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Ihindagurika ry’udukoko duto duto rikubiyemo guhangana hagati y’uburyo bwo guhitamo karemano, butuma udukoko dutera imbere, n’ihindagurika ry’uturemangingo, rituma udukoko dutakaza imiterere y’uturemangingo no kwegeranya impinduka zangiza. Aha, kugira ngo twumve uburyo uku guhangana kubaho ku rugero rwa macromolecule imwe, turasobanura imiterere ya cryo-EM ya ribosome ya Encephalitozoon cuniculi, ikinyabuzima cya eukaryotic gifite imwe mu ngirabuzimafatizo ntoya mu miterere. Kugabanuka gukabije kwa rRNA muri E. cuniculi ribosomes biherekezwa n’impinduka zidasanzwe mu miterere, nko guhinduka kw’ibihuza bya rRNA na rRNA bitari bizwi mbere nta bubyimba. Byongeye kandi, E. cuniculi ribosome yarokotse ibura ry’uduce twa rRNA na poroteyine binyuze mu guteza imbere ubushobozi bwo gukoresha molecule nto nk’imiterere y’uduce twa rRNA na poroteyine zangiritse. Muri rusange, tugaragaza ko imiterere ya molekile imaze igihe kinini itekerezwa ko yagabanutse, yangiritse, kandi ihura n’impinduka zikomeye zifite uburyo bwinshi bwo kuyisubiza butuma ikomeza gukora nubwo yagabanutse cyane.
Kubera ko amatsinda menshi y’udukoko duto dufite ibikoresho byihariye bya molekile kugira ngo dukoreshe ibyo dutunze, akenshi tugomba guteza imbere uburyo butandukanye bwo kuvura amatsinda atandukanye y’udukoko1,2. Ariko, ibimenyetso bishya bigaragaza ko bimwe mu bice by’imihindagurikire y’udukoko bihurirana kandi ahanini bikaba byagenwa, bigaragaza ko hari ishingiro ry’uburyo bugari bwo kuvura udukoko duto3,4,5,6,7,8,9.
Ubushakashatsi bwakozwe mbere bwagaragaje inzira isanzwe y’ubwihindurize mu dukoko duto twitwa kugabanya genome cyangwa kubora kwa genome10,11,12,13. Ubushakashatsi buriho bwerekana ko iyo udukoko duto dusize ubuzima bwacu bwo kubaho tugahinduka udukoko two mu ngirabuzima fatizo (cyangwa endosymbionts), genome zabo zigenda zihinduka buhoro buhoro ariko zitangaje mu myaka miliyoni9,11. Mu buryo buzwi nka kubora kwa genome, udukoko duto dukusanya impinduka mbi zihindura genome nyinshi zari zisanzwe zihambaye zikaba pseudogenes, bigatuma gene itakaza buhoro buhoro no gusenyuka kwa mutation14,15. Uku gusenyuka gushobora gusenya kugeza kuri 95% by'uturemangingo mu turemangingo twa kera cyane ugereranije n'ubwoko bw'ibinyabuzima bifitanye isano rya bugufi. Bityo, iterambere ry'udukoko duto duto mu ngirabuzima fatizo ni intambara hagati y'imbaraga ebyiri zihanganye: Guhitamo karemano kwa Darwin, biganisha ku kunoza udukoko, no gusenyuka kwa genome, bigatuma udukoko twibagirana. Uburyo agakoko gashobora kuva muri ubu bushyamirane no kugumana imikorere y'imiterere yatwo ntabwo birasobanutse neza.
Nubwo uburyo bwo kwangirika kwa genome butasobanuka neza, bisa nkaho biterwa ahanini no kwiyongera kenshi kwa genome. Kubera ko udukoko tuba mu duce duto, tudahuje igitsina, kandi dufite imiterere mike, ntidushobora gukuraho neza impinduka mbi rimwe na rimwe ziba mu gihe cyo kwibasira ADN. Ibi bituma habaho kwiyongera ku buryo budasubirwaho kw'impinduka mbi no kugabanuka kwa genome y'udukoko. Kubera iyo mpamvu, agakoko ntigatakaza gusa imiterere itagikenewe kugira ngo kabeho mu ngirabuzima fatizo. Ni ukudashobora kwa amoko y'udukoko gukuraho neza impinduka mbi zibaho rimwe na rimwe bituma izi mpinduka ziyongera muri genome yose, harimo na jeni zabo z'ingenzi.
Uburyo bwinshi dusobanukirwa ku kugabanuka kwa genome bushingiye gusa ku kugereranya uruhererekane rwa genome, hibandwa cyane ku mpinduka mu ngirabuzimafatizo nyazo zikora imirimo yo kubungabunga inzu kandi zikaba ari zo zishobora guterwa n’imiti. Ubushakashatsi bwo kugereranya bwagaragaje ko umutwaro w’impinduka za mikorobe zo mu ngirabuzimafatizo zibangamira imiterere y’uturemangingo usa n’aho utuma poroteyine na aside nucleic zitandukana kandi zigaterana, bigatuma zikenera cyane chaperone kandi zikagira ingaruka zikomeye ku bushyuhe19,20,21,22,23. Byongeye kandi, udukoko dutandukanye—twigenga rimwe na rimwe dutandukanijwe n’imyaka miliyari 2.5—twahuye n’igihombo nk’iki cy’ibigo bigenzura ubuziranenge mu gukora poroteyine5,6 no mu buryo bwo gusana ADN24. Ariko, nta byinshi bizwi ku ngaruka z’imibereho yo mu ngirabuzimafatizo ku yindi miterere yose ya macromolecules za selile, harimo no guhinduka kwa molekile ku mutwaro wiyongera w’impinduka zangiza.
Muri iki gitabo, kugira ngo dusobanukirwe neza imiterere ya poroteyine na aside nucleic za mikorobe zo mu ngirabuzimafatizo, twamenye imiterere ya ribosomu z’udukoko two mu ngirabuzimafatizo Encephalitozoon cuniculi. E. cuniculi ni ibinyabuzima bisa n’ibihumyo biri mu itsinda rya mikorosporidia zisanzwe zifite genome ntoya cyane za eukaryotic bityo zikoreshwa nk'ibinyabuzima by'icyitegererezo mu kwiga kwangirika kwa genome25,26,27,28,29,30. Vuba aha, imiterere ya ribosomu ya cryo-EM yagenwe ku ngirabuzimafatizo za Microsporidia, Paranosema loctae, na Vairimorpha necatrix31,32 (genome ya ~3.2 Mb). Izi ngirabuzimafatizo zigaragaza ko gutakaza rRNA amplification kwishyurwa no guteza imbere imikoranire mishya hagati ya poroteyine za ribosomu zegeranye cyangwa kubona poroteyine nshya za msL131,32 ribosomu. Ubwoko bwa Encephalitozoon (genome ~ miliyoni 2.5 bp), hamwe na Ordospora ya hafi cyane, bigaragaza urugero rwo hejuru rw'igabanuka rya genome muri eukaryotes - bafite genes zitarenze 2000 zikora poroteyine, kandi byitezwe ko ribosome zabo zitari gusa zidafite ibice bya rRNA byo kwaguka (ibice bya rRNA bitandukanya ribosomes za eukaryotic na ribosomes za bagiteri) kandi zifite poroteyine enye za ribosomal bitewe n'uko zidafite homologues muri genome ya E. cuniculi26,27,28. Kubwibyo, twanzuye ko ribosome ya E. cuniculi ishobora kugaragaza ingamba zitari zizwi zo guhindura molekile kugira ngo irandure genome.
