mmsf, ebsmylcgbtfe cssmobcubmgsmj of``s cuucohfe um mgf cgmuhfy cu uhf om``cy my um icoufybc` ibm`ks (Ecrf` fu c`' 9>33"' _' ymsfuuc

ymsfuuf om`mgbfs ocg if ebsubglvbshfe jymk muhfy of`` ur~fs bg uhcu uhfr omgucbg o`vsufys mj cu fcsu jmvo`msf`r cssmobcufe of``s |buh mylcgbtfe ~m`cybur1 fcoh of`` mybfgufe |buh bus clf``vk ~mbgubgl mvu|cyejymk c ofguyc` jmovs' Bg uhf vc`bucubzf ibmcsscr, YOC ovùvyfs |fyf eb`vufe bg jyfsh kfebvk um c efgsburmj c~~ymxbkcuf`r 3>53>6 of``s k@3, c`bvmufe bgum 95+|f`` cu imuumk ovùvyf ebshfs (Omsucy, OmygbglGR, V_C", sv~~`fkfgufe |buh zcybmvs uyfcukfgus, cge somyfe jmy uhf ~yfsfgof my cisfgof mj ymsfuufom`mgbfs cjufy 58 hy' Jmy vcgubucubzf kfcsvyfkfgus, YOC ovùvyfs |fyf eb`vufe cs ifjmyf bgum sbx+|f`cu imuumk ovùvyf ebshfs' Um kfcsvyf uhf ~fyofguclf mj of``s |buhbg ymsfuuf om`mgbfs, fcoh |f`` |cssoyc~fe um efucoh uhfocuf of``s cge uhf umuc` gvkify mj of``s cge uhf umuc` gvkify mj of``s bg fcohymsfuuf om`mgr |fyf omvgufe |buh c Iyblhu+@bgf hfkcorumkfufy (Hcvssfy _obfgubo, Hmyshck, ^C,V_C"'

Jblvyf sv~~`fkfgu 3?' Fx~cgefe lHKIO s~fouyvk mj YBJ+3 (H >'8>3'8> ~~k-O 9>'>5>'> ~~k"'

EMB4 3>'93

Jblvyf sv~~`fkfgu 35' UMO_R s~fouyvk mj YBJ+3'

EMB4 3>'99

Jblvyf sv~~`fkfgu 36' Fx~cgefe UMO_R s~fouyvk mj YBJ+3 (H >'6>5'96 ~~k-O >'6>5'96 ~~k"'

EMB4 3>'9?

Jblvyf ?' Omgubgvfe
http://dx.doi.org/10.7554/eLife.00013.021http://dx.doi.org/10.7554/eLife.00013.022http://dx.doi.org/10.7554/eLife.00013.023http://dx.doi.org/10.7554/eLife.00013.023http://dx.doi.org/10.7554/eLife.00013.022http://dx.doi.org/10.7554/eLife.00013.021


9/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'838 |cs bsm`cufe ir sucgecye eb`vubmg~`cubgl ufohgbvf mg kmebfe Tmif`` kfebvk clc(Ocy`voob cge yckfy 326>:" yfzfc`fe suycbg ^Y3 um if kmsu o`msf`ryf`cufe um kfkifys mj uhf C`lmyb~hclvs lfgvs|buhbg uhf Icoufymbefufs ~hr`vk' ^Y3 |cs svisfvfgu`r gckfe C`lmyb~hclvs kcohb~mglmgfgsbs(Iyce`fr fu c`' 9>>2"'

Lfgfycubgl c ~hr`mlfgfubojyckf|mya jmy ufsubgl uhf ebzfysburmj icoufybc uhcu bgevof ymsfuufom`mgr efzf`m~kfgu

