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Ubwihindurize bwa parasite ya mikorobe ikubiyemo guhangana hagati yo gutoranya kamere, itera parasite gutera imbere, hamwe na drift genetique, itera parasite gutakaza genes no kwegeranya ihinduka ryimiterere.Hano, kugirango twumve uburyo uku guhangana kugaragara ku gipimo cya macromolecule imwe, turasobanura imiterere ya cryo-EM ya ribosome ya Encephalitozoon cuniculi, ibinyabuzima bya eukaryotic bifite imwe muri genome ntoya muri kamere.Kugabanuka gukabije kwa rRNA muri E. cuniculi ribosomes iherekejwe nimpinduka zubatswe zitigeze zibaho, nkubwihindurize bwabashinzwe kumenyekanisha rRNA mbere na rRNA bitamenyekanye.Byongeye kandi, E. cuniculi ribosome yarokotse gutakaza ibice bya rRNA na proteyine biteza imbere ubushobozi bwo gukoresha molekile ntoya nkigana imiterere yimiterere ya rRNA yangiritse na proteyine.Muri rusange, twerekana ko imiterere ya molekile yatekerejweho kugabanuka, kwangirika, no guhindagurika kwimiterere ihindagurika ifite uburyo bwinshi bwo kwishyura indishyi zituma zikora nubwo zigenda ziyongera cyane.
Kuberako amatsinda menshi ya parasite ya mikorobe afite ibikoresho byihariye bya molekuline kugirango akoreshe abayakiriye, akenshi tugomba guteza imbere imiti itandukanye kumatsinda atandukanye ya parasite1,2.Nyamara, ibimenyetso bishya byerekana ko ibintu bimwe na bimwe byerekana ubwihindurize bwa parasite bihujwe kandi ahanini bikaba byateganijwe, byerekana ko hashobora kubaho uburyo bwo kuvura bwagutse muri mikorobe 3.4,5,6,7,8,9.
Ibikorwa byabanje byagaragaje icyerekezo rusange cyubwihindurize muri parasite ya mikorobe bita kugabanya genome cyangwa kwangirika kwa gen10,11,12,13.Ubushakashatsi bugezweho bwerekana ko iyo mikorobe iretse ubuzima bwabo bwisanzuye kandi igahinduka parasite idasanzwe (cyangwa endosymbionts), genome zabo zigenda buhoro ariko butangaje metamorphose mumyaka miriyoni 9,11.Mubikorwa bizwi kwangirika kwa genome, parasite ya mikorobe ikusanya ihinduka ryimiterere ihindura genes nyinshi zingenzi zahindutse pseudogene, bigatuma habaho gutakaza buhoro buhoro no guhinduka kwa mutation14,15.Uku gusenyuka kurashobora gusenya kugeza kuri 95% ya gen mu binyabuzima bya kera cyane mu mitsi ugereranije n’ibinyabuzima bifitanye isano rya bugufi.Rero, ubwihindurize bwa parasite idasanzwe ni ugukurura intambara hagati yimbaraga ebyiri zihanganye: Guhitamo kamere ya Darwin, biganisha ku kunoza parasite, no gusenyuka kwa genome, guta parasite mu kwibagirwa.Uburyo parasite yashoboye kuva muri iyi ntambara yo kurwana no kugumana ibikorwa byimiterere ya molekile yayo ntibisobanutse neza.
Nubwo uburyo bwo kwangirika kwa genome butarasobanuka neza, bigaragara ko bibaho ahanini bitewe nubwoko bukunze kugenda.Kubera ko parasite iba mubantu bake, badahuje igitsina, kandi bafite genetike nkeya, ntibashobora gukuraho neza ihinduka ryimiterere ihinduka rimwe na rimwe riba mugihe cyo kwigana ADN.Ibi biganisha ku kwegeranya bidasubirwaho ihindagurika ryangiza no kugabanya genoside ya parasite.Nkigisubizo, parasite ntabwo itakaza genes gusa itagikenewe kugirango ibeho mubidukikije.Nubushobozi bwabaturage ba parasite kurandura burundu ihinduka ryimiterere ihindagurika rimwe na rimwe ritera ihinduka ryimiterere ya genome yose, harimo na genes zabo zikomeye.
Ibyinshi mubyo dusobanukiwe no kugabanya genome bishingiye gusa kubigereranya nurwego rwa genome, tutitaye cyane kumihindagurikire ya molekile nyayo ikora imirimo yo murugo kandi ikaba ishobora kwibasirwa nibiyobyabwenge.Ubushakashatsi bugereranije bwerekanye ko umutwaro w’imiterere ihindagurika ya mikorobe yo mu bwoko bwa mikorobe isa nkaho iteganya poroteyine na acide nucleic acide kugirango zidahinduka kandi zegeranye, bigatuma barushaho kuba chaperone kandi bakumva ubushyuhe bukabije 19,20,21,22,23.Byongeye kandi, parasite zitandukanye-ubwihindurize bwigenga rimwe na rimwe butandukanijwe n’imyaka igera kuri miliyari 2,5 - byagize igihombo gisa n’ibigo bishinzwe kugenzura ubuziranenge muri sintezamubiri ya poroteyine5,6 hamwe n’uburyo bwo gusana ADN24.Nyamara, bike bizwi ku ngaruka zubuzima bwimitsi itagaragara ku zindi miterere yose ya macromolecules, harimo no guhuza molekile n'umutwaro ugenda wiyongera ku ihinduka ry’imiterere ihindagurika.
Muri iki gikorwa, kugirango dusobanukirwe neza ubwihindurize bwa poroteyine na acide nucleic acide ya mikorobe idasanzwe, twagennye imiterere ya ribosomes ya parasite yo mu nda ya Encephalitozoon cuniculi.EVuba aha, imiterere ya cryo-EM ribosome yagenwe kuri genoside yagabanutse ku buryo bugaragara bwa Microsporidia, Paranosema locustae, na Vairimorpha necatrix31,32 (~ 3.2 Mb genome).Izi nzego zerekana ko igihombo cya rRNA cyongerewe imbaraga cyatewe niterambere ryimikoranire mishya hagati ya poroteyine zituranye na ribosomal cyangwa kubona poroteyine nshya za msL131,32.Ubwoko bwa Encephalitozoon (genome ~ miliyoni 2,5 bp), hamwe na mwene wabo wa hafi Ordospora, berekana urugero ruhebuje rwo kugabanya genome muri eukaryote - bafite genes zitarenga 2000 za code-coding, kandi biteganijwe ko ribosomes zabo zitabura gusa ibice byo kwaguka kwa rRNA (ibice bya rRNA bitandukanya na ribosome ya ribosome na selile ya ribosome). 27,28.Kubwibyo, twanzuye ko E. cuniculi ribosome ishobora kwerekana ingamba zitazwi mbere yo guhuza molekile no kwangirika kwa genome.
