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Iko kushanduka kwehutachiona hwehutachiona hunosanganisira kupokana pakati pekusarudzwa kwechisikigo, izvo zvinoita kuti zvipembenene zvigadzirike, uye genetic drift, izvo zvinoita kuti zvipembenene zvirasikirwe nemajini uye kuunganidza zvinokanganisa kuchinja.Pano, kuti tinzwisise kuti kupokana uku kunoitika sei pachiyero chemacromolecule imwe chete, tinotsanangura chimiro che cryo-EM cheribosome yeEncephalitozoon cuniculi, chisikwa cheeukaryotic chine rimwe rema genomes madiki pane zvakasikwa.Kunyanya kudzikiswa kweRRNA muE. cuniculi ribosomes kunoperekedzwa neshanduko yezvimiro zvisati zvamboitika, sekushanduka kweiyo yaimbozivikanwa yakasanganiswa rRNA linkers uye rRNA isina mabulges.Mukuwedzera, iyo E. cuniculi ribosome yakapona kurasikirwa kweRRNA zvimedu uye mapuroteni kuburikidza nekuvandudza kukwanisa kushandisa mamorekuru madiki semisiki yemaitiro ezvakaora rRNA zvimedu uye mapuroteni.Pakazara, isu tinoratidza kuti zvimiro zvemamorekuru zvakafunga kwenguva refu kuderedzwa, kuderera, uye zvichienderana nekuchinja kunokonzeresa kune huwandu hwekugadzirisa nzira dzinoita kuti dzirambe dzichishanda kunyangwe zvakanyanyisa kunyura kwemamorekuru.
Nekuti mapoka mazhinji ezvipembenene zvipembenene zvine maturusi emushonga akasarudzika ekushandisa mauto avo, isu kazhinji tinofanirwa kugadzira nzira dzakasiyana dzekurapa dzemapoka akasiyana ezvipembenene1,2.Zvisinei, humbowo hutsva hunoratidza kuti zvimwe zvinhu zvekushanduka-shanduka kweparasite zvinoshanduka uye zvinonyanya kufanotaurwa, zvichiratidza hwaro hunogona kuitika hwekupindira kwekurapa kwakakura muhutachiona hwehutachiona3,4,5,6,7,8,9.
Basa rakapfuura rakaratidza maitiro ekushanduka-shanduka muhutachiona hwehutachiona hunonzi genome reduction kana genome decay10,11,12,13.Tsvagiridzo yazvino inoratidza kuti kana ma microorganisms akasiya mararamiro emahara uye ave intracellular parasites (kana endosymbionts), genomes avo anononoka asi anoshamisa metamorphoses pamusoro pemamiriyoni emakore9,11.Mukuita kunozivikanwa sekuora kwegenome, zvipembenene zvidiki zvinounganidza zvinodzima zvinoshandura majini akawanda aimbokosha kuita mapseudogenes, zvichiita kuti zvishoma nezvishoma kurasikirwa kwemajini uye kuparara kwekuchinja14,15.Kuputsika uku kunogona kuparadza kusvika ku95% yemajini muzvisikwa zvekare zvemukati zvemukati zvichienzaniswa nemhando dzakasununguka dzinorarama.Nokudaro, kushanduka kwema-intracellular parasites ndeyekukwevera-hondo pakati pemasimba maviri anopikisana: Darwinan natural selection, zvichiita kuti pave nekuvandudzwa kwezvipembenene, uye kuparara kwejenome, kukanda zvipembenene mukukanganwa.Kuti utachiona hwakakwanisa sei kubuda kubva mukudhonzana uku uye nekuchengeta chiitiko chechimiro chayo chemolecular hazvisati zvajeka.
Kunyangwe iyo nzira yekuora kwegenome isinganzwisisike zvizere, inoratidzika kunge ichiitika zvakanyanya nekuda kweiyo genetic kudonha.Nekuti maparasite anogara mudiki, asexual, uye genetically mashoma ehuwandu, haakwanise kubvisa zvinokonzeresa shanduko dzinoitika dzimwe nguva panguva yekudzokororwa kweDNA.Izvi zvinotungamira mukuunganidzwa kusingadzoreki kwekuchinja kunokuvadza uye kuderedzwa kweparasite genome.Nekuda kweizvozvo, parasite haingorasikirwe majini ayo asingachakoshi kuti ararame munzvimbo ye intracellular.Iko kusakwanisa kwehuwandu hwemaparasite kubvisa zvinobudirira kuchinja kwakashata kunokonzeresa kuti shanduko idzi dziunganidze mukati mejenome, kusanganisira iwo akakosha majini.
Zvakawanda zvemanzwisisiro edu emazuva ano ekudzikisa genome anobva chete pakuenzaniswa kwemajenome sequences, nekutarisisa kushoma kune shanduko mumamorekuru chaiwo anoita mabasa ekuchengetedza imba uye anoshanda seanogona zvinodhaka zvinodhaka.Ongororo dzekuenzanisa dzakaratidza kuti mutoro wekubvisa intracellular microbial mutations inoita senge inofanotungamira mapuroteni uye nucleic acids kusapeta uye kuunganidza, zvichiita kuti vawedzere kutsamira uye hypersensitive kune heat19,20,21,22,23.Pamusoro pezvo, zvipembenene zvakasiyana-siyana-kushanduka-shanduka kwakazvimiririra dzimwe nguva zvakaparadzaniswa nemakore anosvika 2.5 bhiriyoni-zvakaona kurasikirwa kwakafanana kwenzvimbo dzekutonga kwemhando mumaprotein synthesis5,6 uye nzira dzekugadzirisa DNA24.Nekudaro, zvishoma zvinozivikanwa nezve mabatiro emararamiro e intracellular pane zvimwe zvese zvema cellular macromolecules, kusanganisira kuchinjika kwema molecular kumutoro unowedzera wekudzima shanduko.