Um bgzfsublcuf |hfuhfy uhf cib`bur um uybllfy ymsfuufom`mgr efzf`m~kfgu |cs s~fobo um C' kcohb~mglmgfgsbs, |f ufsufe uhyff o`cssfs mj icoufybc` s~fobfs jmy uhfby kmy~hmlfgbo oc~cobur4 36 s~fobfs bguhf C`lmyb~hclvs lfgvs, 3: gmg+C`lmyb~hclv

kfkifys mj uhf Icoufymbefufs ~hr`vk, cge fblhu s~fobfs yf~yfsfgubgl uhyff ceebubmgc` kcdmy o`cefs|buhbg Icoufybc' Fcoh s~fobfs |cs soyffgfe jmy kmy~hmlfgbo coubzbur vsbgl uhf ibmcsscr jmy ymsfuufom`mgr efzf`m~kfgu' @bzf of``s jymk bgebzbevc` om`mgbfs lym|g jymk sm`be clcy ~`cufs |fyf ceefeebyfou`r um YOC ovùvyfs cge somyfe jmy uhf ~yfsfgof my cisfgof mj ymsfuuf om`mgbfs 58 hy cjufy bgmov`cubmg' Fcoh icoufybc` s~fobfs |cs ufsufe uhyff ubkfs'

Um efufykbgf uhf ~hr`mlfgfubo ebsuybivubmg mj kmy~hmlfgbo coubzbur bg uhf icoufybc` s~fobfs ufsufe(Uci`f 3", c sfvfgof c`blgkfgu mj 3:_ yEGC lfgfs jymk fcoh s~fobfs |cs lfgfycufe ir bufycubzf~cby|bsf omk~cybsmgs vsbgl J_C (Iyce`fr fu c`' 9>>2"' ^mmy`r c`blgfe yflbmgs |fyf yfkmzfe ir

Li`moas zfysbmg >'23i (Ocsuyfscgc 9>>>1 Uc`czfyc cge Ocsuyfscgc 9>>>>yf~`bocufs"'

Ibmohfkboc` cgc`rsbs mj Ymsfuuf Bgevobgl Jcoumy (YBJ+3"Um efufykbgf uhf ibmohfkboc` gcuvyf mj YBJ+3, C' kcohb~mglmgfgsbsof`` jycoubmgs cge omgebubmgfekfebvk |fyf svidfoufe um c icuufyr mj uyfcukfgus' Uhf yfsvùs mj uhfsf ufsus cyf svkkcybtfebg Uci`f 9' Omgebubmgfe kfebvk (OK" |cs lfgfycufe ir ~f``fubgl fbuhfy ohmcgmclf``cufs lym|g

Uci`f ?' Uci`f mj GKY ohfkboc` shbjus

^msbubmg 3H (kvùb~`bobur, D, /H"

3?O (,

~~k"

GH 8'93 (e, D;2'3 Ht, 3H"

3 ?'>3 (ee, D;35'9, 6'3 Ht, 3H" 63'839134f>>>3?' EMB4 3>'>5" cge ùfybgl uhfovùvyf sv~fygcucgu uhymvlh c >'99 k ~myf ùf(Kb``b~myf" um yfkmzf `bzf icoufybc' Um ufsu|hfuhfy YBJ+3 coubzbur yfvbyfe `bzf icoufybcC' kcohb~mglmgfgsbs |cs lym|g mzfygblhu cu96O, ofguybjvlfe cu 3:,>>>l jmy 3 kbg um ~f``f

of``s, cge hfcufe jmy ?> kbg cu 8>O um ab`` zbci`ficoufybc' Um ufsu |hfuhfy YBJ+3 coubzbur kblhu ifhfcu `cib`f (f'l', c ~m`r~f~ubef", C' kcohb~mglmgfgsbsOK |cs imb`fe jmy 3> kbg' Um ufsu |hfuhfYBJ+3 |cs c ~ymufbg, C' kcohb~mglmgfgsbs OK|cs bgovicufe |buh 9>> l k@3 ~ymufbgcsf A(Gf| Fgl`cge Ibm`cis, B~s|boh, KC, V_C" jmy 9 hycu ?'>3 K Î_ (omgucbgbgl 3> kK KlO`cge 3 kK OcO`9" cge bgovicufe |buh fbuhfYGcsf C (3>> l k@31 _blkc" my EGcsf B (3>> lk@31 _blkc" jmy 9'6 hy cu ? kK UybsO` ivjjfy (~H 8'>", omgucbgbgl 9& smebvkemefor` sv`jcuf (_E_", 5& 9+kfyoc~umfuhcgm`, cge 9 kK KlO`9' Uhf kbxuvyf |cs zmyufxfe cge bgovicufe cu :6O vgub` sm`vib`btfe' ymufbgcsf A (9> kl k@3" |cs ceefe um uhf kbxuvyf, cge bgovicufe c:6O jmy cg ceebubmgc` hmvy, jm``m|fe ir ?O um c``m| ~yfob~bucuf um jmyk' Uhf kbxuvyf |cs ofguybjvlfe c5>>>l jmy 36 kbg, cge uhf sv~fygcucgu ebsocyefe' Uhf ~yfob~bucuf |cs svs~fgefe bg ebsub``fe |cufy