Imiterere yacu ya cryo-EM yerekana ntoya ya eukaryotic cytoplasmic ribosome igomba kurangwa kandi ikanatanga ubushishozi bwukuntu urwego ruhebuje rwo kugabanya genome rugira ingaruka kumiterere, guterana, no kwihindagurika kwimashini ya molekile ihuriweho ningirabuzimafatizo.Twabonye ko E. cuniculi ribosome irenga ku mahame menshi yabitswe cyane yo kuzunguruka kwa RNA no guterana kwa ribosome, maze tuvumbura poroteyine nshya, mbere itazwi.Mu buryo butunguranye, twerekana ko microsporidia ribosomes yahinduye ubushobozi bwo guhuza molekile nto, kandi tugavuga ko kugabanuka muri rRNA na proteyine bitera udushya twihinduramatwara bishobora gutanga imico y'ingirakamaro kuri ribosome.
Kugira ngo turusheho gusobanukirwa ubwihindurize bwa poroteyine na acide nucleique mu binyabuzima byo mu nda, twahisemo gutandukanya intanga za E. cuniculi n’imico y’uturemangingo tw’inyamabere zanduye kugira ngo dusukure ribosome kandi tumenye imiterere ya ribosomes.Biragoye kubona umubare munini wa microsporidia ya parasitike kuko microsporidia idashobora guhingwa muburyo bwintungamubiri.Ahubwo, bakura kandi bakororoka gusa imbere muri selile.Kubwibyo, kugirango tubone biomass ya E. cuniculi kugirango isukure ribosome, twanduye umurongo wimpyiko zinyamabere RK13 hamwe na spore E. cuniculi hanyuma duhindura ingirabuzimafatizo zanduye ibyumweru byinshi kugirango E. cuniculi ikure kandi igwire.Twifashishije monolayeri yanduye ya kimwe cya kabiri cya metero kare, twashoboye kweza mg 300 za sporore ya Microsporidia hanyuma tuyikoresha mugutandukanya ribosomes.Twahise duhagarika spore isukuye hamwe namasaro yikirahure hanyuma dutandukanya ribosomes itavanze dukoresheje intambwe ya polyethylene glycol igabanya igice cya lysates.Ibi byadushoboje kubona hafi 300 µg mbisi E. cuniculi ribosomes yo gusesengura imiterere.
Twahise dukusanya amashusho ya cryo-EM dukoresheje ingero za ribosome zavuyemo hanyuma dutunganya aya mashusho dukoresheje masike ihuye na subunit nini ya ribosomal, umutwe muto wa subunit, na subunit nto.Muri iki gikorwa, twakusanyije amashusho yingingo zigera ku 108.000 za ribosomal hanyuma tubara amashusho ya cryo-EM ifite ibyemezo bya 2.7 Å (Ishusho yinyongera 1-3).Twahise dukoresha amashusho ya cryoEM kugirango twerekane rRNA, proteine ​​ya ribosomal, hamwe na hibernation Mdf1 ifitanye isano na E. cuniculi ribosomes (Ishusho 1a, b).
Imiterere ya E. cuniculi ribosome muburyo bugoye hamwe na hibernation Mdf1 (pdb id 7QEP).b Ikarita yo gusinzira Mdf1 ifitanye isano na E. cuniculi ribosome.c Ikarita yuburyo bwa kabiri ugereranije rRNA yagaruwe mubwoko bwa Microsporidian nuburyo buzwi bwa ribosomal.Ikibaho cyerekana aho ibice bya rRNA byongerewe imbaraga (ES) hamwe na site ikora ya ribosome, harimo urubuga rwa decoding (DC), sarcinicin loop (SRL), hamwe na transfert ya peptidyl (PTC).d Ubucucike bwa electron bujyanye na peptidyl transfert ya centre ya E. cuniculi ribosome yerekana ko iyi site ya catalitiki ifite imiterere imwe muri parasite ya E. cuniculi nabayakira, harimo na H. sapiens.e, f Ubucucike bwa elegitoronike bujyanye na decoding center (e) hamwe nuburyo bwimiterere yikigo cya decoding (f) byerekana ko E. cuniculi ifite ibisigisigi U1491 aho kuba A1491 (nomero ya E. coli) mubindi byinshi bya eukaryote.Ihinduka ryerekana ko E. cuniculi ashobora kuba yumva antibiyotike yibasira uru rubuga rukora.
Bitandukanye nuburyo bwashizweho mbere bwa V. necatrix na P. locustae ribosomes (izo nyubako zombi zerekana umuryango umwe wa microsporidia Nosematidae kandi zirasa cyane), 31.32 E. cuniculi ribosomes ikora inzira nyinshi za rRNA no gucamo poroteyine.Ibindi gutandukana (Ishusho yinyongera 4-6).Muri rRNA, impinduka zigaragara cyane harimo gutakaza burundu igice cya 25S rRNA cyongerewe igice cya ES12L no kwangirika igice cya h39, h41, na H18 (Ishusho 1c, Ishusho yinyongera 4).Muri poroteyine za ribosomal, impinduka zagaragaye cyane harimo gutakaza burundu poroteyine ya eS30 no kugabanya eL8, eL13, eL18, eL22, eL29, eL40, uS3, uS9, uS14, uS17, na poroteyine eS7 (Ishusho yinyongera 4, 5).
Rero, igabanuka rikabije rya genome yubwoko bwa Encephalotozoon / Ordospora bigaragarira mu miterere yabyo ya ribosome: E. cuniculi ribosomes ihura no gutakaza cyane ibintu bya poroteyine muri eukaryotic cytoplasmic ribosomes bitewe n’imiterere, kandi nta nubwo bifite ibice bya rRNA hamwe na poroteyine bibitswe cyane muri domeni eshatu gusa.Imiterere ya E. cuniculi ribosome itanga urugero rwa molekile ya mbere kuri izi mpinduka kandi ikagaragaza ibintu byabayeho biturutse ku bwihindurize bwirengagijwe na genomics igereranya ndetse n’ubushakashatsi bw’imiterere y’imiterere y’imiterere y’imitsi (Ishusho yinyongera 7).Hasi, turasobanura buri kimwe mubyabaye hamwe ninkomoko yabyo byabayeho biturutse ku bwihindurize n'ingaruka zishobora kugira ku mikorere ya ribosome.