Imiterere yacu ya cryo-EM igaragaza ribosomu ntoya cyane ya eukaryotic cytoplasmic yagaragajwe kandi itanga ibisobanuro ku buryo urwego rw'ikirenga rwo kugabanuka kwa genome rugira ingaruka ku miterere, guterana, no kwiyongera kw'imikorere ya molekile igize akaremangingo. Twasanze ribosomu ya E. cuniculi inyuranyije n'amahame menshi ya RNA yo gukurura no guterana kwa ribosomu, maze tuvumbura poroteyine nshya ya ribosomu itari izwi mbere. Mu buryo butunguranye, twerekanye ko mikorosporidia ribosomu zahinduye ubushobozi bwo gufata molekile nto, kandi tugatekereza ko gucikamo ibice muri rRNA na poroteyine bitera udushya twinshi dushobora gutanga imiterere myiza kuri ribosomu.
Kugira ngo twongere ubumenyi bwacu ku mihindukire ya poroteyine na aside nucleic mu binyabuzima biri mu ngirabuzimafatizo, twahisemo gutandukanya spores za E. cuniculi mu miterere y’uturemangingo tw’inyamabere twanduye kugira ngo twoze ribosomes zazo kandi tumenye imiterere y’izi ribosomes. Biragoye kubona umubare munini wa microsporidia ziterwa n’udukoko kuko microsporidia idashobora guhingwa mu buryo bw’intungamubiri. Ahubwo, zikura kandi zikororoka gusa mu turemangingo tw’umubiri. Kubwibyo, kugira ngo tubone biomass ya E. cuniculi yo gutunganya ribosome, twanduje umuyoboro wa RK13 w’uturemangingo tw’impyiko tw’inyamabere E. cuniculi maze dutunganya utwo turemangingo twanduye mu gihe cy’ibyumweru byinshi kugira ngo E. cuniculi ikure kandi igwire. Dukoresheje uruhande rumwe rw’uturemangingo twanduye rufite hafi igice cya metero kare, twashoboye gutunganya spores za Microsporidia zigera kuri mg 300 no kuzikoresha mu gutandukanya ribosomes. Hanyuma twavuguruye spores zasukuwe dukoresheje amasaro y’ikirahure maze dutandukanya ribosomes mbisi dukoresheje uburyo bwo gutandukanya lysates za polyethylene glycol. Ibi byatumye tubona hafi µg 300 za ribosomes mbisi za E. cuniculi kugira ngo zikoreshwe mu gusesengura imiterere yazo.
Hanyuma twakusanyije amashusho ya cryo-EM dukoresheje ingero za ribosome zavuyemo maze dutunganya ayo mashusho dukoresheje udupfukamunwa duhuye n’agace gato ka ribosomal, umutwe muto w’agace gato, n’agace gato gato. Muri iki gikorwa, twakusanyije amashusho y’uduce twa ribosomal tugera ku 108.000 n’amashusho ya cryo-EM yabazwe hamwe n’umusaruro wa 2.7 Å (Ishusho y’inyongera 1-3). Hanyuma twakoresheje amashusho ya cryoEM kugira ngo dushushanye rRNA, poroteyine ya ribosomal, na factor ya hibernation Mdf1 ijyanye na E. cuniculi ribosomal (Ishusho ya 1a, b).
Imiterere ya ribosome ya E. cuniculi iri mu buryo buhuriweho na factor ya hibernation Mdf1 (pdb id 7QEP). b Ikarita ya factor ya hibernation Mdf1 ijyanye na ribosome ya E. cuniculi. c Ikarita y'imiterere ya kabiri igereranya rRNA yavuguruwe mu bwoko bwa Microsporidian n'imiterere ya ribosomal izwi. Utu duce twerekana aho ibice bya rRNA byazamuwe (ES) n'ahantu hakora ha ribosomal, harimo n'ahantu ho gusesengura (DC), sarcinicin loop (SRL), n'ikigo cya peptidyl transferase (PTC). d Ubucucike bwa electron bujyanye n'ikigo cya peptidyl transferase cya ribosome ya E. cuniculi bugaragaza ko iki kibanza cya catalytic gifite imiterere imwe muri parasite ya E. cuniculi n'ibirimo, harimo na H. sapiens. e, f Ubucucike bwa electron bujyanye n'aho ikigo gisobanura (e) giherereye hamwe n'imiterere y'aho ikigo gisobanura (f) bigaragaza ko E. cuniculi ifite ibisigazwa bya U1491 aho kuba A1491 (E. coli numbering) mu zindi eukaryote nyinshi. Iri hinduka ryerekana ko E. cuniculi ishobora kuba ifite ubushobozi bwo kwandura antibiyotike zireba aha hantu hakora.
Bitandukanye n’imiterere ya V. necatrix na P. loccitae ribosomes zari zisanzweho (imiterere yombi ihagarariye umuryango umwe wa Nosematidae kandi isa cyane), 31,32 E. cuniculi ribosomes zinyura mu nzira nyinshi zo gucikamo ibice bya rRNA na poroteyine. Gucikamo ibice (Ishusho y'inyongera 4-6). Muri rRNA, impinduka zikomeye cyane zari zirimo gutakaza burundu igice cya 25S rRNA ES12L cyazamuwe no kwangirika kw'igice cya h39, h41, na H18 helices (Ishusho ya 1c, Ishusho y'inyongera 4). Muri poroteyine za ribosomes, impinduka zikomeye cyane zari zirimo gutakaza burundu poroteyine ya eS30 no kugabanuka kwa poroteyine za eL8, eL13, eL18, eL22, eL29, eL40, uS3, uS9, uS14, uS17, na eS7 (Ishusho y'inyongera 4, 5).