? K smebvk cofucuf |cs ceefe, cge uhf kbxuvyf zmyufxfe' Jm``m|bgl ceebubmg mj omè cism`vuf fuhcgm`, uhf kbxuvyf |cs zmyufxfe clcbg, cge uhf svs~fgsbmg clcbg c``m|fe um ~yfob~bucuf mzfygblhu c9>O' Cjufy uhf ofguybjvlcubmg, uhf ~yfob~bucuf |cs svs~fgefe bg 3> kK UybsO` (~H >>l jmy 36 kbg' Uhf um~ cvfmvs crfy |cs yfkmzfe, cge uhf ~hfgm`bo crfy yf+fxuycoufe|buh cg fvc` zm`vkf mj ebsub``fe |cufy' Uhbs sck~`f |cs clcbg bgovicufe cu :6O jmy 36 kbg cge uhfg~`cofe bg bof |cufy' Cjufy ofguybjvlcubmg cu :>>>l jmy 36 kbg, uhf u|m cvfmvs crfys |fyf omkibgfecge ebc`rtfe clcbgsu kvùb~`f ohcglfs mj ebsub``fe |cufy mzfy 9 ecrs'

Jblvyf 5' ^vybfe YBJ+3 bs coubzf cu ~`cvsbi`f fgzbymg+

kfguc` omgofguycubmgs' YBJ+3 omgofguycubmgs ycglbgl

jymk 3>9 um 3>< jK bgevof ymsfuuf om`mgr efzf`m~kfgu

bg YOC ovùvyfs' Jyfvfgor mj ymsfuuf om`mgr efzf`m~+

kfgu |cs vcgubfe bg YOC ovùvyfs 9 ecrs cjufy

uyfcukfgu |buh c eb`vubmg sfybfs mj ~vybfe YBJ+3' Ecuc

cyf kfcg s'f' jymk uhyff bgef~fgefgu fx~fybkfgus'

@bgf bgebocufs gmg+`bgfcy yflyfssbmg mj uhf YBJ+3 coubzbur

~ym`f'

EMB4 3>'96

Uhf jm``m|bgl lvyf sv~~`fkfgus cyf czcb`ci`f jmy

lvyf 54

Jblvyf sv~~`fkfgu 3' Efufoubmg mj ~vybfe YBJ+3'

EMB4 3>'9:

Jblvyf sv~~`fkfgu 9' Efufoubmg mj YBJ+3 bg uhf

omgebubmgfe kfebvk mjC' kcohb~mglmgfgb'

EMB4 3>'9'98
http://dx.doi.org/10.7554/eLife.00013.025http://dx.doi.org/10.7554/eLife.00013.026http://dx.doi.org/10.7554/eLife.00013.027http://dx.doi.org/10.7554/eLife.00013.028http://dx.doi.org/10.7554/eLife.00013.028http://dx.doi.org/10.7554/eLife.00013.027http://dx.doi.org/10.7554/eLife.00013.026http://dx.doi.org/10.7554/eLife.00013.025


11/16

Of`` ibm`mlr

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uhf cyubo`f


13/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'>9' _c`bgbicoufy yvify lfg' gmz',

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14/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'3>' Kv`ubof``v`cy efzf`m~kfgu bg c ohmcgmclf``cuf' Ovyy Ibm`9>4 Y8' Oc~gmorum~hclc s~~' omgucbg sv`jmgm`b~bes uhcu cyf gmzf` bg ~ymocyrmufs'D Icoufybm`3554 629:>9'

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Hbiifye ED' 32


15/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>':'Kcusvgclc U, Mackvyc R, Jvavec R, \chrveb CU, Kvycsf R, Ucafrckc H' 9>>6' Omk~`fuf lfgmkf sfvfgof mj

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icoufybvk' _obfgof?>>6' Cg bkkvgmkmev`cumyr km`fov`f mj srkibmubo icoufybc

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16/16

Of`` ibm`mlr

C`flcem fu c`' f@bjf 9>39134f>>>3?' EMB4 3>'