Twahise dusanga ko, usibye ibice binini bya rRNA, E. cuniculi ribosomes ifite itandukaniro rya rRNA kurubuga rumwe rukora.Nubwo peptidyl transfert ya centre ya E. cuniculi ribosome ifite imiterere nkiyindi ribosomes ya eukaryotic (Igishusho 1d), ikigo cya decoding kiratandukanye bitewe nuburyo bukurikiranye kuri nucleotide 1491 (E. coli nimero, Ishusho 1e, f).Uku kwitegereza ni ngombwa kuko urubuga rwa decoding ya eukaryotic ribosomes mubusanzwe rurimo ibisigazwa G1408 na A1491 ugereranije nibisigazwa byubwoko bwa bagiteri A1408 na G1491.Iri tandukaniro rishingiye ku myumvire itandukanye ya bagiteri na eukaryotic ribosomes ku muryango wa aminoglycoside ya antibiyotike ya ribosomal na molekile ntoya yibasira urubuga.Kurubuga rwa decoding ya E. cuniculi ribosome, ibisigisigi A1491 byasimbuwe na U1491, birashoboka ko hashyirwaho interineti idasanzwe ihuza molekile nto yibasiye uru rubuga rukora.Ubwoko bumwe bwa A14901 buraboneka no mu zindi microsporidia nka P. locustae na V. necatrix, byerekana ko ikwirakwizwa mu bwoko bwa microsporidia (Ishusho 1f).
Kubera ko urugero rwa E. cuniculi ribosome rwatandukanijwe na spore idakora, twagerageje ikarita ya cryo-EM ya E. cuniculi kugirango tubone ibisobanuro bya ribosome mbere yo guhangayika cyangwa inzara.Impamvu zo gusinzira 31,32,36,37, 38. Twahujije imiterere yashizweho mbere yo gusinzira ribosome hamwe nikarita ya cryo-EM ya E. cuniculi ribosome.Kuri docking, S. cerevisiae ribosomes yakoreshwaga muburyo bukomeye hamwe na hibernation Stm138, inzige za nzige zinzitane hamwe na Lso232, hamwe na V. necatrix ribosomes murwego hamwe na Mdf1 na Mdf231.Mugihe kimwe, twasanze ubwinshi bwa cryo-EM buhuye nibintu bisigaye Mdf1.Kimwe na Mdf1 ihuza na V. necatrix ribosome, Mdf1 nayo ihuza na E. cuniculi ribosome, aho ihagarika E site ya ribosome, birashoboka ko ifasha gutuma ribosomes iboneka mugihe sporite ya parasite idakora metabolique idakora umubiri (Ishusho 2).).
Mdf1 ihagarika E site ya ribosome, bigaragara ko ifasha kudakora ribosome mugihe sporite ya parasite idakora metabolically idakora.Mu miterere ya E. cuniculi ribosome, twasanze Mdf1 ikora umubano utazwi mbere na L1 ribosome, igice cya ribosome cyorohereza irekurwa rya tRNA yanduye muri ribosome mugihe cya synthesis.Iyi mibonano irerekana ko Mdf1 yitandukanije na ribosome ikoresheje uburyo bumwe na tRNA ya deacetylated, itanga ibisobanuro bishoboka byukuntu ribosome ikuraho Mdf1 kugirango yongere gukora synthesis.
Nyamara, imiterere yacu yerekanye umubano utazwi hagati ya Mdf1 n'amaguru ya L1 ribosome (igice cya ribosome gifasha kurekura tRNA yanduye muri ribosome mugihe cya synthesis).By'umwihariko, Mdf1 ikoresha imikoranire nki gice cyinkokora ya molekile ya tRNA yanduye (Ishusho 2).Iyi moderi ya molekulari itaramenyekana mbere yerekanaga ko Mdf1 yitandukanije na ribosome ikoresheje uburyo bumwe na tRNA ya deacetylated, isobanura uburyo ribosome ikuraho iki kintu cyo gusinzira kugirango yongere gukora intungamubiri za poroteyine.
Mugihe twubaka icyitegererezo cya rRNA, twasanze E. cuniculi ribosome yazinduye bidasanzwe uduce twa rRNA, twise rRNA yahujwe (Ishusho 3).Muri ribosomes igizwe nubutegetsi butatu bwubuzima, rRNA yikubye mubice aho rRNA nyinshi zishingiye kubiri shingiro no kuzunguruka hamwe cyangwa gukorana na poroteyine za ribosomal 38,39,40.Ariko, muri E. cuniculi ribosomes, rRNAs zisa nkizirenga kuri iri hame ryikubitiro muguhindura bimwe mubitekerezo byabo mukarere ka rRNA kitagaragara.
Imiterere ya H18 25S rRNA helix muri S. cerevisiae, V. necatrix, na E. cuniculi.Mubisanzwe, muri ribosomes izenguruka ubuzima butatu, iyi ihuza ikomatanya muri RNA helix irimo ibisigisigi 24 kugeza 34.Muri Microsporidia, mu buryo bunyuranye, umuhuza wa RRNA ugenda ugabanuka buhoro buhoro ugera kuri bibiri bihuza uridine bikungahaye birimo ibisigazwa 12 gusa.Ibyinshi muri ibyo bisigazwa byerekanwe kumashanyarazi.Igishushanyo cyerekana ko microsporidia ya parasitike isa nkaho inyuranyije n’amahame rusange yo kugundira rRNA, aho usanga rRNA ikunze guhuzwa n’ibindi bishingiro cyangwa bikagira uruhare mu mikoranire ya rRNA na proteyine.Muri microsporidia, uduce tumwe na tumwe twa rRNA dufata inshuro zitameze neza, aho icyahoze cyitwa rRNA helix gihinduka igice kimwe cyarambuye hafi kumurongo ugororotse.Kuba muri utwo turere bidasanzwe bituma microsporidia rRNA ihuza ibice bya rRNA ya kure ukoresheje umubare muto wibishingwe bya RNA.