Bityo, igabanuka rikomeye rya genome z'ubwoko bwa Encephalotozoon/Ordospora rigaragarira mu miterere ya ribosome yazo: E. cuniculi ribosomes zigira igihombo gikomeye cya poroteyine muri eukaryotic cytoplasmic ribosomes bitewe n'imiterere y'imiterere, kandi nta n'uduce twa rRNA na poroteyine dufite tubitswe cyane atari muri eukaryotes gusa, ahubwo no mu nzego eshatu z'ubuzima. Imiterere ya E. cuniculi ribosome itanga icyitegererezo cya mbere cya molekile kuri izi mpinduka kandi igaragaza ibyabaye mu ihindagurika ry'ikirere byirengagijwe haba mu bushakashatsi bugereranya genome ndetse no mu bushakashatsi ku miterere ya biomolecular mu ngirabuzima fatizo (Ishusho y'inyongera ya 7). Hasi, turasobanura buri kimwe muri ibi bintu hamwe n'inkomoko yabyo ishobora kuba ihindagurika ndetse n'ingaruka zishobora kugira ku mikorere ya ribosome.
Hanyuma twasanze, uretse uduce duto twa rRNA, E. cuniculi ribosomes zifite impinduka za rRNA ahantu hamwe mu hakorerwa. Nubwo urwego rwa peptidyl transferase rwa E. cuniculi ribosome rufite imiterere imwe n’izindi ribosomes za eukaryotic (Ishusho ya 1d), urwego rwo gusesengura imiterere ruratandukanye bitewe n’impinduka z’uruhererekane kuri nucleotide 1491 (E. coli numbering, Ishusho ya 1e, f). Iki gitekerezo ni ingenzi kuko aho ribosomes za eukaryotic ziherereye ubusanzwe harimo ibisigazwa bya G1408 na A1491 ugereranije n’ibisigazwa byo mu bwoko bwa bagiteri A1408 na G1491. Iri hinduka rishingiye ku buryo butandukanye bwo kumva ribosomes za bagiteri na eukaryotic ku muryango wa aminoglycoside wa antibiyotike za ribosomal n’utundi duce duto twibasira aho dusesengura imiterere. Ahantu handitse E. cuniculi ribosome, ibisigazwa bya A1491 byasimbuwe na U1491, bishobora gutuma habaho uburyo bwihariye bwo guhuza molecule ntoya zireba aha hantu hakora. Ubwoko bumwe bwa A14901 buboneka no mu zindi microsporidia nka P. loccitae na V. necatrix, bigaragaza ko ikwirakwiriye mu moko ya microsporidia (Ishusho ya 1f).
Kubera ko ingero zacu za ribosome ya E. cuniculi zakuwe mu turemangingo tudakora neza mu mikorere y’umubiri, twagerageje ikarita ya cryo-EM ya E. cuniculi kugira ngo tumenye uko ribosome ifatana mbere mu gihe cy’imihangayiko cyangwa inzara. Ibintu byo mu gihe cy’ubushyuhe 31,32,36,37, 38. Twahuje imiterere ya ribosome ihora ihindagurika n’ikarita ya cryo-EM ya ribosome ya E. cuniculi. Mu gufunga, ribosome za S. cerevisiae zakoreshejwe mu buryo buhuriweho na factor ya hibernation Stm138, ribosome z’inzitane mu buryo buhuriweho na factor ya Lso232, na ribosome za V. necatrix mu buryo buhuriweho na factor ya Mdf1 na Mdf231. Muri icyo gihe, twasanze ubucucike bwa cryo-EM buhuye na factor ya Mdf1 isigaye. Kimwe na Mdf1 ihambira kuri ribosome ya V. necatrix, Mdf1 inahambira kuri ribosome ya E. cuniculi, aho ifunga aho ribosome iherereye, bishobora gufasha gutuma ribosome ziboneka iyo udukoko tw’udukoko tuba tudakora neza iyo umubiri udakora (Ishusho ya 2).
Mdf1 ifunga aho ribosome iherereye, bigaragara ko ifasha mu guhagarika ribosome iyo udukoko tw’udukoko tw’udukoko tutagikora. Mu miterere ya ribosome ya E. cuniculi, twasanze Mdf1 ikora ikintu kitari kizwi mbere cyahuye n’igiti cya ribosome cya L1, igice cya ribosome cyorohereza irekurwa rya tRNA idafunguye muri ribosome mu gihe cyo gukora poroteyine. Izi mibonano igaragaza ko Mdf1 yitandukanya na ribosome ikoresheje uburyo bumwe na tRNA idafunguye, bigatanga ibisobanuro bishoboka by’uburyo ribosome ikuraho Mdf1 kugira ngo yongere gukora poroteyine.
Ariko, imiterere yacu yagaragaje ko hari aho Mdf1 n'ukuguru kwa ribosome ya L1 bihurira (igice cya ribosome gifasha kurekura tRNA idafunguye muri ribosome mu gihe cyo gukora poroteyine). By'umwihariko, Mdf1 ikoresha uburyo bumwe n'igice cy'inkokora cya molecule ya tRNA idafunguye (Ishusho ya 2). Ubu buryo bwa molekile butazwi mbere bwagaragaje ko Mdf1 yitandukanya na ribosome ikoresheje uburyo bumwe na tRNA idafunguye, ibi bikaba bisobanura uburyo ribosome ikuraho ubu buryo bwo gutinda kugira ngo yongere gukora poroteyine.
Ubwo twakoraga icyitegererezo cya rRNA, twasanze ribosome ya E. cuniculi ifite ibice bya rRNA bipfunyitse mu buryo budasanzwe, ibyo twise rRNA ivanze (Ishusho ya 3). Muri ribosome zigize uturere dutatu tw'ubuzima, rRNA yivanga mu miterere aho rRNA nyinshi zishingiraho zigahuzwa cyangwa zigakorana na poroteyine za ribosomal38,39,40. Ariko, muri ribosome za E. cuniculi, rRNA zisa nkaho zinyuranyije n'iri hame ryo gupfunyika zihindura zimwe muri helices zazo mu duce twa rRNA tutarapfunyitse.
Imiterere ya H18 25S rRNA helix muri S. cerevisiae, V. necatrix, na E. cuniculi. Ubusanzwe, muri ribosomes zigize uturere dutatu tw’ubuzima, iyi linker yivanga mu helix ya RNA irimo ibisigazwa 24 kugeza kuri 34. Muri Microsporidia, mu buryo bunyuranye, iyi linker ya rRNA igabanuka buhoro buhoro ikaba ibisigazwa bibiri bifite umugozi umwe birimo ibisigazwa 12 gusa. Ibyinshi muri ibi bisigazwa bihura n’ibintu bishongesha. Ishusho igaragaza ko microsporidia ya parasite isa nkaho inyuranyije n’amahame rusange yo gupfunyika kwa rRNA, aho ishingiro rya rRNA rikunze guhuzwa n’izindi base cyangwa rikagira uruhare mu mikoranire ya rRNA na poroteyine. Muri microsporidia, bimwe mu bice bya rRNA bifata ipfundo ribi, aho helix ya rRNA yahoze iba igice gifite umugozi umwe cyagutse hafi ku murongo ugororotse. Kuba hari utu duce tudasanzwe bituma microsporidia rRNA ifata ibice bya rRNA bya kure ikoresheje umubare muto w’ishingiro rya RNA.