Mubasa iri, kuitira kuti tinzwisise zviri nani kushanduka kwemapuroteni uye nucleic acids ye intracellular microorganisms, takasarudza chimiro cheribosomes ye intracellular parasite Encephalitozoon cuniculi.E. cuniculi imhuka yakaita sefungus yeboka reparasitic microsporidia ine madiki eukaryotic genomes uye saka anoshandiswa semuenzaniso wezvipenyu kudzidza kuora kwegenome25,26,27,28,29,30.Munguva pfupi yapfuura, cryo-EM ribosome chimiro chakatemerwa kuderedzwa zvine mwero genomes eMicrosporidia, Paranosema locustae, uye Vairimorpha necatrix31,32 (~ 3.2 Mb genome).Zvimiro izvi zvinoratidza kuti kumwe kurasikirwa kweRRNA kukwidziridzwa kunobhadharwa nekuvandudzwa kwekutsva kwekusangana pakati pevakidzani mapuroteni eribosomal kana kutorwa kwetsva msL131,32 ribosomal proteins.Zvisikwa Encephalitozoon (genome ~ 2.5 miriyoni bp), pamwe chete nehama yavo yepedyo Ordospora, vanoratidza dhigirii rekupedzisira rekuderedzwa kwegenome mueukaryotes - vane asingasviki 2000 mapuroteni-coding majini, uye zvinotarisirwa kuti ribosomes avo haana chete rRNA ekuwedzera zvimedu mapuroteni eribosomal nekuda kwekushaikwa kwehomologues muE. cuniculi genome26,27,28.Nokudaro, takagumisa kuti E. cuniculi ribosome inogona kuratidza nzira dzaimbova dzisingazivikanwi dzekugadzirisa ma molecular kuparara kwegenome.
Yedu cryo-EM chimiro chinomiririra diki eukaryotic cytoplasmic ribosome kuti ionekwe uye inopa nzwisiso yekuti iyo yekupedzisira dhigirii yekudzikisira genome inokanganisa sei chimiro, kuungana, uye kushanduka kwemuchina wemamorekuru akabatana nesero.Takaona kuti E. cuniculi ribosome inotyora mitemo yakawanda yakachengetedzwa yeRNA kupetwa uye ribosome kusangana, uye takawana itsva, yaimbozivikanwa ribosomal protein.Zvisingatarisirwi, tinoratidza kuti microsporidia ribosomes yakashandura kugona kusunga mamorekuru madiki, uye kufungidzira kuti kuderedzwa muRRNA nemapuroteni kunokonzeresa hunyanzvi hwekushanduka-shanduka hunogona kuzopa hunhu hunobatsira pane ribosome.
Kuti tivandudze manzwisisiro edu ekushanduka kweprotein uye nucleic acids mu intracellular organisms, takasarudza kuparadzanisa E. cuniculi spores kubva kune tsika dzemasero ane utachiona hwemammalian kuitira kuchenesa ribosomes yavo uye kuona maitiro eiri ribosomes.Zvakaoma kuwana nhamba huru yeparasitic microsporidia nokuti microsporidia haigoni kugadzirwa mune zvinovaka muviri.Pane kudaro, dzinokura uye dzinoberekana chete mukati mesero rinogamuchira.Naizvozvo, kuti tiwane E. cuniculi biomass yekuchenesa ribosome, takatapurira mammalian itsvo cell line RK13 neE. cuniculi spores uye takagadzira maseru ane utachiona aya kwemavhiki akati wandei kuti E. cuniculi ikure nekuwanda.Tichishandisa cell cell monolayer ine utachiona inosvika hafu yemaskweya mita, takakwanisa kuchenesa inenge 300 mg yeMicrosporidia spores uye kuishandisa kuparadzanisa ribosomes.Takazovhiringidza spores dzakacheneswa negirazi beads uye tichibva tabvisa crude ribosomes tichishandisa stepwise polyethylene glycol fractionation yemalysates.Izvi zvakatibvumira kuwana ingangoita 300 µg yeE. cuniculi ribosomes mbishi yekuongorora maitiro.
Takazotora mifananidzo ye-cryo-EM tichishandisa masampuli e-ribosome akazoita uye takagadzirisa mifananidzo iyi tichishandisa masiki anoenderana nehombe ribosomal subunit, diki subunit musoro, uye diki subunit.Munguva iyi, takaunganidza mifananidzo ye108,000 ribosomal particles uye computed cryo-EM mifananidzo ine chisarudzo che 2.7 Å (Supplementary Figures 1-3).Takabva tashandisa cryoEM mifananidzo kuenzanisa rRNA, ribosomal protein, uye hibernation factor Mdf1 yakabatana neE. cuniculi ribosomes (Fig. 1a, b).
a Structure of the E. cuniculi ribosome in complex with hibernation factor Mdf1 (pdb id 7QEP).b Mepu yehibernation factor Mdf1 yakabatana neE. cuniculi ribosome.c Sekondari chimiro mepu ichienzanisa yakadzoserwa rRNA muMicrosporidian marudzi kune anozivikanwa ribosomal zvimiro.Iwo mapaneru anoratidza nzvimbo yeakakwidziridzwa rRNA zvimedu (ES) uye ribosome inoshanda nzvimbo, kusanganisira iyo decoding saiti (DC), sarcinicin loop (SRL), uye peptidyl transferase centre (PTC).d The electron density inoenderana nepeptidyl transferase centre yeE. cuniculi ribosome inoratidza kuti iyi catalytic site ine chimiro chakafanana muE. cuniculi parasite uye mauto ayo, kusanganisira H. sapiens.e, f Kuwanda kwemaerekitironi kunoenderana nepakati pekudhikodha (e) uye chimiro chechirongwa chenzvimbo yekutsikisa (f) inoratidza kuti E. cuniculi ine zvisaririra U1491 pachinzvimbo cheA1491 (E. coli manhamba) mune mamwe akawanda eukaryotes.Shanduko iyi inoratidza kuti E. cuniculi inogona kuva nehanya nemishonga inorwisa mabhakitiriya inonangana nenzvimbo ino inoshanda.
Kusiyana neyakagadzikwa zvimiro zveV. necatrix uye P. locustae ribosomes (zvose zviri zviviri zvinomiririra imwechete microsporidia mhuri yeNosematidae uye yakafanana zvakanyanya kune imwe neimwe), 31,32 E. cuniculi ribosomes inopinda maitiro akawanda eRRNA uye mapuroteni kupatsanurwa.Kuwedzera denaturation (Supplementary Figures 4-6).MuRRNA, shanduko dzakanyanya kushamisa dzaisanganisira kurasikirwa kwakakwana kweiyo amplified 25S rRNA fragment ES12L uye kupera kwechikamu cheh39, h41, uye H18 helices (Fig. 1c, Supplementary Fig. 4).Pakati pemapuroteni eribosomal, shanduko dzinonyanya kushamisa dzaisanganisira kurasikirwa kwakakwana kweprotein yeS30 uye kupfupika kweEL8, eL13, eL18, eL22, eL29, eL40, uS3, uS9, uS14, uS17, uye eS7 mapuroteni (Supplementary Figures 4, 5).