Urugero ruhebuje rwiyi nzibacyuho irashobora kugaragara muri H18 25S rRNA helix (Ishusho 3).Mu moko kuva E. coli kugeza kubantu, ishingiro ryiyi rRNA helix irimo nucleotide 24-32, ikora helix idasanzwe.Mubikorwa byamenyekanye mbere bya ribosomal kuva kuri V. necatrix na P. locustae, 31.32 shingiro rya H18 helix ntizifunze igice, ariko guhuza nucleotide kubikwa.Ariko, muri E. cuniculi iki gice cya rRNA gihinduka umuhuza mugufi 228UUUGU232 na 301UUUUUUUUUU307.Bitandukanye nibice bisanzwe bya RRNA, izi nkunga zikungahaye kuri uridine ntizishira cyangwa ngo zikorane cyane na poroteyine za ribosomal.Ahubwo, bafata solvent-ifunguye kandi ifunguye byuzuye aho imirongo ya rRNA yaguwe hafi igororotse.Ihinduka rirambuye risobanura uburyo E. cuniculi ikoresha ibirindiro 12 bya RNA gusa kugirango yuzuze icyuho cya 33 Å hagati ya H16 na H18 rRNA, mugihe andi moko akenera byibuze inshuro ebyiri za rRNA kugirango yuzuze icyuho.
Rero, turashobora kwerekana ko, binyuze muburyo butagoranye imbaraga, microsporidia ya parasitike yashyizeho ingamba zo kwandura ndetse nibice bya rRNA bikomeza kubungabungwa cyane mubinyabuzima mubice bitatu byubuzima.Ikigaragara ni uko, mugukusanya ihinduka ryimiterere ihindura rRNA ihuza ibice bigufi bya poly-U, E. cuniculi irashobora gukora uduce duto twa rRNA turimo nucleotide nkeya zishoboka kugirango habeho ibice bya kure bya RRNA.Ibi bifasha gusobanura uburyo microsporidia yageze ku kugabanuka gukabije kwimiterere yabyo ya molekuline idatakaje uburinganire bwimikorere n'imikorere.
Ikindi kintu kidasanzwe kiranga E. cuniculi rRNA ni isura ya rRNA idafite umubyimba (Ishusho 4).Ibibyimba ni nucleotide idafite ibice bibiri byibanze biva muri RNA helix aho kubihisha.Ibyinshi muri rRNA bikora nkibikoresho bya molekuline, bifasha guhuza poroteyine zegeranye za ribosomal cyangwa ibindi bice bya rRNA.Bimwe mubibyimba bikora nka hinges, bituma rRNA helix ihindagurika kandi igahinduka neza kugirango synthesis proteine ​​itanga umusaruro 41.
a RRNA yerekana (S. cerevisiae nimero) ntaboneka muburyo bwa E. cuniculi ribosome, ariko igaragara mubindi byinshi eukaryote b E. coli, S. cerevisiae, H. sapiens, na E. cuniculi imbere ya ribosomes.parasite ibura byinshi mubya kera, bibitswe cyane rRNA.Uku kubyimba gutuza imiterere ya ribosome;kubwibyo, kubura kwabo muri microsporidia byerekana kugabanuka kwimitekerereze ya rRNA muri parasite ya microsporidia.Ugereranije n'ibiti bya P (L7 / L12 bikomoka muri bagiteri) byerekana ko gutakaza ibibyimba bya rRNA rimwe na rimwe bihura no kugaragara kw'ibibyimba bishya iruhande rw'ibibyimba byatakaye.H42 helix muri 23S / 28S rRNA ifite umubyimba wa kera (U1206 muri Saccharomyces cerevisiae) bivugwa ko ufite nibura imyaka miriyari 3,5 kubera kurindwa mubice bitatu byubuzima.Muri microsporidia, iki gihu kiravaho.Ariko, igituba gishya cyagaragaye kuruhande rwatakaye (A1306 muri E. cuniculi).
Igitangaje, twasanze E. cuniculi ribosomes ibura ibyinshi bya rRNA iboneka mu yandi moko, harimo ibibyimba birenga 30 byabitswe mu zindi eukaryote (Ishusho 4a).Iki gihombo gikuraho umubano mwinshi hagati ya ribosomal subunits hamwe na rRNA yegeranye, rimwe na rimwe bigatera imyenge minini muri ribosome, bigatuma E. cuniculi ribosome irushaho gukomera ugereranije na ribosome gakondo (Ishusho 4b).Ikigaragara ni uko twasanze ibyinshi muribi byanatakaye mububiko bwa V. necatrix na P. locustae ribosome bwamenyekanye mbere, bwirengagijwe nisesengura ryakozwe mbere 31,32.
Rimwe na rimwe, gutakaza ibibyimba bya rRNA biherekejwe niterambere ryibibyimba bishya kuruhande rwatakaye.Kurugero, P-stem ya ribosomal irimo ibibyimba U1208 (muri Saccharomyces cerevisiae) yarokotse kuva E. coli kugeza kubantu bityo bikaba bivugwa ko imaze imyaka miriyari 3,5.Mugihe cya poroteyine, iyi bulge ifasha P stem kwimuka hagati yugurura no gufunga kugirango ribosome ibashe gushakisha ibintu byubuhinduzi ikabigeza kurubuga rukora.Muri E. cuniculi ribosomes, uku kubyimba ntikuboneka;icyakora, kubyimbye gushya (G883) biherereye mubice bitatu gusa byibanze birashobora kugira uruhare mukugarura uburyo bwiza bwo guhinduka kwurwego rwa P (Ishusho 4c).
Amakuru yacu kuri rRNA adafite ibibyimba byerekana ko kugabanya rRNA bitagarukira gusa ku gutakaza ibintu bya rRNA hejuru ya ribosome, ariko birashobora no kuba birimo nucleus ya ribosome, bigatera inenge ya parasite yihariye idasobanuwe mu ngirabuzimafatizo zidafite ubuzima.ibinyabuzima bizima.
Nyuma yo kwerekana poroteyine za Canonical ribosomal na rRNA, twasanze ibice bisanzwe bya ribosomal bidashobora gusobanura ibice bitatu bigize ishusho ya cryo-EM.Babiri muri ibyo bice ni molekile nto mu bunini (Ishusho 5, Ishusho y'inyongera 8).Igice cya mbere gishyizwe hagati ya poroteyine ya ribosomal uL15 na eL18 mu mwanya usanzwe ufitwe na C-terminus ya eL18, igufi muri E. cuniculi.Nubwo tudashobora kumenya umwirondoro wiyi molekile, ingano nuburyo imiterere yiki kirwa cyinshi bisobanurwa neza no kuba hari molekile ya spermidine.Guhambira kuri ribosome bihagarikwa na microsporidia ihindagurika ryihariye muri poroteyine za uL15 (Asp51 na Arg56), bisa nkaho byongera isano ya ribosome kuri iyi molekile nto, kuko yemerera uL15 gupfunyika molekile ntoya muburyo bwa ribosomal.Umugereka w'inyongera 2).8, amakuru yinyongera 1, 2).