Urugero rutangaje rw'iyi mpinduka y'ubwihindurize ruboneka muri H18 25S rRNA helix (Ishusho ya 3). Mu moko kuva kuri E. coli kugeza ku bantu, ishingiro ry'iyi helix ya rRNA rigizwe na nucleotides 24-32, zigakora helix idasobanutse neza. Mu miterere ya ribosomal ya V. necatrix na P. locustae,31,32 ishingiro ry'ishingiro rya H18 helix ntiripfundikiye igice, ariko ishingiro rya nucleotide rirabikwa. Ariko, muri E. cuniculi iki gice cya rRNA kiba ishingiro rigufi cyane 228UUUGU232 na 301UUUUUUUUU307. Bitandukanye n'ibice bisanzwe bya rRNA, ibi bihuza birimo uridine ntibihuza cyangwa ngo bihuze cyane na poroteyine za ribosomal. Ahubwo, bifata imiterere ifunguye kandi ifunguye neza aho imigozi ya rRNA irambuye hafi ku buryo bugororotse. Iyi miterere yagutse isobanura uburyo E. cuniculi ikoresha base 12 za RNA gusa kugira ngo yuzuze icyuho cya 33 Å kiri hagati ya helices za H16 na H18 rRNA, mu gihe izindi nyoni zikenera nibura base rRNA ebyiri kugira ngo yuzuze icyuho.
Bityo, dushobora kugaragaza ko, binyuze mu gupfunyika nabi mu buryo butari bwiza, mikorosiporodiya za parasite zashyizeho ingamba zo gupfunyika ndetse n'ibice bya rRNA bikomeje kubikwa mu buryo bunini mu moko yose mu bice bitatu by'ubuzima. Uko bigaragara, mu kwegeranya impinduka zihindura helices za rRNA mo ibihuza bigufi bya poly-U, E. cuniculi ishobora gukora ibice bidasanzwe bya rRNA birimo nucleotides nke zishoboka kugira ngo bifatanye ibice bya rRNA biri kure. Ibi bifasha gusobanura uburyo mikorosiporodiya yagabanutse cyane mu miterere yabyo y'ibanze ya molekile idatakaje imiterere n'imikorere yabyo.
Ikindi kintu kidasanzwe cya E. cuniculi rRNA ni ukugaragara kwa rRNA nta bubyimba (Ishusho ya 4). Uduce tw’uturemangingo ni utunyangingo tw’ingirabuzimafatizo tudafite ibice by’ibanze biva muri helix ya RNA aho kwihishamo. Inyinshi mu duce twa rRNA dukora nk'uduce tw’ingirabuzimafatizo, bigafasha gufata poroteyine za ribosomal zegeranye cyangwa ibindi bice bya rRNA. Amwe mu matsinda akora nk'udukingirizo, bigatuma helix ya rRNA ihinduka kandi igapfunyika neza kugira ngo poroteyine ikore neza 41.
a Ingano ya rRNA (S. cerevisiae numbering) ntabwo iboneka mu miterere ya E. cuniculi ribosome, ariko iboneka mu zindi eukaryotes nyinshi za E. coli, S. cerevisiae, H. sapiens, na E. cuniculi internal ribosomes. Parasite ntiziba zifite imiterere myinshi ya rRNA ya kera kandi ibungabunzwe cyane. Uku gukomera gutuma imiterere ya ribosome ikomera; bityo, kuba zitaboneka muri microsporidia bigaragaza ko rRNA igenda igabanuka mu mikorere ya microsporidia parasite. Ugereranije n'imiti ya P (imiti ya L7/L12 muri bagiteri) bigaragaza ko kubura kwa rRNA bumps rimwe na rimwe bihurirana no kugaragara kwa tubumps dushya iruhande rw'udusimba twatakaye. Helix ya H42 muri 23S/28S rRNA ifite tubumps ya kera (U1206 muri Saccharomyces cerevisiae) ibarirwa mu myaka miliyari 3.5 bitewe n'uburinzi bwayo mu nzego eshatu z'ubuzima. Muri microsporidia, ubu tubumps burakurwaho. Ariko, hagaragaye agahu gashya iruhande rw'agahu katakaye (A1306 muri E. cuniculi).
Igitangaje ni uko twasanze ribosome za E. cuniculi zidafite uduce twinshi twa rRNA tuboneka mu zindi moko, harimo uduce turenga 30 twabitswe mu zindi eukaryote (Ishusho ya 4a). Uku gutakaza bikuraho imikoranire myinshi hagati y’uduce duto twa ribosomal na helices zegeranye za rRNA, rimwe na rimwe bigatuma habaho imyobo minini muri ribosome, bigatuma ribosome ya E. cuniculi igira imyenge myinshi ugereranije na ribosome zisanzwe (Ishusho ya 4b). Cyane cyane, twasanze utu duce twinshi twatakaye mu miterere ya ribosome ya V. necatrix na P. locustae yari yarabonetse mbere, yirengagijwe n’isesengura ry’imiterere ryabanje31,32.
Hari igihe kubura kw'uturemangingo twa rRNA biherekezwa n'ivuka ry'uturemangingo dushya iruhande rw'uturemangingo twatakaye. Urugero, igiti cya ribosomal P kirimo umubyimba wa U1208 (muri Saccharomyces cerevisiae) warokotse kuva kuri E. coli kugera ku bantu bityo ukaba ufite imyaka miliyari 3.5. Mu gihe cyo gukora poroteyine, uyu mubyimba ufasha igiti cya P kugenda hagati y'imiterere ifunguye n'ifunze kugira ngo ribosome ibashe gushaka ibintu byo guhindura no kubigeza aho bikorera. Muri ribosome za E. cuniculi, uku gukuba ntiguhari; icyakora, gukuba gushya (G883) guherereye mu duce dutatu tw'ibanze gusa bishobora gufasha mu kugarura uburyo bwiza bwo koroherwa n'igiti cya P (Ishusho ya 4c).
Amakuru yacu kuri rRNA idafite uduce duto agaragaza ko kugabanya rRNA bitagarukira gusa ku gutakaza ibice bya rRNA ku buso bwa ribosome, ahubwo bishobora no kuba bifitanye isano n'ingirabuzimafatizo ya ribosome, bigatuma habaho inenge ya molekile yihariye itarasobanuka mu turemangingo tw’ubuzima. Hari ubwoko bw’ibinyabuzima bugaragara.