Nokudaro, kuderera kwakanyanya kwemajenomes eEncephalotozoon/Ordospora marudzi kunoratidzwa muchimiro chavo cheribosome: E. cuniculi ribosomes inosangana nekurasikirwa kunoshamisa kweprotein content mu eukaryotic cytoplasmic ribosomes zvichienderana nekuumbwa kwemaitiro, uye havana kunyange iyo rRNA uye mapuroteni ezvimedu zvemaprotein ehupenyu hutatu chete, asi mapeji matatu akazara ehupenyu husina kusimba.Chimiro cheE. cuniculi ribosome chinopa yekutanga molecular model yekuchinja uku uye inoratidza zviitiko zvekushanduka-shanduka zvakave zvisingatarisirwi nezvose zviri zviviri kuenzanisa genomics uye zvidzidzo zve intracellular biomolecular structure (Supplementary Fig. 7).Pazasi, tinotsanangura chimwe nechimwe chezviitiko izvi pamwe chete nemabviro azvo ekushanduka-shanduka uye kugona kwavo kuita ribosome basa.
Takazoona kuti, mukuwedzera kune rRNA truncations yakakura, E. cuniculi ribosomes ine rRNA mutsauko pane imwe nzvimbo yavo inoshanda.Kunyange zvazvo peptidyl transferase centre yeE. cuniculi ribosome ine chimiro chakafanana nemamwe eukaryotic ribosomes (Fig. 1d), nzvimbo yedecoding inosiyana nekuda kwekusiyana kwekutevedzana pa nucleotide 1491 (E. coli nhamba, Fig. 1e, f).Kucherekedza uku kwakakosha nekuti saiti yekutsikisa eukaryotic ribosomes inowanzove ine zvisaririra G1408 neA1491 zvichienzaniswa nemhando yebhakitiriya A1408 uye G1491.Musiyano uyu unotsigira kunzwisiswa kwakasiyana kwebhakitiriya uye eukaryotic ribosomes kumhuri yeaminoglycoside yeribosomal antibiotics uye mamwe mamorekuru madiki anonangana nenzvimbo yekudhirodha.Panzvimbo yekudhirodha yeE. cuniculi ribosome, zvakasara zveA1491 zvakatsiviwa neU1491, zvichigona kugadzira chimiro chakasiyana chekusunga mamorekuru madiki akanangana nenzvimbo ino inoshanda.Iyo yakafanana A14901 musiyano uripowo mune dzimwe microsporidia dzakadai seP. locustae uye V. necatrix, zvichiratidza kuti yakapararira pakati pe microsporidia marudzi (Fig. 1f).
Nekuti E. cuniculi ribosome samples yedu yakaparadzaniswa kubva kune metabolically inactive spores, takaedza cryo-EM mepu yeE. cuniculi yeyakambotsanangurwa ribosome kusunga pasi pekunetseka kana nzara.Hibernation factors 31,32,36,37, 38. Takafananidza chimiro chakambogadzwa chehibernating ribosome ne cryo-EM mepu yeE. cuniculi ribosome.Nokuda kwekuvhara, S. cerevisiae ribosomes yakashandiswa mumatambudziko ane hibernation factor Stm138, ribosomes yemhashu mumatambudziko ane Lso232 factor, uye V. necatrix ribosomes yakaoma neMdf1 uye Mdf231 zvinhu.Panguva imwecheteyo, takawana iyo cryo-EM density inoenderana neyakasara factor Mdf1.Zvakafanana neMdf1 inosunga kuV. necatrix ribosome, Mdf1 inosungirawo kuE. cuniculi ribosome, iyo inovhara nzvimbo yeE ye ribosome, zvichida kubatsira kuita kuti ribosomes ivepo apo parasite spores inenge isingaiti metabolically inactivation (Mufananidzo 2).)
Mdf1 inovharira E saiti ye ribosome, inoita seino batsira kumisa ribosome apo parasite spores paita metabolically isingaite.Muchigadziro cheE. cuniculi ribosome, takaona kuti Mdf1 inoumba kusangana kwaimbozivikanwa neL1 ribosome stem, chikamu cheribosome chinobatsira kusunungurwa kwe deacylated tRNA kubva mu ribosome panguva yeprotein synthesis.Aya maitirwo anoratidza kuti Mdf1 inoparadzanisa kubva ku ribosome ichishandisa nzira imwechete se deacetylated tRNA, ichipa tsananguro inogoneka yekuti ribosome inobvisa sei Mdf1 kuti iitezve mapuroteni synthesis.
Nekudaro, chimiro chedu chakaratidza kusangana kusingazivikanwe pakati peMdf1 neL1 ribosome gumbo (chikamu cheribosome chinobatsira kuburitsa deacylated tRNA kubva muribosome panguva yeprotein synthesis).Kunyanya, Mdf1 inoshandisa zvibatanidzi zvakafanana sechikamu chegokora che deacylated tRNA molecule (Fig. 2).Iyi yaimbove isingazivikanwe molecular modelling yakaratidza kuti Mdf1 inozviparadzanisa kubva ku ribosome ichishandisa nzira imwechete sedeacetylated tRNA, iyo inotsanangura kuti ribosome inobvisa sei iyi hibernation factor kuti iitezve protein synthesis.
Pakugadzira rRNA modhi, takaona kuti E. cuniculi ribosome ine abnormally akapeta rRNA zvidimbu, izvo takadana fused rRNA (Fig. 3).Mune ribosomes inotenderera madomasi matatu ehupenyu, rRNA inopeta kuita zvimiro umo mabhesi mazhinji eRRNA angave mabhesi maviri uye anopeta pamwe chete kana kupindirana nemapuroteni eribosomal38,39,40.Zvisineyi, muE. cuniculi ribosomes, rRNAs inoratidzika kunge inotyora mutemo wekupeta iyi nekushandura mamwe ehelices awo kuita matunhu eRNA asina kuvhurika.
Chimiro cheH18 25S rRNA helix muS. cerevisiae, V. necatrix, uye E. cuniculi.Kazhinji, muma ribosomes anotora matunhu matatu ehupenyu, chinongedzo ichi chinopinda muRNA helix ine 24 kusvika 34 zvisaririra.MuMicrosporidia, zvakasiyana, iyi rRNA linker inoderedzwa zvishoma nezvishoma kusvika kune maviri-stranded uridine-rich linkers ane masara gumi nemaviri chete.Zvizhinji zvezvisaririra izvi zvinosangana nezvinonyungudutsa.Nhamba yacho inoratidza kuti parasitic microsporidia inoita seinotyora misimboti yeRRNA kupeta, uko mabhesi eRRNA anowanzo kubatanidzwa kune mamwe mabhesi kana kubatanidzwa muRRNA-protein kudyidzana.Mu microsporidia, zvimwe zvidimbu zveRRNA zvinotora kupeta kusingafadzi, umo iyo yekare rRNA helix inova chidimbu chine tambo chakareba chakareba mumutsara wakatwasuka.Kuvepo kweaya matunhu asina kujairika kunobvumira microsporidia rRNA kusunga kure kure rRNA zvimedu uchishandisa shoma nhamba yemabhesi eRNA.