Amashusho ya Cryo-EM yerekana ko hariho nucleotide hanze ya ribose ihujwe na E. cuniculi ribosome.Muri E. cuniculi ribosome, iyi nucleotide ifata umwanya umwe na 25S rRNA A3186 nucleotide (Saccharomyces cerevisiae numero) mubindi byinshi bya ribosomes ya eukaryotic.b Mu miterere ya ribosomal ya E. cuniculi, iyi nucleotide iri hagati ya poroteyine ya ribosomal uL9 na eL20, bityo igahuza umubano hagati ya poroteyine zombi.cd eL20 isesengura ryibungabunga ryubwoko bwa microsporidia.Igiti cyitwa phylogeneque cyubwoko bwa Microsporidia (c) no guhuza byinshi bikurikirana bya poroteyine ya eL20 (d) byerekana ko ibisigazwa bya nucleotide bihuza ibisigazwa bya F170 na K172 bibikwa muri Microsporidia isanzwe, usibye S. lophii, usibye kwaguka kwa Microsporidia hakiri kare, yagumanye kwagura ES39L rRNA.e Iyi shusho yerekana ko ibisigazwa bya nucleotide F170 na K172 biboneka gusa muri eL20 ya genoside ya microsporidia yagabanutse cyane, ariko ntabwo iri mubindi eukaryote.Muri rusange, aya makuru yerekana ko ribosomes ya Microsporidian yateje imbere nucleotide ihuza urubuga rusa nkaho ruhuza molekile ya AMP ikanayikoresha muguhuza poroteyine-proteyine mu mikorere ya ribosomal.Kubungabunga cyane uru rubuga ruhuza Microsporidia no kutaboneka kwizindi eukaryote byerekana ko uru rubuga rushobora gutanga amahirwe yo kubaho kuri Microsporidia.Rero, umufuka wa nucleotide uhuza muri microsporidia ribosome ntabwo bigaragara ko ari ibintu byangirika cyangwa uburyo bwa nyuma bwo kwangirika kwa rRNA nkuko byasobanuwe mbere, ahubwo ni udushya tw’ubwihindurize butuma microsporidia ribosome ihuza mu buryo butaziguye molekile ntoya, ikayikoresha nk'ibice byubaka molekile.kubaka kubaka ribosomes.Ubu buvumbuzi butuma microsporidia ribosome ribosome yonyine izwiho gukoresha nucleotide imwe nkibice byubaka.f Inzira yubwihindurize ikomoka kuri nucleotide guhuza.
Ubucucike bwa kabiri buke bwa molekuline buri hagati yimbere ya poroteyine ya ribosomal uL9 na eL30 (Ishusho 5a).Iyi interface yasobanuwe mbere muburyo bwa Saccharomyces cerevisiae ribosome nkurubuga ruhuza nucleotide ya 25S ya rRNA A3186 (igice cyagutse cya ES39L rRNA) 38.Byerekanwe ko muburyo bubi P. locustae ES39L ribosomes, iyi interface ihuza nucleotide imwe itazwi 31, kandi hafatwa ko iyi nucleotide yagabanutse muburyo bwa nyuma bwa rRNA, aho uburebure bwa rRNA ari ~ 130-230.ES39L yagabanutse kuri nucleotide imwe 32.43.Amashusho yacu ya cryo-EM ashyigikira igitekerezo cyuko ubucucike bushobora gusobanurwa na nucleotide.Nyamara, imyanzuro ihanitse yimiterere yacu yerekanaga ko iyi nucleotide ari molekile idasanzwe, bishoboka ko ari AMP (Ishusho 5a, b).
Twahise tubaza niba urubuga rwa nucleotide ruhuza rwagaragaye muri E. cuniculi ribosome cyangwa niba rwabayeho mbere.Kubera ko guhuza nucleotide ahanini byahujwe n’ibisigisigi bya Phe170 na Lys172 muri proteine ​​ya eL30 ya ribosomal, twasuzumye kubungabunga ibyo bisigazwa muri eukaryote ihagarariye 4396.Nkuko byagenze kuri uL15 hejuru, twasanze ibisigazwa bya Phe170 na Lys172 bibitswe cyane muri Microsporidia isanzwe, ariko ntibiboneka mu zindi eukaryote, harimo Microsporidia Mitosporidium na Amphiamblys, aho igice cya ES39L rRNA kitagabanijwe 44, 45, 46 (Ishusho 5c).-e).
Ufatiye hamwe, aya makuru ashyigikira igitekerezo cyuko E. cuniculi ndetse na microsporidia ishobora kuba yarahinduye ubushobozi bwo gufata neza umubare munini wa metabolite ntoya mu miterere ya ribosome kugirango yishyure igabanuka rya rRNA na proteyine.Mu kubikora, bateje imbere ubushobozi budasanzwe bwo guhuza nucleotide hanze ya ribosome, byerekana ko imiterere ya molekile ya parasitike yishyura ifata metabolite ntoya kandi ikayikoresha nk'imiterere yimiterere ya RNA yangiritse kandi ibice bya poroteyine..