Nyuma yo gukora ibishushanyo bya poroteyine za ribosomal na rRNA, twasanze ibice bisanzwe bya ribosomal bidashobora gusobanura ibice bitatu by'ishusho ya cryo-EM. Ibice bibiri muri ibi ni molekile nto mu bunini (Ishusho ya 5, Ishusho y'inyongera ya 8). Igice cya mbere kiri hagati ya poroteyine za ribosomal uL15 na eL18 mu mwanya usanzwe ufatwa na C-terminus ya eL18, ifunze muri E. cuniculi. Nubwo tudashobora kumenya umwirondoro w'iyi molekile, ingano n'imiterere y'iyi kirwa cy'ubucucike bisobanurwa neza no kuba hari molekile za spermidine. Guhuza kwayo na ribosome bihagarikwa na mikorosporidia-specific mutations muri poroteyine za uL15 (Asp51 na Arg56), bisa nkaho byongera ubwiza bwa ribosome kuri iyi molekile nto, kuko bituma uL15 ipfunyika molekile nto mu buryo bwa ribosomal. Ishusho y'inyongera ya 2). 8, amakuru y'inyongera 1, 2).
Ishusho ya Cryo-EM igaragaza ko hari nucleotides hanze ya ribose ijyanye na ribosome ya E. cuniculi. Muri ribosome ya E. cuniculi, iyi nucleotide ifite umwanya umwe na nucleotide ya 25S rRNA A3186 (Saccharomyces cerevisiae numbering) mu zindi ribosome nyinshi za eukaryotic. b Mu miterere ya ribosomal ya E. cuniculi, iyi nucleotide iherereye hagati ya poroteyine za ribosomal uL9 na eL20, bityo bigatuza uburyo poroteyine ebyiri zikorana. Isesengura rya cd eL20 ryo kubungabunga uruhererekane mu moko ya microsporidia. Igiti cya phylogenetic cy’ubwoko bwa Microsporidia (c) hamwe no guhuza poroteyine ya eL20 (d) bigaragaza ko ibisigazwa bya nucleotide-binding F170 na K172 bibitswe muri Microsporidia nyinshi zisanzwe, usibye S. lophii, usibye Microsporidia ya mbere y’amashami, yagumanye ES39L rRNA yongerwa. Iyi shusho igaragaza ko ibisigazwa bya nucleotide-binding F170 na K172 biboneka gusa muri eL20 ya genome ya microsporidia yagabanutse cyane, ariko ntabwo biri mu zindi eukaryotes. Muri rusange, aya makuru agaragaza ko ribosomes za Microsporidian zakoze ahantu hahuza nucleotide hagaragara ko hahuza molekile za AMP kandi zikabukoresha mu gushimangira imikoranire ya poroteyine na poroteyine mu miterere ya ribosomal. Kubungabunga cyane aha hantu hahuza muri Microsporidia no kutagira ahandi muri eukaryotes bigaragaza ko aha hantu hashobora gutanga inyungu yo kubaho kuri Microsporidia. Bityo, agace gafata nucleotide muri microsporidia ribosome ntabwo gasa nkaho ari ikintu cyangiritse cyangwa iherezo rya rRNA yononekaye nkuko byasobanuwe mbere, ahubwo ni ingirakamaro mu ihindagurika ry’ibintu bitera microsporidia ribosome gufatana mu buryo butaziguye na molekile nto, ikazikoresha nk'inkingi z’inyubako za molekile. Ubu buvumbuzi butuma microsporidia ribosome iba ribosome yonyine izwiho gukoresha nucleotide imwe nk'inkingi y’inyubako yayo. f Inzira y’ihindagurika ry’ibintu ikomoka ku guhuza nucleotide.
Ubucucike bwa kabiri buri hasi bwa molekile buri ku murongo uri hagati ya poroteyine za ribosomal uL9 na eL30 (Ishusho ya 5a). Iyi miterere yari yarasobanuwe mbere mu miterere ya Saccharomyces cerevisiae ribosome nk'ahantu ho gufatanya na nucleotide ya 25S ya rRNA A3186 (igice cy'inyongera ya ES39L rRNA)38. Byagaragaye ko muri ribosome za P. locustae ES39L zangiritse, iyi miterere ihuza nucleotide imwe itazwi 31, kandi bifatwa ko iyi nucleotide ari ubwoko bwa nyuma bwa rRNA bugabanutse, aho uburebure bwa rRNA ari ~130-230 bases. ES39L igabanutseho nucleotide imwe 32.43. Amashusho yacu ya cryo-EM ashyigikira igitekerezo cy'uko ubucucike bushobora gusobanurwa na nucleotide. Ariko, imiterere yacu yo hejuru yagaragaje ko iyi nucleotide ari molekile ya extraribosomal, wenda AMP (Ishusho ya 5a, b).
Hanyuma twabajije niba aho urusobe rw'uturemangingo rwagaragaraga muri ribosome ya E. cuniculi cyangwa niba hari harabayeho mbere. Kubera ko urusobe rw'uturemangingo rushingiye ahanini ku bisigazwa bya Phe170 na Lys172 muri poroteyine ya eL30 ribosomal, twasuzumye uburyo ibisigazwa by'uturemangingo byabungabunzwe muri eukaryotes 4396 zihagarariye. Nkuko byagenze kuri uL15 yavuzwe haruguru, twasanze ibisigazwa bya Phe170 na Lys172 bibitswe cyane muri Microsporidia isanzwe, ariko ntibiboneka mu zindi eukaryotes, harimo na Microsporidia Mitosporidium na Amphiamblys zitasanzwe, aho igice cya ES39L rRNA kitagabanutseho 44, 45, 46 (Ishusho ya 5c). -e).
Iyi mibare ihuriweho, ishyigikira igitekerezo cy'uko E. cuniculi hamwe n'izindi microsporidia za canonical byahinduye ubushobozi bwo gufata neza umubare munini wa metabolites nto mu miterere ya ribosome kugira ngo bibe icyitegererezo cy'igabanuka ry'urugero rwa rRNA na poroteyine. Mu kubikora, bagize ubushobozi budasanzwe bwo gufata nucleotides hanze ya ribosome, bigaragaza ko imiterere ya molekile ikora icyitegererezo ifata metabolites nto nyinshi kandi ikazikoresha nk'imiterere y'uduce twa RNA na poroteyine twangiritse.
Igice cya gatatu kitari cyarateguwe cy’ikarita yacu ya cryo-EM, kiboneka mu gice kinini cya ribosomal. Ubushobozi bwo hejuru (2.6 Å) bw’ikarita yacu bugaragaza ko ubu bucucike ari ubw’amaporoteyine afite uruvange rwihariye rw’ibisigazwa binini by’uruhererekane rw’impande, byatumye dushobora kumenya ubu bucucike nk’poroteyine ya ribosomal itari izwi mbere twabonye yitwaga msL2 (poroteyine yihariye ya Microsporidia L2) (uburyo, ishusho ya 6). Ubushakashatsi bwacu bwa homoloji bwagaragaje ko msL2 ibitswe mu bwoko bwa Microsporidia bwa Encephaliter na Orosporidium, ariko ikaba idahari mu bundi bwoko, harimo n’ubundi bwoko bwa Microsporidia. Mu miterere ya ribosomal, msL2 ifata icyuho giterwa no gutakaza ES31L rRNA yagutse. Muri iki cyuho, msL2 ifasha gutuza rRNA kandi ishobora kwishyura igihombo cya ES31L (Ishusho ya 6).