Muenzaniso unoshamisa weiyi shanduko yekushanduka-shanduka inogona kuonekwa muH18 25S rRNA helix (Fig. 3).Muzvipenyu kubva kuE. coli kusvika kuvanhu, mabhesi eiyi rRNA helix ane 24-32 nucleotides, ichiita helix isina kukwana zvishoma.Mune zvakambozivikanwa ribosomal structures kubva kuV. necatrix uye P. locustae,31,32 mabhesi eH18 helix haana kuvharwa zvishoma, asi nucleotide base pairing inochengetedzwa.Zvakadaro, muE. cuniculi ichi rRNA chimedu chinova chinongedzo chipfupi 228UUUGU232 uye 301UUUUUUUU307.Kusiyana neyakajairwa rRNA zvimedu, izvi uridine-rich linkers hazvibatike kana kubata zvakanyanya ne ribosomal mapuroteni.Pane kudaro, vanotora zvigadziriso-zvakavhurika uye zvizere zvimisikidzo umo rRNA tambo dzakatambanudzwa dzinenge dzakati twasa.Iyi conformation yakatambanudzwa inotsanangura mashandisiro anoita E. cuniculi mabhesi gumi nemaviri eRNA chete kuzadza 33 Å gap pakati peH16 neH18 rRNA helices, nepo mamwe marudzi anoda kanenge kaviri kaviri rRNA mabhesi ekuzadza gap.
Nekudaro, isu tinogona kuratidza kuti, kuburikidza nekupeta zvine simba kusingafadzi, parasitic microsporidia yakagadzira nzira yekubvumirana kunyange izvo zvikamu zveRRNA zvinoramba zvakachengetedzwa mukati mezvipenyu muzvikamu zvitatu zvehupenyu.Sezviri pachena, kuburikidza nekuunganidza shanduko dzinoshandura rRNA helices kuita mapfupi epoly-U linkers, E. cuniculi inogona kuumba zvisingawanzo rRNA zvimedu zvine manucleotides mashoma sezvinobvira pakubatanidza zvidimbu zve distal rRNA.Izvi zvinobatsira kutsanangura kuti microsporidia yakawana sei kudzikiswa kunoshamisa mune yavo yekutanga mamorekuru chimiro pasina kurasikirwa kwavo kwechimiro uye kushanda kwekuvimbika.
Chimwe chinhu chisina kujairika cheE. cuniculi rRNA chitarisiko cheRRNA pasina thickenings (Fig. 4).Mabulge ari nucleotides asina ma base pairs anomonyoroka kubva muRNA helix pane kuvanda mairi.Mazhinji rRNA protrusions anoita semamolecular adhesives, achibatsira kusunga ari pedo neribosomal mapuroteni kana zvimwe rRNA zvimedu.Mamwe mabhururu anoita sehinges, achibvumira rRNA helix kuti ishanduke uye kupeta zvakakwana kune chibereko cheprotein synthesis 41.
a An rRNA protrusion (S. cerevisiae numbering) haipo paE. cuniculi ribosome structure, asi iripo mune mamwe akawanda eukaryotes b E. coli, S. cerevisiae, H. sapiens, uye E. cuniculi internal ribosomes.maparasite haana akawanda ekare, akachengetedzwa zvakanyanya rRNA bulges.Aya makobvu anodzikamisa iyo ribosome chimiro;saka, kusavapo kwavo mu microsporidia kunoratidza kuderera kwakadzikama kweRRNA kupeta mu microsporidia parasites.Kuenzanisa neP stems (L7 / L12 inodonhedzwa mumabhakitiriya) inoratidza kuti kurasikirwa kweRRNA zviputi dzimwe nguva kunopindirana nekuonekwa kwemapundu matsva pedyo nemapundu akarasika.Iyo H42 helix mu23S/28S rRNA ine bulge yekare (U1206 muSaccharomyces cerevisiae) inofungidzirwa kuti ingangoita 3.5 bhiriyoni yemakore nekuda kwekuchengetedzwa kwayo munzvimbo nhatu dzehupenyu.Mu microsporidia, bulge iyi inobviswa.Zvisinei, bhururu idzva rakaonekwa pedyo nerakarasika (A1306 muE. cuniculi).
Zvinoshamisa, takaona kuti E. cuniculi ribosomes inoshaya yakawanda yeRRNA bulges inowanikwa mune mamwe marudzi, kusanganisira anopfuura 30 bulges akachengetwa mune mamwe eukaryotes (Fig. 4a).Kurasikirwa uku kunobvisa vakawanda vanosangana pakati ribosomal subunits uye pedyo rRNA helices, dzimwe nguva kugadzira hombe mhango voids mukati ribosome, zvichiita E. cuniculi ribosome zvikuru porous kana zvichienzaniswa zvakawanda chinyakare ribosomes (Fig. 4b).Zvinonyanya kukosha, takaona kuti dzakawanda zvezviputi izvi zvakarasikawo mune zvakambozivikanwa V. necatrix uye P. locustae ribosome zvivako, izvo zvakaregeredzwa nekuongorora kwekare kwemaitiro31,32.
Dzimwe nguva kurasikirwa kweRRNA kuputika kunoperekedzwa nekuvandudzwa kwezvitsva zvitsva pedyo nekuparara kwakarasika.Semuenzaniso, ribosomal P-stem ine U1208 bulge (mu Saccharomyces cerevisiae) iyo yakapona kubva kuE. coli kusvika kuvanhu uye naizvozvo inofungidzirwa kuva nemakore 3.5 bhiriyoni.Munguva yeprotein synthesis, iyi bulge inobatsira iyo P hunde kufamba pakati peyakavhurika uye yakavharika conformations kuitira kuti ribosome itore zvinhu zvekushandura uye kuendesa kune inoshanda saiti.MuE. cuniculi ribosomes, kukora uku hakuna;zvisinei, hutsva hutsva (G883) hunowanikwa chete mumatatu matatu ekutanga hunogona kubatsira pakudzorerwa kwehutano hwakanaka hweP stem (Fig. 4c).
Yedu data paRRNA isina mabulges inoratidza kuti rRNA kuderedzwa hakugumiri pakurasikirwa kwezvinhu zveRRNA pamusoro peiyo ribosome, asi inogonawo kusanganisira iyo ribosome nucleus, kugadzira parasite-chaiyo molecular defect iyo isina kutsanangurwa mumaseru akasununguka.zvisikwa zvipenyu zvinoonekwa.