Igice cya gatatu kitagereranijwe cyikarita yacu ya cryo-EM, dusanga muri subunit nini ya ribosomal.Ikigereranyo kiri hejuru cyane (2,6 Å) yikarita yacu cyerekana ko ubwo bucucike ari ubwa poroteyine zifite imiterere yihariye y’ibisigarira binini by’uruhererekane, byadushoboje kumenya ubwo bucucike nka poroteyine ya ribosomal yari itaramenyekana twamenyekanye nka Yiswe msL2 (Microsporidia- proteine ​​yihariye L2) (uburyo, ishusho ya 6).Ubushakashatsi bwakozwe na homology bwerekanye ko msL2 ibitswe muri classe ya Microsporidia yo mu bwoko bwa Encephaliter na Orosporidium, ariko ikaba idahari mu yandi moko, harimo na Microsporidia.Mu miterere ya ribosomal, msL2 ifata icyuho cyatewe no gutakaza ES31L rRNA yaguye.Muri iki cyuho, msL2 ifasha guhagarika ububiko bwa rRNA kandi irashobora kwishyura indishyi za ES31L (Ishusho 6).
ubucucike bwa Electron nicyitegererezo cya Microsporidia yihariye ya poroteyine ya ribosomal msL2 iboneka muri E. cuniculi ribosomes.b Ibyinshi muri eukaryotic ribosomes, harimo na 80S ribosome ya Saccharomyces cerevisiae, ifite amplification ya ES19L rRNA yatakaye mubwoko bwinshi bwa Microsporidian.Imiterere yashizweho mbere ya microsporidia V. necatrix microsporidia ribosome yerekana ko gutakaza ES19L muri izi parasite byishyurwa nihindagurika rya poroteyine nshya ya msL1 ribosomal.Muri ubu bushakashatsi, twasanze E. cuniculi ribosome yanateje imbere poroteyine ya ribosomal RNA yongeyeho nka indishyi zigaragara zo gutakaza ES19L.Nyamara, msL2 (kuri ubu isobanurwa nka hypothetical ECU06_1135 proteine) na msL1 bifite inkomoko zitandukanye zubwihindurize.c Ubu buvumbuzi bwibisekuru bya poroteyine ya msL1 na msL2 bitajyanye nubwihindurize byerekana ko niba ribosomes zegeranije ihinduka ry’imiterere mibi muri rRNA yabo, zishobora kugera ku ntera zitigeze zibaho z’ibinyabuzima bitandukanye ndetse no mu gice gito cy’ibinyabuzima bifitanye isano rya bugufi.Ubu buvumbuzi bushobora gufasha gusobanura inkomoko nubwihindurize bwa ribosome ya mitochondrial, izwiho kuba yagabanutse cyane rRNA hamwe n’imihindagurikire idasanzwe mu bigize poroteyine ku binyabuzima.
Twahise tugereranya poroteyine ya msL2 na poroteyine ya msL1 yasobanuwe mbere, poroteyine imwe rukumbi izwi ya microsporidia yihariye ya ribosomal iboneka muri V. necatrix ribosome.Twashakaga kugerageza niba msL1 na msL2 bifitanye isano nubwihindurize.Isesengura ryacu ryerekanye ko msL1 na msL2 zifata umwobo umwe mu miterere ya ribosomal, ariko zikaba zifite ibyiciro byibanze na za kaminuza zitandukanye, byerekana inkomoko yabo yigenga (Ishusho 6).Kubwibyo, kuvumbura msL2 bitanga gihamya yerekana ko amatsinda yubwoko bworoshye bwa eukaryotique ashobora kwigenga yigenga yihinduranya poroteyine zitandukanye za ribosomal kugirango yishyure igihombo cya rRNA.Ubu bushakashatsi burazwi cyane ko cytoplasmeque eukaryotic ribosomes irimo proteine ​​idahinduka, harimo umuryango umwe wa poroteyine 81 za ribosomal.Kugaragara kwa msL1 na msL2 mubice bitandukanye bya microsporidia mugusubiza igihombo cyagutse cya rRNA byerekana ko kwangirika kwimyubakire ya molekile ya parasite bitera parasite gushaka ihinduka ryindishyi, amaherezo bikabaviramo no kubona mubantu batandukanye ba parasite.imiterere.
Hanyuma, igihe icyitegererezo cyacu cyarangiye, twagereranije ibice bya E. cuniculi ribosome nibyahanuwe uhereye kuri genome.Poroteyine nyinshi za ribosomal, harimo eL14, eL38, eL41, na eS30, mbere batekerezaga ko zabuze muri genom ya E. cuniculi kubera ko bigaragara ko nta homologologi zabo zabayeho muri gen E. cuniculi.Gutakaza poroteyine nyinshi za ribosomal nazo zirahanurwa mubindi byinshi bigabanuka cyane parasite yo mu nda na endosymbionts.Kurugero, nubwo bagiteri nyinshi zidafite ubuzima zirimo umuryango umwe wa poroteyine 54 za ribosomal, 11 muri iyo miryango ya poroteyine ni zo zonyine zifite imiterere ya homologues muri buri genome yasesenguwe na bagiteri zabujijwe.Mu rwego rwo gushyigikira iki gitekerezo, igihombo cya poroteyine ya ribosomal cyagaragaye mu bushakashatsi muri V. necatrix na P. locustae microsporidia, idafite proteine ​​za eL38 na eL4131.32.
Nyamara, imiterere yacu yerekana ko eL38, eL41, na eS30 byonyine byazimiye muri E. cuniculi ribosome.Poroteyine ya eL14 yarazigamwe kandi imiterere yacu yerekanaga impamvu iyi poroteyine idashobora kuboneka mugushakisha homologiya (Ishusho 7).Muri E. cuniculi ribosomes, igice kinini cya eL14 gihuza kibuze kubera kwangirika kwa rRNA-yongerewe ES39L.Mugihe ES39L idahari, eL14 yatakaje igice kinini cyayo ya kabiri, kandi 18% gusa bya eL14 byakurikiranye byari bisa muri E. cuniculi na S. cerevisiae.Uku kubungabunga nabi gukurikiranye biratangaje kuko na Saccharomyces cerevisiae na Homo sapiens-ibinyabuzima byahindutse imyaka miriyari 1.5 itandukanye - bisangiye hejuru ya 51% byibisigisigi bimwe muri eL14.Uku gutakaza bidasanzwe kubungabunga ibidukikije bisobanura impamvu E. cuniculi eL14 isobanurwa nka poroteyine ya M970_061160 kandi atari nka poroteyine ya eL1427.