Ubucucike bwa electron n'icyitegererezo cya poroteyine ya ribosomal ya Microsporidia-specific msL2 iboneka muri E. cuniculi ribosomes. b Ribosome nyinshi za eukaryotic, harimo na 80S ribosome ya Saccharomyces cerevisiae, zifite ES19L rRNA amplification yatakaye mu moko menshi ya Microsporidian. Imiterere ya V. necatrix microsporidia ribosome yari yashyizweho mbere igaragaza ko kubura kwa ES19L muri izi parasite bisubizwa n'ihindagurika rya poroteyine nshya ya msL1 ribosomal. Muri ubu bushakashatsi, twasanze E. cuniculi ribosome yanakoze poroteyine ya ribosomal RNA nk'indishyi igaragara ku kubura kwa ES19L. Ariko, msL2 (ubu ivugwa nka poroteyine ya ECU06_1135) na msL1 bifite inkomoko zitandukanye mu miterere no mu iterambere. c Ubu buvumbuzi bw'ivuka rya poroteyine za ribosomal za msL1 na msL2 zidafite aho zihuriye n'ihindagurika ry'ibinyabuzima, bugaragaza ko niba ribosomes zunze ubumwe mu miterere yazo ya rRNA, zishobora kugera ku rwego rudasanzwe rw'ubusumbane bw'ibice ndetse no mu bwoko buto bw'ibinyabuzima bifitanye isano rya hafi. Ubu buvumbuzi bushobora gufasha gusobanura inkomoko n'ihindagurika rya ribosome ya mitochondrial, izwiho kugabanuka cyane kwa rRNA no guhindagurika kudasanzwe mu miterere ya poroteyine mu moko yose.
Hanyuma twagereranije poroteyine ya msL2 na poroteyine ya msL1 yavuzwe mbere, poroteyine yonyine izwi ya ribosomal ya microsporidia iboneka muri ribosome ya V. necatrix. Twashakaga gusuzuma niba msL1 na msL2 bifitanye isano mu buryo bw’ubwihindurize. Isesengura ryacu ryagaragaje ko msL1 na msL2 bifite umwobo umwe mu miterere ya ribosomal, ariko bifite imiterere itandukanye y’ibanze n’iya gatatu, bigaragaza inkomoko yazo yigenga y’ubwihindurize (Ishusho ya 6). Bityo, kuvumbura kwacu msL2 gutanga ibimenyetso byerekana ko amatsinda y’ubwoko buto bwa eukaryotic bushobora guhindura poroteyine za ribosomal zitandukanye mu buryo bwihariye kugira ngo byishyure igihombo cy’uduce twa rRNA. Iki kimenyetso kiragaragara kuko ribosome nyinshi za eukaryotic za cytoplasmic zirimo poroteyine idahinduka, harimo n’umuryango umwe wa poroteyine 81 za ribosomal. Kugaragara kwa msL1 na msL2 mu byiciro bitandukanye bya microsporidia bitewe no gutakaza ibice bya rRNA byagutse bigaragaza ko kwangirika kw’imiterere ya molekile y’udukoko bituma udukoko dushaka impinduka zisimbura izindi, amaherezo zishobora gutuma tuboneka mu miterere itandukanye y’udukoko.
Amaherezo, ubwo icyitegererezo cyacu cyarangiraga, twagereranije imiterere ya ribosome ya E. cuniculi n'ibyari byarahanuwe muri uruhererekane rwa genome. Poroteyine nyinshi za ribosomal, zirimo eL14, eL38, eL41, na eS30, mbere byakekwaga ko zitaboneka muri genome ya E. cuniculi bitewe nuko hagaragaraga ko nta homologues zazo muri genome ya E. cuniculi. Gutakaza poroteyine nyinshi za ribosomal nabyo biravugwa mu zindi parasites nyinshi zo mu ngirabuzima fatizo zagabanutse cyane hamwe n'uturemangingo tw'umubiri. Urugero, nubwo bagiteri nyinshi zibaho zifite umuryango umwe wa poroteyine 54 za ribosomal, 11 gusa muri izi poroteyine ni zo zifite homologues zishobora kugaragara muri buri genome yasesenguwe ya bagiteri zibujijwe. Mu gushyigikira iki gitekerezo, gutakaza poroteyine za ribosomal byagaragaye mu bushakashatsi muri V. necatrix na P. locuptae microsporidia, zidafite poroteyine za eL38 na eL4131,32.
Ariko, imiterere yacu igaragaza ko eL38, eL41, na eS30 gusa ari byo byatakaye muri ribosome ya E. cuniculi. Poroteyine ya eL14 yarazigamwe kandi imiterere yacu yagaragaje impamvu iyi poroteyine itaboneka mu bushakashatsi bwa homology (Ishusho ya 7). Muri ribosome ya E. cuniculi, ahantu henshi ho gufatana kwa eL14 haratakaye bitewe no kwangirika kwa ES39L ya rRNA-amplified. Mu gihe ES39L itariho, eL14 yatakaje igice kinini cy’imiterere yayo ya kabiri, kandi 18% gusa by’uruhererekane rwa eL14 byari bimwe muri E. cuniculi na S. cerevisiae. Uku kubungabungwa nabi kw’uruhererekane ni ikintu gitangaje kuko na Saccharomyces cerevisiae na Homo sapiens - ibinyabuzima byahindutse imyaka miliyari 1.5 bitandukanye - bisangiye ibirenga 51% by’ibisigazwa bimwe muri eL14. Uku gutakaza uburyo budasanzwe bwo kubungabunga ibidukikije bisobanura impamvu E. cuniculi eL14 ubu ivugwaho kuba poroteyine ya M970_061160 aho kuba poroteyine ya ribosomal ya eL1427.
na Microsporidia ribosome yatakaje ES39L rRNA yongerewe, byatumye igice cy’aho poroteyine ya eL14 ribosomal ihurira. Iyo ES39L idafite, poroteyine ya eL14 mikorobe itakaza imiterere yayo ya kabiri, aho α-helix yahoze ihuza rRNA ihinduka uburebure buke. b Guhuza imiterere myinshi bigaragaza ko poroteyine ya eL14 ibungabungwa cyane mu bwoko bwa eukaryotic (57% by’imiterere y’uruhererekane hagati y’umusemburo n’uturemangingo tw’abantu), ariko ikaba idakungahaye kandi itandukanye muri microsporidia (aho nta bisigazwa birenga 24% bisa n’uturemangingo twa eL14). Kuva kuri S. cerevisiae cyangwa H. sapiens). Uku kubungabunga imiterere y’uruhererekane no guhinduka kw’imiterere y’uruhererekane bisobanura impamvu imiterere y’uruhererekane ya eL14 itigeze iboneka muri E. cuniculi n’impamvu iyi poroteyine ikekwa ko yatakaye muri E. cuniculi. Mu buryo bunyuranye, E. cuniculi eL14 yari yaravuzwe mbere nka poroteyine ya M970_061160. Iyi ngingo igaragaza ko ubwoko butandukanye bwa genome ya microsporidia muri iki gihe bukabije: jeni zimwe na zimwe zikekwaho kuba zarabuze muri microsporidia mu by'ukuri zirabikwa, nubwo mu buryo butandukanye cyane; ahubwo, zimwe zikekwaho kuba zikora jeni za microsporidia ku poroteyine zihariye ku nyoni (urugero, poroteyine yiyumvirwaho ya M970_061160) mu by'ukuri zikora poroteyine zitandukanye cyane ziboneka mu zindi eukaryotes.