Mushure mekuenzanisa canonical ribosomal mapuroteni uye rRNA, takaona kuti zvakajairwa ribosomal zvikamu hazvigone kutsanangura zvikamu zvitatu zveiyo cryo-EM mufananidzo.Zviviri zvezvimedu izvi zvidiki mamorekuru muhukuru (Fig. 5, Supplementary Fig. 8).Chikamu chekutanga chinoputirwa pakati peRibosomal proteins uL15 uye eL18 munzvimbo inowanzogarwa neC-terminus yeL18, iyo inopfupiswa muE. cuniculi.Kunyangwe isu tisingakwanise kuziva kuzivikanwa kwemorekuru uyu, ukuru uye chimiro cheichi density chitsuwa chinotsanangurwa zvakanaka nekuvapo kwespermidine mamorekuru.Kusungirirwa kwayo kune ribosome kunogadziriswa ne microsporidia-specific mutations mumaprotein eL15 (Asp51 neArg56), anoita seanowedzera hukama hweribosome yeiyi molecule diki, sezvo ivo vachibvumira uL15 kuputira molecule diki kuita ribosomal chimiro.Supplementary Figure 2).8, data yekuwedzera 1, 2).
Cryo-EM imaging inoratidza kuvepo kwemanucleotides kunze kweribose yakasungwa kuE. cuniculi ribosome.MuE. cuniculi ribosome, nucleotide iyi inogara panzvimbo imwechete ne25S rRNA A3186 nucleotide (Saccharomyces cerevisiae numbering) mune mamwe akawanda eukaryotic ribosomes.b Muchimiro cheribosomal cheE. cuniculi, nucleotide iyi inowanikwa pakati pemapuroteni eribosomal uL9 neL20, nokudaro kudzikamisa kusangana pakati pemapuroteni maviri.cd eL20 sequence kuchengetedza kuongororwa pakati pe microsporidia marudzi.Muti we phylogenetic weMicrosporidia marudzi (c) uye kutevedzana kwakawanda kweL20 protein (d) inoratidza kuti nucleotide-binding residues F170 neK172 inochengetedzwa muMicrosporidia yakawanda, kunze kweS.e Iyi nhamba inoratidza kuti nucleotide-binding residues F170 neK172 iripo chete mu eL20 ye microsporidia genome yakaderedzwa zvikuru, asi kwete mune mamwe eukaryotes.Pakazere, idzi data dzinoratidza kuti Microsporidian ribosomes yakagadzira nucleotide inosunga saiti inoita seinosunga AMP mamorekuru uye inoashandisa kudzikamisa mapuroteni-protein kudyidzana mune ribosomal chimiro.Kuchengetedzwa kwepamusoro kweiyi saiti inosunga muMicrosporidia uye kusavapo kwayo mune mamwe eukaryotes kunoratidza kuti saiti iyi inogona kupa sarudzo yekupona yeMicrosporidia.Nokudaro, iyo nucleotide-binding pocket mu microsporidia ribosome hairatidzike sechinhu chakaora kana chimiro chekupedzisira cheRRNA degradation sezvakatsanangurwa kare, asi pane inobatsira shanduko yekuvandudza inobvumira microsporidia ribosome kusunga zvakananga mamorekuru maduku, achiashandisa sezvivharo zvekuvaka mamorekuru.zvidhinha zvekuvaka ribosomes.Kuwanikwa uku kunoita kuti microsporidia ribosome ive yega ribosome inozivikanwa kushandisa nucleotide imwechete sechivakwa chayo chekuvaka.f Hypothetical evolutionary nzira inotorwa kubva nucleotide kusunga.
Yechipiri yakaderera molecular uremu density inowanikwa pane iyo interface pakati pe ribosomal mapuroteni uL9 uye eL30 (Fig. 5a).Iyi interface yakambotsanangurwa muchimiro cheSaccharomyces cerevisiae ribosome senzvimbo inosunga ye25S nucleotide yerRNA A3186 (chikamu che ES39L rRNA extension)38.Yakaratidzwa kuti mukuderera kweP. locustae ES39L ribosomes, iyi interface inosunga imwe isingazivikanwe nucleotide 31, uye inofungidzirwa kuti iyi nucleotide yakaderedzwa yekupedzisira fomu yeRRNA, umo kureba kweRRNA i ~ 130-230 mabhesi.ES39L yakaderedzwa kuita imwechete nucleotide 32.43.Yedu cryo-EM mifananidzo inotsigira pfungwa yekuti density inogona kutsanangurwa nema nucleotides.Zvisinei, kugadziriswa kwepamusoro kwechimiro chedu kwakaratidza kuti nucleotide iyi inonzi extraribosomal molecule, zvichida AMP (Fig. 5a, b).
Takazobvunza kuti nzvimbo inosunga nucleotide yakaonekwa muE. cuniculi ribosome here kana kuti yaivepo kare.Sezvo nucleotide inosunga ichinyanya kupindirana nePhe170 neLys172 zvakasara muL30 ribosomal protein, takaongorora kuchengetedzwa kwezvisaririra izvi mu4396 inomiririra eukaryotes.Sezvakaitika muL15 pamusoro, takaona kuti Phe170 neLys172 zvakasara zvakachengetwa zvakanyanya chete muMicrosporidia, asi zvisipo mune dzimwe eukaryotes, kusanganisira atypical Microsporidia Mitosporidium uye Amphiamblys, umo ES39L rRNA fragment haina kuderedzwa-e).
Zvakatorwa pamwe chete, idzi data dzinotsigira pfungwa yokuti E. cuniculi uye zvichida mamwe canonical microsporidia akashandura kukwanisa kubata nematabolites maduku muhutano hwe ribosome kubhadhara kuderera kwe rRNA uye mapuroteni.Mukuita izvi, vakagadzira kugona kwakasiyana kwekusunga nucleotides kunze kweribosome, zvichiratidza kuti parasitic molecular structures inobhadhara nekutora akawanda madiki metabolites uye nekuashandisa semisiki yekumisikidza yeRNA yakaora uye mapuroteni zvimedu..