na Microsporidia ribosome yatakaje ES39L rRNA yaguye, ikuraho igice cya eL14 ribosomal protein ihuza urubuga.Mugihe ES39L idahari, poroteyine ya eL14 ya microspore igira igihombo cyimiterere yinyongera, aho icyahoze cyitwa rRNA gihuza α-helix cyangirika mukigero gito.b Guhuza inshuro nyinshi byerekana ko poroteyine ya eL14 ibitswe cyane mu bwoko bwa eukaryotique (57% bikurikirana hagati yumusemburo na homologues yabantu), ariko ntibibungabunzwe nabi kandi bitandukanye muri microsporidia (aho bitarenze 24% byibisigara bisa na eL14 homologue).kuva S. cerevisiae cyangwa H. sapiens).Uku kubungabunga gukurikiranye nabi hamwe nuburyo butandukanye bwo guhindura imiterere bisobanura impamvu homologue ya eL14 itigeze iboneka muri E. cuniculi n'impamvu iyi proteine ​​ikekwa ko yatakaye muri E. cuniculi.Ibinyuranye, E. cuniculi eL14 yabanje gutangazwa nka poroteyine M970_061160.Ubu bushakashatsi bwerekana ko microsporidia itandukanye ya genome itandukanijwe muri iki gihe: genes zimwe na zimwe zitekereza ko zabuze muri microsporidia mu byukuri zarazigamwe, nubwo zaba zitandukanye;Ahubwo, bamwe batekereza kode ya microsporidia genes ya poroteyine yihariye yinyo (urugero, proteine ​​hypothetique M970_061160) mubyukuri kode ya poroteyine zitandukanye ziboneka mu zindi eukaryote.
Ubu bushakashatsi bwerekana ko gutandukana kwa RRNA bishobora gutera igihombo gikomeye cyo kubungabunga urutonde rwa poroteyine zegeranye na ribosomal, bigatuma izo poroteyine zitamenyekana mu gushakisha homologiya.Rero, dushobora kugereranya urugero nyarwo rwo kwangirika kwa molekile mu binyabuzima bito bya genome, kubera ko poroteyine zimwe na zimwe zitekereza ko zabuze zikomeza kubaho, nubwo zahinduwe cyane.
Nigute parasite ishobora kugumana imikorere yimashini za molekile mugihe cyo kugabanuka kwa genome bikabije?Ubushakashatsi bwacu busubiza iki kibazo dusobanura imiterere ya molekulire igoye (ribosome) ya E. cuniculi, ikinyabuzima gifite imwe muri genoside ntoya ya eukaryotic.
Byari bimaze imyaka igera kuri makumyabiri bizwi ko molekile ya poroteyine na RNA muri parasite ya mikorobe ikunze gutandukana na molekile zabo zo mu bwoko bwa homologique mu moko atabaho ku buntu kuko zidafite ibigo bigenzura ubuziranenge, zigabanuka kugera kuri 50% by'ubunini bwazo muri mikorobe zidafite ubuzima, n'ibindi.ihinduka ryinshi ryimiterere ihindura imitsi n'imikorere.Kurugero, ribosomes yibinyabuzima bito bito, harimo parasite nyinshi zo mu nda na endosymbionts, byitezwe kubura proteine ​​nyinshi za ribosomal ndetse kugeza kuri kimwe cya gatatu cya nucleotide ya rRNA ugereranije nubwoko bwubuzima bwisanzuye 27, 29, 30, 49. Icyakora, uburyo izo molekile zikora muri parasite bikomeza kuba amayobera, byizwe ahanini na genomika igereranya.
Ubushakashatsi bwacu bugaragaza ko imiterere ya macromolecules ishobora guhishura ibintu byinshi byabayeho biturutse ku bwihindurize bigoye kuvana mu bushakashatsi bwa genoside bugereranya bwa parasite yo mu nda ndetse n’ibindi binyabuzima byabujijwe kubakira (Ishusho yinyongera 7).Kurugero, urugero rwa poroteyine ya eL14 yerekana ko dushobora kugereranya urugero nyarwo rwo kwangirika kwimikorere ya molekile mu bwoko bwa parasitike.Encephalitis parasite ubu bemeza ko ifite amagana ya microsporidia yihariye.Ariko, ibisubizo byacu byerekana ko zimwe murizo gen zisa nkizisanzwe mubyukuri bitandukanye cyane na gen zisanzwe mubindi eukaryote.Byongeye kandi, urugero rwa poroteyine ya msL2 yerekana uburyo twirengagiza poroteyine nshya za ribosomal no gupfobya ibiri mu mashini ya parasitike.Urugero rwa molekile ntoya yerekana uburyo dushobora kwirengagiza udushya twinshi mubikorwa bya parasitike ya parasitike ishobora kubaha ibikorwa bishya byibinyabuzima.
Dufatiye hamwe, ibisubizo biradufasha kumva neza itandukaniro riri hagati yimiterere ya molekile yibinyabuzima byabujijwe kwakirwa na bagenzi babo mubinyabuzima bidafite ubuzima.Twerekana ko imashini ya molekile, yatekerejweho kugabanuka, kwangirika, no gukurikiza ihinduka ryimiterere ihindagurika, ahubwo ifite urutonde rwibintu byirengagijwe muburyo budasanzwe.
Ku rundi ruhande, ibice bya rRNA bitari byinshi hamwe n’ibice byahujwe twasanze muri ribosomes ya E. cuniculi byerekana ko kugabanya genome bishobora guhindura ndetse ibyo bice byimashini zifatizo za molekuline zabitswe mubice bitatu byubuzima - nyuma yimyaka miriyari 3,5.ubwihindurize bwigenga bwibinyabuzima.
Ibice bya RRNA bitagira umubyimba kandi byahujwe muri E. cuniculi ribosomes birashishikaje cyane ukurikije ubushakashatsi bwakozwe mbere na molekile ya RNA muri bagiteri ya endosymbiotic.Kurugero, muri aphid endosymbiont Buchnera aphidicola, molekile ya rRNA na tRNA byagaragaye ko ifite imiterere-yubushyuhe bukabije bitewe na A + T ibogamye hamwe nigice kinini cyibintu bidafite ishingiro 20,50.Izi mpinduka muri RNA, kimwe nimpinduka za molekile za poroteyine, ubu biratekerezwa kuba nyirabayazana yo kurenza urugero kwa endosymbionts ku bafatanyabikorwa ndetse no kuba endosymbionts idashobora kohereza ubushyuhe 21, 23.Nubwo microsporidia parasitike rRNA ifite impinduka zitandukanye muburyo, imiterere yizo mpinduka yerekana ko kugabanya ubushyuhe bwumuriro no guterwa na poroteyine za chaperone bishobora kuba ibintu bisanzwe biranga molekile ya RNA mubinyabuzima hamwe na genoside yagabanutse.