Iki cyegeranyo cyerekana ko rRNA denaturation ishobora gutuma habaho gutakaza gukomeye kwa sequence mu miterere ya poroteyine za ribosomal zegeranye, bigatuma izi poroteyine zitaboneka mu bushakashatsi bwa homology. Bityo, dushobora kurenza urugero rw'igabanuka rya molekile mu tunyangingo duto twa genome, kubera ko poroteyine zimwe na zimwe zikekwaho kubura zikomeza kubaho, nubwo zahindutse cyane.
Ni gute udukoko dushobora kugumana imikorere y’imashini zatwo zikora mu gihe cy’igabanuka rikomeye rya genome? Ubushakashatsi bwacu busubiza iki kibazo busobanura imiterere y’urusobe rwa molekile (ribosome) rwa E. cuniculi, ikiremwa gifite imwe muri genome ntoya za eukaryotike.
Bimaze imyaka hafi makumyabiri bizwi ko poroteyine na RNA mu dukoko duto duto akenshi bitandukanye na molecules zazo zimeze nk'iz'ubwoko busanzwe kuko zidafite aho zigenzura ubuziranenge, zigabanuka zikagera kuri 50% by'ingano yazo mu dukoko duto duto, nibindi. Impinduka nyinshi zica intege zibangamira ihindagurika n'imikorere. Urugero, ribosomes z'uturemangingo duto twa genome, harimo udukoko twinshi two mu ngirabuzima fatizo n'uturemangingo tw'umubiri, byitezwe ko zitagira poroteyine nyinshi za ribosomal ndetse na kimwe cya gatatu cya nucleotides za rRNA ugereranije n'ubwoko busanzwe buzwi nka 27, 29, 30, 49. Ariko, uburyo izi molekyuli zikora mu dukoko buracyari amayobera, byigwa cyane cyane binyuze mu bushakashatsi bugereranya genome.
Ubushakashatsi bwacu bwerekana ko imiterere ya macromolecules ishobora kugaragaza ibintu byinshi by’ubwihindurize bigoye kubikura mu bushakashatsi busanzwe bwa genomike ku dukoko two mu ngirabuzima fatizo n’ibindi binyabuzima bidashobora kwitabwaho (Ishusho y’inyongera ya 7). Urugero, urugero rwa poroteyine ya eL14 rugaragaza ko dushobora kurenza urugero rw’uko ibikoresho bya molekile byangiritse mu bwoko bwa parasites. Parasites zo mu bwoko bwa Encephalitic ubu bikekwa ko zifite amagana ya mikorosporidia. Ariko, ibisubizo byacu bigaragaza ko zimwe muri izi jeni zisa n’izihariye mu by’ukuri ari ubwoko butandukanye cyane bwa jeni busanzwe mu zindi eukaryotes. Byongeye kandi, urugero rwa poroteyine ya msL2 rugaragaza uburyo twirengagiza poroteyine nshya za ribosomal kandi tugasuzugura ingano y’imashini za molekile za parasites. Urugero rwa molekile nto rugaragaza uburyo dushobora kwirengagiza udushya twinshi mu miterere ya molekile za parasites zishobora kuziha imikorere mishya ya biyoloji.
Ibyo bisubizo byose hamwe bidufasha gusobanukirwa itandukaniro riri hagati y’imiterere ya molekile y’ibinyabuzima bidafite aho bibogamiye n’ibindi binyabuzima bifite ubuzima busanzwe. Tugaragaza ko imashini za molekile, zitekerezwaho ko zagabanutse, zigenda zihinduka, kandi zigahinduka mu buryo butandukanye, ahubwo zifite imiterere idasanzwe yirengagijwe mu buryo busanzwe.
Ku rundi ruhande, uduce twa rRNA tutari twinshi hamwe n'uduce twahujwe twasanze muri ribosomes za E. cuniculi bigaragaza ko kugabanuka kwa genome bishobora guhindura ndetse n'ibice by'imashini y'ibanze ya molekile ibitswe mu nzego eshatu z'ubuzima - nyuma y'imyaka hafi miliyari 3.5. ubwihindurize bw'ibinyabuzima bwigenga.
Uduce twa rRNA tudafite ububyimbirwe kandi twahujwe muri ribosome za E. cuniculi dushishikajwe cyane n’ubushakashatsi bwakozwe mbere ku ngirabuzimafatizo za RNA muri bagiteri zifata imiyoboro y’amaraso. Urugero, muri aphid endosymbiont Buchnera aphidicola, ngirabuzimafatizo za rRNA na tRNA byagaragaye ko zifite imiterere iterwa n’ubushyuhe bitewe n’imiterere ya A+T ndetse n’igice kinini cya pairs zidafite ubuziranenge20,50. Izi mpinduka muri RNA, kimwe n’impinduka muri ngirabuzimafatizo za poroteyine, ubu bifatwa nk’impamvu ituma ngirabuzimafatizo zifatana cyane n’abafatanyabikorwa ndetse no kudashobora kwa ngirabuzimafatizo kohereza ubushyuhe21, 23. Nubwo ngirabuzimafatizo za microsporidia rRNA zifite impinduka zitandukanye mu miterere, imiterere y’izi mpinduka igaragaza ko kugabanuka k’ubushyuhe no kwishingikiriza cyane kuri poroteyine za chaperone bishobora kuba ari ibintu bisanzwe ku ngirabuzimafatizo za RNA mu binyabuzima bifite genome yagabanutse.