Chikamu chechitatu chisina kufananidzwa chemepu yedu ye-cryo-EM, inowanikwa mune yakakura ribosomal subunit.Kugadziriswa kwepamusoro (2.6 Å) kwemepu yedu kunoratidza kuti density iyi ndeyemapuroteni ane akasiyana masanganiswa emacheni mahombe epadivi, izvo zvakatitendera kuziva density iyi seyaimbozivikanwa ribosomal protein yatakaziva kuti Yakanzi msL2 (Microsporidia- specific protein L2) (maitiro, mufananidzo 6).Kutsvaga kwedu homology kwakaratidza kuti msL2 inochengeterwa muMicrosporidia clade yerudzi Encephaliter uye Orosporidium, asi isipo mune mamwe marudzi, kusanganisira mamwe Microsporidia.Mune ribosomal chimiro, msL2 inotora gap rinoumbwa nekurasikirwa kweiyo yakawedzera ES31L rRNA.Muchisina ichi, msL2 inobatsira kudzikamisa rRNA kupeta uye inogona kubhadhara kurasikirwa kweES31L (Mufananidzo 6).
a Electron density and model of the Microsporidia-specific ribosomal protein msL2 inowanikwa muE. cuniculi ribosomes.b Mazhinji eukaryotic ribosomes, kusanganisira 80S ribosome yeSaccharomyces cerevisiae, ane ES19L rRNA amplification yakarasika muMicrosporidian dzakawanda.Chimiro chekare cheV. necatrix microsporidia ribosome chinoratidza kuti kurasikirwa kweES19L mumaparasite aya kunobhadharwa nekushanduka kwemsL1 ribosomal protein itsva.Muchidzidzo ichi, takaona kuti E. cuniculi ribosome yakagadzirawo imwe ribosomal RNA mimic protein semuripo unooneka wekurasikirwa kweES19L.Zvakadaro, msL2 (ikozvino yakatsanangurwa seyekufungidzira ECU06_1135 puroteni) uye msL1 ane mavambo akasiyana uye evolutionary mabviro.c Uku kuwanikwa kwechizvarwa chekushanduka-shanduka kusina hukama msL1 uye msL2 ribosomal mapuroteni anoratidza kuti kana ribosomes ikaunganidza zvinokuvadza kuchinja muRRNA yavo, vanogona kuwana mazinga asati amboonekwa ekuumbwa kwakasiyana-siyana mune chero chikamu chidiki chezvipenyu zvine hukama.Kuwanikwa uku kunogona kubatsira kujekesa kwakabva uye kushanduka kweiyo mitochondrial ribosome, iyo inozivikanwa nekudzikiswa kwayo zvakanyanya rRNA uye kusiyanisa kusiri kwemaitiro ekuumbwa kweprotein mumarudzi ese.
Takazofananidza msL2 protein neprotein yakambotsanangurwa msL1, iyo chete inozivikanwa microsporidia-specific ribosomal protein inowanikwa muV. necatrix ribosome.Taida kuyedza kana msL1 uye msL2 zvine hukama.Ongororo yedu yakaratidza kuti msL1 uye msL2 inobata mhango mumwechete mune ribosomal chimiro, asi ine akasiyana ekutanga uye epamusoro zvimiro, izvo zvinoratidza yavo yakazvimirira yekushanduka-shanduka (Fig. 6).Saka, kuwana kwataita msL2 kunopa humbowo hwekuti mapoka ezvipenyu zveeukaryotic zvinokwanisa kushanduka zvakasununguka mapuroteni eribosomal akasarudzika kutsiva kurasikirwa kwezvidimbu zveRRNA.Kuwana uku kunoonekwa mukuti cytoplasmic eukaryotic ribosomes yakawanda ine mapuroteni asingachinji, kusanganisira mhuri imwechete ye81 ribosomal proteins.Kuonekwa kwe msL1 uye msL2 muzvikamu zvakasiyana-siyana zve microsporidia mukupindura kurasikirwa kwezvikamu zveRRNA zvakawedzerwa zvinoratidza kuti kuderedzwa kweparasite's molecular architecture kunokonzera kuti maparasite atsvage muripo wekuchinja, izvo zvinogona kupedzisira zvaita kuti vawanikwe mumarudzi akasiyana-siyana.zvimiro.
Pakupedzisira, pakazopedzwa modhi yedu, takaenzanisa kuumbwa kweE. cuniculi ribosome neyakafanotaurwa kubva mukutevedzana kwegenome.Mapuroteni akati wandei eribosomal, anosanganisira eL14, eL38, eL41, uye eS30, aimbofungidzirwa kuti akange asipo kubva kuE. cuniculi genome nekuda kwekushayikwa kuri pachena kwemahomologues kubva kuE. cuniculi genome.Kurasika kwemapuroteni akawanda eribosomal kunofungidzirwawo mune mamwe akawanda akaderedzwa zvakanyanya intracellular parasites uye endosymbionts.Semuenzaniso, kunyangwe mabhakitiriya mazhinji akasununguka ane mhuri imwechete ye54 ribosomal mapuroteni, gumi nerimwe chete emhuri dzeprotein idzi dzine mahomologues anoonekwa mune imwe neimwe yakaongororwa genome yemabhakitiriya anorambidzwa.Mukutsigira pfungwa iyi, kurasikirwa kweprotein yeribosomal kwave kuchionekwa muV. necatrix uye P. locustae microsporidia, iyo isina eL38 uye eL4131,32 mapuroteni.
Zvakadaro, zvimiro zvedu zvinoratidza kuti eL38, eL41, uye eS30 chete ndidzo dzakarasika muE. cuniculi ribosome.Iprotein eL14 yakachengetwa uye chimiro chedu chakaratidza kuti nei puroteni iyi isingagoni kuwanikwa mukutsvaga kwehomology (Fig. 7).MuE. cuniculi ribosomes, mazhinji eL14 inosunga nzvimbo inorasika nekuda kwekuora kweRRNA-amplified ES39L.Mukushaikwa kweES39L, eL14 yakarasikirwa nehuwandu hwechipiri chimiro, uye 18% chete yeL14 sequence yakanga yakafanana muE. cuniculi uye S. cerevisiae.Kuchengetedzwa kwakashata uku kunoshamisa nekuti kunyangwe Saccharomyces cerevisiae neHomo sapiens — zvipenyu zvakasimukira makore bhiriyoni 1.5 — zvinogovera zvinopfuura 51% yezvakasara zvakafanana muEL14.Uku kurasikirwa kusinganzwisisike kwekuchengetedza kunotsanangura kuti sei E. cuniculi eL14 parizvino ichinzi iyo putative M970_061160 protein uye kwete seL1427 ribosomal protein.
uye Iyo Microsporidia ribosome yakarasikirwa neES39L rRNA yekuwedzera, iyo yakabvisa zvishoma eL14 ribosomal protein binding site.Mukusavapo kweES39L, iyo eL14 microspore protein inosangana nekurasikirwa kwechipiri chimiro, umo iyo yekare rRNA-binding α-helix inopera kuita shoma urefu loop.b Multiple sequence alignment inoratidza kuti eL14 protein yakachengetedzwa zvakanyanya mueukaryotic marudzi (57% sequence identity pakati pe mbiriso nehomologues yevanhu), asi isina kuchengetedzwa uye yakasiyana-siyana mu microsporidia (umo isingasviki 24% yezvakasara zvakafanana ne eL14 homologue).kubva kuS. cerevisiae kana H. sapiens).Iyi yakashata kutevedzana kwekuchengetedza uye kushanduka kwechimiro chechipiri kunotsanangura kuti nei eL14 homologue isati yambowanikwa muE. cuniculi uye nei puroteni iyi inofungidzirwa kuti yakarasika muE. cuniculi.Kusiyana neizvi, E. cuniculi eL14 yakambotsanangurwa seprotein inoisa M970_061160.Kucherechedza uku kunoratidza kuti microsporidia genome diversity ikozvino yakanyanyisa: mamwe majini anofungidzirwa kuti akarasika mu microsporidia akachengetedzwa zvechokwadi, kunyange zvazvo ari mumhando dzakasiyana-siyana;pane kudaro, mamwe anofungidzirwa kuti ane macode emicrosporidia majini eprotein akanangana nehonye (semuenzaniso, puroteni yekufungidzira M970_061160) inonyatso kodhi yemapuroteni akasiyana-siyana anowanikwa mune mamwe eukaryotes.