Ku rundi ruhande, imiterere yacu yerekana ko microsporidia ya parasite yahinduye ubushobozi budasanzwe bwo kurwanya ibice bya RRNA hamwe na poroteyine zabitswe cyane, biteza imbere ubushobozi bwo gukoresha metabolite ntoya kandi byoroshye kuboneka nka mimitike yimiterere ya rRNA yangirika nibice bya poroteyine.Imiterere ya molekulari..Iki gitekerezo gishyigikiwe nuko molekile nto zishyura igihombo cya proteine ​​muri rRNA na ribosomes ya E. cuniculi ihuza ibisigazwa byihariye bya microsporidia muri proteine ​​za uL15 na eL30.Ibi byerekana ko guhuza molekile nto na ribosomes bishobora kuba umusaruro wo guhitamo neza, aho hatoranijwe ihinduka ryihariye rya Microsporidia muri poroteyine za ribosomal kubera ubushobozi bwazo bwo kongera isano ya ribosomes kuri molekile nto, zishobora gutuma ibinyabuzima bya ribosoma bikora neza.Ubuvumbuzi bugaragaza udushya twiza mumiterere ya molekile ya parasite kandi biduha gusobanukirwa neza nuburyo imiterere ya molekile ya parasite ikomeza imikorere yayo nubwo habayeho ubwihindurize.
Kugeza ubu, kumenyekanisha izo molekile nto ntibisobanutse neza.Ntabwo byumvikana impamvu isura ya molekile nto mumiterere ya ribosomal itandukanye hagati yubwoko bwa microsporidia.By'umwihariko, ntibisobanutse impamvu guhuza nucleotide bigaragara muri ribosomes ya E. cuniculi na P. locustae, kandi ntabwo biri muri ribosomes ya V. necatrix, nubwo hasigaye F170 muri proteine ​​za eL20 na K172 za V. necatrix.Uku gusiba gushobora guterwa n ibisigara 43 uL6 (biherereye hafi ya nucleotide ihuza umufuka), ari tyrosine muri V. necatrix ntabwo ari threonine muri E. cuniculi na P. locustae.Urunigi runini rwa Aromatic urunigi rwa Tyr43 rushobora kubangamira nucleotide guhuza bitewe na steric overlap.Ubundi, gusiba nucleotide bigaragara ko bishobora guterwa no gukemuka guke kwishusho ya cryo-EM, bikabuza kwerekana ibice bya V. necatrix ribosomal.
Kurundi ruhande, akazi kacu karerekana ko inzira yo kubora genome ishobora kuba imbaraga zo guhanga.By'umwihariko, imiterere ya E. cuniculi ribosome yerekana ko gutakaza ibice bya rRNA hamwe na poroteyine muri microsporidia ribosome bitera umuvuduko w’ubwihindurize utera impinduka mu miterere ya ribosome.Izi variants zibaho kure yikibanza gikora cya ribosome kandi bigaragara ko zifasha kubungabunga (cyangwa kugarura) inteko nziza ya ribosome yakagombye guhungabana no kugabanuka kwa RRNA.Ibi birerekana ko udushya twinshi twa microsporidia ribosome bigaragara ko yahindutse bikenewe gukenera gene drift.
Ahari ibi bigaragazwa neza no guhuza nucleotide, itigeze igaragara mubindi binyabuzima kugeza ubu.Kuba ibisigazwa bya nucleotide bihuza biboneka muri microsporidia isanzwe, ariko ntibiboneka mu zindi eukaryote, byerekana ko imbuga za nucleotide zihuza atari ibisigisigi bitegereje kuzimira, cyangwa ikibanza cya nyuma kugirango rRNA isubizwe muburyo bwa nucleotide.Ahubwo, uru rubuga rusa nkibintu byingirakamaro byashoboraga guhinduka muburyo butandukanye bwo guhitamo ibyiza.Imbuga za Nucleotide zishobora kuba ibicuruzwa biva mu gutoranya bisanzwe: ES39L imaze kwangirika, microsporidia ihatirwa gushaka indishyi zo kugarura ibinyabuzima byiza bya ribosome mugihe ES39L idahari.Kubera ko iyi nucleotide ishobora kwigana imikoranire ya molekile ya nucleotide ya A3186 muri ES39L, molekile ya nucleotide ihinduka inyubako ya ribosome, guhuza kwayo kurushaho kunozwa no guhindura ihinduka rya eL30.
Ku bijyanye nihindagurika rya molekuline ya parasite idasanzwe, ubushakashatsi bwacu bwerekana ko imbaraga zo gutoranya kamere ya Darwin no gutembera kwa genetike zangirika zidakora mu buryo bumwe, ahubwo zinyeganyega.Ubwa mbere, drift genetique ikuraho ibintu byingenzi biranga biomolecules, bigatuma indishyi zikenewe cyane.Gusa iyo parasite ihagije ibyo ikeneye binyuze mu gutoranya kamere ya Darwin, macromolecules yabo izaba ifite amahirwe yo guteza imbere imico yabo itangaje kandi igezweho.Icy'ingenzi, ubwihindurize bwibibanza bya nucleotide bihuza muri E. cuniculi ribosome byerekana ko ubu buryo bwo gutakaza-inyungu-bwihindurize bwa molekuline butagabanya gusa ihinduka ryimiterere ihindagurika, ariko rimwe na rimwe butanga imirimo mishya kuri macromolecules ya parasitike.
Iki gitekerezo gihuye nigitekerezo cya Sewell Wright kigenda kiringaniza kiringaniye, kivuga ko uburyo bukomeye bwo gutoranya kamere bugabanya ubushobozi bwibinyabuzima guhanga udushya 51,52,53.Ariko, niba gutondekanya genetike bihagarika guhitamo kwa kamere, izi drift zirashobora kubyara impinduka zitari ubwazo zijyanye no guhuza n'imiterere (cyangwa zangiza) ariko biganisha ku zindi mpinduka zitanga ubuzima bwiza cyangwa ibikorwa bishya byibinyabuzima.Urwego rwacu rushyigikira iki gitekerezo mugaragaza ko ubwoko bumwe bwa mutation bugabanya inshuro n'imikorere ya biomolecule bigaragara ko aribwo buryo nyamukuru bwo kuyitezimbere.Dukurikije icyerekezo cyubwihindurize-win, ubushakashatsi bwacu bwerekana ko kwangirika kwa genome, bisanzwe bifatwa nkigikorwa cyo kwangirika, nabwo ni moteri ikomeye yo guhanga udushya, rimwe na rimwe ndetse wenda ikanemerera macromolecules kubona ibikorwa bishya bya parasitike.irashobora kubikoresha.