Ku rundi ruhande, imiterere yacu igaragaza ko parasite microsporidia yahinduye ubushobozi bwihariye bwo kurwanya ibice bya rRNA na poroteyine byabitswe mu buryo bwagutse, iteza imbere ubushobozi bwo gukoresha metabolite nto nyinshi kandi ziboneka byoroshye nk'imiterere isa n'ibice bya rRNA na poroteyine byangiritse. Kwangirika kw'imiterere ya molekile. Iki gitekerezo gishyigikiwe n'uko molekile nto zishyura igihombo cy'ibice bya poroteyine muri rRNA na ribosome za E. cuniculi zifatana n'ibisigazwa byihariye bya mikorosporidia muri poroteyine uL15 na eL30. Ibi bigaragaza ko gufatana kwa molekile nto na ribosome bishobora kuba umusaruro w'uburyo bwiza bwo guhitamo, aho impinduka zihariye za mikorosporidia muri poroteyine za ribosome zatoranijwe kubera ubushobozi bwazo bwo kongera ubufatanye bwa ribosome kuri molekile nto, bishobora gutuma habaho ibinyabuzima bya ribosomal bikora neza. Ubuvumbuzi bugaragaza udushya twinshi mu miterere ya molekile ya mikorobe kandi buduha gusobanukirwa neza uburyo imiterere ya molekile ya mikorobe ikomeza gukora nubwo hari impinduka zigabanuka.
Kugeza ubu, kumenya izi molekile nto ntibirasobanuka neza. Ntibirasobanuka neza impamvu izi molekile nto mu miterere ya ribosomal zitandukaniye ku bwoko bwa microsporidia. By'umwihariko, ntibirasobanuka neza impamvu imiterere ya nucleotide igaragara muri ribosome za E. cuniculi na P. locustae, kandi ntabwo igaragara muri ribosome za V. necatrix, nubwo hari ibisigazwa bya F170 muri poroteyine ya eL20 na K172 ya V. necatrix. Uku gusiba bishobora guterwa n'ibisigazwa 43 uL6 (biherereye hafi y'umufuka w'ibisigazwa bya nucleotide), ari byo tyrosine muri V. necatrix atari threonine muri E. cuniculi na P. locustae. Uruhererekane rw'uruhande runini rwa aromatike rwa Tyr43 rushobora kubangamira imiterere ya nucleotide bitewe n'aho steric ihurira. Ubundi buryo, gusiba kwa nucleotide bigaragara bishobora guterwa no kuba hari ubushobozi buke bwo gufata amashusho ya cryo-EM, bigatuma ibice bya ribosomal bya V. necatrix bitagaragara.
Ku rundi ruhande, akazi kacu kagaragaza ko inzira yo kwangirika kwa genome ishobora kuba imbaraga y’ubuhanga. By’umwihariko, imiterere ya E. cuniculi ribosome igaragaza ko kubura kwa rRNA na poroteyine mu mikorosporidia ribosome bitera umuvuduko w’ihindagurika ry’imiterere y’ibinyabuzima, bigatuma habaho impinduka mu miterere ya ribosome. Izi tandukaniro ziba kure y’aho ribosome ikorera kandi zisa nkaho zifasha mu kubungabunga (cyangwa kugarura) ihuriro ryiza rya ribosome ryashoboraga guhungabana bitewe no kugabanuka kwa rRNA. Ibi bigaragaza ko udushya dukomeye twa mikorosporidia ribosome gisa nkaho twahindutse tukaba ari ngombwa ko habaho uburyo bwo gukumira imihindagurikire y’uturemangingo.
Ahari ibi bigaragazwa neza n’uburyo nucleus ihambira, bitarigeze bigaragara mu bindi binyabuzima kugeza ubu. Kuba ibisigazwa by’udusimba twa nucleus bihambira biri muri microsporidia isanzwe, ariko bitari mu zindi eukaryotes, bigaragaza ko ahantu nucleus ihambira atari ibisigazwa gusa bitegereje kuzimira, cyangwa ahantu ha nyuma rRNA igomba kugaruka ku ishusho ya nucleus imwe imwe. Ahubwo, uru rubuga rusa n’aho ari ikintu cy’ingirakamaro cyashoboraga kuba cyarahindutse mu bihe byinshi byo guhitamo neza. Ahantu nucleus ihambira hashobora kuba ari umusaruro w’uburyo karemano bwo guhitamo: iyo ES39L imaze kwangirika, microsporidia ihatirwa gushaka indishyi kugira ngo igarure uburyo bwiza bwo guhindura imiterere ya ribosomu mu gihe ES39L idafite. Kubera ko iyi nucleotide ishobora kwigana uburyo molekile ya A3186 nucleotide muri ES39L, molekile ya nucleotide iba inkingi y’ubwubatsi bwa ribosomu, uburyo bwo kuyihambira burushaho kunozwa no guhinduka kw’uruhererekane rwa eL30.
Ku bijyanye n'ihindagurika rya molekile mu miterere y'udukoko two mu ngirabuzimafatizo, ubushakashatsi bwacu bwerekana ko imbaraga zo guhitamo karemano kwa Darwin n'ihindagurika rya genome mu kubora bidakora icyarimwe, ahubwo bihindagurika. Ubwa mbere, ihindagurika rya genome rikuraho ibintu by'ingenzi bya biomolecules, bigatuma inyishyu iba ikenewe cyane. Iyo parasite zujuje iki cyifuzo binyuze mu guhitamo karemano kwa Darwins, ni bwo macromolecules zabo zizagira amahirwe yo guteza imbere imiterere yazo itangaje kandi igezweho. Icy'ingenzi ni uko ihindagurika ry'ahantu hahurira nucleotide muri ribosome ya E. cuniculi rigaragaza ko iyi miterere y'ihindagurika rya molekile idatuma gusa impinduka mbi zibaho, ahubwo rimwe na rimwe igatanga imikorere mishya ku macromolecules ya parasites.
Iki gitekerezo gihuye n’inyigisho ya Sewell Wright ivuga ku kuringaniza ibintu, ivuga ko uburyo buhamye bwo guhitamo ibintu karemano bugabanya ubushobozi bw’ibinyabuzima bwo guhanga udushya51,52,53. Ariko, niba imiterere y’uturemangingo ibangamiye uburyo ibintu bisanzwe bitoranywa, ubwo buryo bushobora kuzana impinduka zitari zo ubwazo zihinduka (cyangwa se zikagira ingaruka mbi) ahubwo zigatera izindi mpinduka zitanga ubuzima bwiza cyangwa ibikorwa bishya by’ibinyabuzima. Urwego rwacu rushyigikira iki gitekerezo rugaragaza ko ubwoko bumwe bw’impinduka bugabanya imikorere n’imikorere ya biomolecule busa n’aho ari bwo buba imbarutso nyamukuru yo kunoza imikorere yayo. Dukurikije icyitegererezo cy’impinduka ku mpande zombi, ubushakashatsi bwacu bwerekana ko kwangirika kwa genome, ubusanzwe ifatwa nk’inzira yo kwangirika, na byo ari ikintu gikomeye gitera udushya, rimwe na rimwe ndetse wenda akenshi bigatuma macromolecules zigira ibikorwa bishya bya parasites. zishobora kubikoresha.