Kuwana uku kunoratidza kuti rRNA denaturation inogona kutungamirira mukurasikirwa kukuru kwekutevedzana kwekuchengetedza mumapuroteni ari padyo neribosomal, zvichiita kuti mapuroteni aya asaonekwe pakutsvaga kwehomology.Nokudaro, tingafungidzire mwero chaiwoiwo wokushatiswa kwemamolekyulu muzvinhu zviduku zvegenome, sezvo mamwe mapuroteni anofungidzirwa kuva akarasika anopfuurira chaizvoizvo, kunyange zvazvo ari mumarudzi akachinjwa zvikuru.
Maparasite anogona sei kuchengetedza basa remashini avo emakemikari pasi pemamiriro ekunyanya kuderedza genome?Chidzidzo chedu chinopindura mubvunzo uyu nekutsanangura maitiro akaomarara emolecular (ribosome) eE. cuniculi, chipenyu chine rimwe remadiki eukaryotic genomes.
Izvo zvave zvichizivikanwa kweanoda kusvika makumi maviri emakore kuti mapuroteni uye mamorekuru eRNA muhutachiona hwehutachiona anowanzo siyana kubva kune avo homologous mamorekuru mumhando dzakasununguka-zvipenyu nekuti ivo havana nzvimbo dzekudzora mhando, dzakaderedzwa kusvika ku50% yehukuru hwadzo mumasikirini akasununguka, nezvimwewo.machinjiro mazhinji anopedza simba anokanganisa kupeta nekushanda.Semuenzaniso, ribosomes ezvisikwa zviduku zvejenome, kusanganisira akawanda intracellular parasites uye endosymbionts, inotarisirwa kushayiwa mapuroteni akawanda e ribosomal uye kusvika kune chikamu chimwe muzvitatu cheRRNA nucleotides kana ichienzaniswa nemhando yehupenyu yakasununguka 27, 29, 30, 49. Zvisinei, nzira iyo mamorekuru aya anoshanda nayo mukati mechikamu chikuru chekuongorora chinoramba chiripo.
Kudzidza kwedu kunoratidza kuti chimiro che macromolecules chinogona kuratidza zvinhu zvakawanda zvekushanduka-shanduka izvo zvakaoma kubvisa kubva kune tsika dzekare dzekuenzanisa genomic zvidzidzo zve intracellular parasites nezvimwe zvipenyu zvinorambidzwa (Supplementary Fig. 7).Semuenzaniso, muenzaniso weEL14 protein unoratidza kuti isu tinogona kuwedzeredza iyo chaiyo dhigirii yekuora kweiyo molecular apparatus muparasitic marudzi.Encephalitic parasites zvino vanotenda kuti vane mazana e microsporidia-specific genes.Zvakadaro, mhedzisiro yedu inoratidza kuti mamwe eaya anoita seakananga majini angori akasiyana zvakanyanya emajini anowanikwa mune mamwe eukaryotes.Uyezve, iyo msL2 puroteni inoratidza maitiro atinotarisisa mapuroteni matsva eribosomal uye tisingatarisire zviri mukati meparasitic molecular machine.Muenzaniso wemamorekuru madiki unoratidza maitiro atinogona kufuratira magadzirirwo akanyanya muparasitic molecular maitiro anogona kuapa maitiro matsva ebhayoloji.
Zvikatorwa pamwechete, mhedzisiro iyi inovandudza manzwisisiro edu emusiyano uripo pakati pezvimiro zvemamorekuru ezvipenyu zvinorambidzwa nezvinobatika pamwe neazvo mune zvipenyu zvinorarama zvakasununguka.Isu tinoratidza kuti michina yemamorekuru, yaifungidzirwa kwenguva refu kuti yakaderedzwa, yakareruka, uye iri pasi pekuchinja kwakasiyana-siyana kunopedza simba, pane kudaro ine seti yezvimiro zvisingatarisirwi zvisina kujairika.
Nekune rumwe rutivi, zvimedu zvisina-bulky rRNA uye zvimedu zvakasanganiswa zvatakawana mu ribosomes eE. cuniculi zvinoratidza kuti kuderedzwa kwegenome kunogona kuchinja kunyange zvikamu izvo zvemakomisheni ekutanga mamolecular akachengetedzwa muzvikamu zvitatu zvehupenyu - mushure memakore anoda kusvika 3.5 bhiriyoni.kushanduka kwakazvimirira kwemarudzi.
Zvimedu zvisina bulge uye zvakasanganiswa rRNA muE. cuniculi ribosomes zvinonyanya kufarira muchiedza chezvidzidzo zvekare zveRNA mamorekuru muendosymbiotic bacteria.Semuenzaniso, mu aphid endosymbiont Buchnera aphidicola, rRNA uye tRNA mamorekuru akaratidzwa kuva ane zvimiro zvinonzwa tembiricha nekuda kweA+T kuumbwa kwe bias uye chikamu chepamusoro chevasiri-canonical base pairs20,50.Idzi shanduko muRNA, pamwe nekushandurwa kweprotein molecules, iko zvino inofungidzirwa kuti inokonzera kudarika kwe endosymbionts kune vanobatana uye kusakwanisa kwe endosymbionts kutamisa kupisa 21, 23.Kunyangwe parasitic microsporidia rRNA ine shanduko yakasarudzika, chimiro chekuchinja uku chinoratidza kuti kudzikisira kugadzikana kwekupisa uye kutsamira kwepamusoro pamapuroteni echaperone kungave kwakajairwa mamorekuru eRNA muzvisikwa zvine genomes dzakaderedzwa.
Nekune rumwe rutivi, zvimiro zvedu zvinoratidza kuti parasite microsporidia yakave yakasarudzika kugona kuramba yakachengetedzwa yakachengetedzwa rRNA uye mapuroteni zvimedu, kukudziridza kugona kushandisa akawanda uye anowanikwa nyore metabolites madiki semamisikirwo ekumisikidza eRNA yakaora uye mapuroteni zvimedu.Kuparara kwechimiro chemolecular..Maonero aya anotsigirwa nenyaya yekuti mamorekuru madiki anobhadhara kurasikirwa kwezvimedu zveprotein mu rRNA uye ribosomes eE. cuniculi anosunga kune microsporidia-chaiwo masara muL15 uye eL30 mapuroteni.Izvi zvinoratidza kuti kusungirirwa kwemamorekuru maduku kune ribosomes kunogona kuva chigadzirwa chekusarudzwa kwakanaka, umo Microsporidia-specific mutations mu ribosomal proteins yakasarudzwa nokuda kwekukwanisa kwavo kuwedzera kuwirirana kwe ribosomes kune ma molecules maduku, izvo zvinogona kutungamirira kune zvakanyanya kushanda ribosomal organisms.Kuwanikwa kwacho kunoratidza hungwaru hutsva muchimiro chemolecular ye microbial parasites uye inotipa kunzwisisa kuri nani kwemaparasite molecular zvimiro zvinochengetedza basa razvo kunyangwe kushanduka kwekuchinja.
Parizvino, kuzivikanwa kweaya mamorekuru madiki anoramba asina kujeka.Hazvisi pachena kuti sei kutaridzika kweaya mamorekuru madiki mune ribosomal chimiro kwakasiyana pakati pe microsporidia marudzi.Kunyanya, hazvisi pachena kuti nei nucleotide inosunga ichionekwa mu ribosomes yeE. cuniculi uye P. locustae, uye kwete mu ribosomes yeV. necatrix, pasinei nekuvapo kweF170 yakasara mu eL20 uye K172 mapuroteni eV. necatrix.Kudzima uku kunogona kukonzerwa nekusara 43 uL6 (iri pedyo nehomwe inosunga nucleotide), iyo inonzi tyrosine muV. necatrix uye kwete threonine muE. cuniculi uye P. locustae.Iyo yakakura inonhuhwirira yedivi cheni yeTyr43 inogona kukanganisa nucleotide inosunga nekuda kwekupindirana kwesteric.Neimwe nzira, iyo inooneka nucleotide deletion inogona kunge yakakonzerwa nekugadziriswa kwakaderera kwe cryo-EM imaging, iyo inodzivisa kuenzanisira kweV. necatrix ribosomal fragments.
Ukuwo, basa redu rinoratidza kuti kuparara kwegenome kunogona kuva simba rekutanga.Kunyanya, chimiro cheE. cuniculi ribosome chinoratidza kuti kurasikirwa kweRRNA uye mapuroteni zvimedu mu microsporidia ribosome kunogadzira kushanduka kwekushanduka kunokurudzira kuchinja kweribosome chimiro.Aya akasiyana anoitika kure nenzvimbo inoshanda yeribosome uye anoita senge anobatsira kuchengetedza (kana kudzoreredza) yakakwana ribosome gungano ringazovhiringwa nekuderedzwa rRNA.Izvi zvinoratidza kuti hunyanzvi hukuru hwemicrosporidia ribosome hunoratidzika kunge hwakashanduka kuita kudiwa kwebuffer gene drift.
Zvichida izvi zvinonyatsoratidzwa ne nucleotide kusunga, iyo isina kumboonekwa mune zvimwe zvipenyu kusvika ikozvino.Ichokwadi chokuti nucleotide-binding residues iripo mune yakajairika microsporidia, asi kwete mune mamwe eukaryotes, inoratidza kuti nucleotide-inosunga nzvimbo haisi zvisaririra zvakamirira kunyangarika, kana nzvimbo yekupedzisira yeRRNA kuti idzoserwe kune imwe neimwe nucleotides.Pane kudaro, saiti ino inoita senge chinhu chinobatsira chinogona kunge chakashanduka pamusoro peakati wandei esarudzo yakanaka.Nucleotide inosunga nzvimbo inogona kunge iri-chigadzirwa chekusarudzwa kwechisikigo: kana ES39L yakasvibiswa, microsporidia inomanikidzwa kutsvaga mubhadharo kuti udzorere zvakakwana ribosome biogenesis pasina ES39L.Sezvo iyi nucleotide ichikwanisa kutevedzera mamorekuru eiyo A3186 nucleotide muES39L, iyo nucleotide molecule inova chivakwa cheribosome, chinosungirirwa icho chinowedzerwa nekuvandudzwa kweiyo eL30 kutevedzana.
Nezvekushanduka kwema molecular of intracellular parasites, chidzidzo chedu chinoratidza kuti masimba eDarwinan natural selection uye genetic drift yekuora kwegenome haashande mukufanana, asi anotenderera.Chekutanga, genetic drift inobvisa zvakakosha zvebiomolecules, zvichiita kuti muripo unodiwa zvakanyanya.Chete kana zvipembenene zvikagutsa chido ichi kuburikidza nekusarudza kwemusikirwo kwaDarwin ndiko kunoita kuti macromolecules avo ave nemukana wekukudziridza hunhu hwavo hunoyemurika uye hutsva.Zvinonyanya kukosha, shanduko yenzvimbo dzinosunga nucleotide muE. cuniculi ribosome inoratidza kuti iyi nzira yekurasikirwa-ku-kuwana yekushanduka kwema molecular haingokonzerese kuchinja kwakashata, asi dzimwe nguva inopa mabasa matsva paparasitic macromolecules.
Pfungwa iyi inopindirana nedzidziso yaSewell Wright yekufamba yakaenzana, iyo inotaura kuti hurongwa hwakasimba hwekusarudzwa kwezvisikwa hunoganhura kugona kwezvipenyu kugadzira 51,52,53.Zvisineyi, kana genetic drift ikakanganisa kusarudzwa kwechisikigo, madhirifiti aya anogona kuburitsa shanduko iyo isiri iyo pachayo inochinjika (kana kunyange inokuvadza) asi inotungamira kune dzimwe shanduko dzinopa kusimba kwepamusoro kana chiitiko chitsva chebhayoloji.Chimiro chedu chinotsigira pfungwa iyi nekuratidza kuti iwowo mhando yekuchinja inoderedza kupeta uye kushanda kwebiomolecule inoita kunge ndiyo inonyanya kukonzera kuvandudzwa kwayo.Mukuwirirana ne-win-win evolutionary model, chidzidzo chedu chinoratidza kuti kuora kwegenome, kunowanzoonekwa senzira yekuparara, ihwowo mutyairi mukuru wezvitsva, dzimwe nguva uye zvichida kunyange kazhinji kubvumira macromolecules kuwana mabasa matsva eparasitic.vanogona kuzvishandisa.