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Genetik kodning ortiqchaligi

Genetik kodning ortiqchaligi


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Ma'lum bir kodon faqat bitta aminokislota uchun kodlanadi, ammo aminokislota bir nechta turli kodonlar tomonidan kodlanishi mumkin. Endi genetik kodga ko'ra, kodonUUUaminokislota fenilalanin uchun kodlar vaUUAleysin uchun kodlar. Ammo, Wobble gipotezasiga ko'ra, kodonning uchinchi pozitsiyasi va antikodondagi asos bir-birini to'ldiruvchi bo'lishi shart emas (bu 61 ta kodon bo'lishiga qaramay, nima uchun tRNK molekulalarining juda oz turlari mavjudligini tushuntirishga yordam beradi). Agar bu gipoteza to'g'ri bo'lsa, u holda biz fenilalaninni leytsin uchun mo'ljallangan joyga qo'yishimiz mumkin va aksincha (chunki ularni kodlaydigan kodonlar faqat uchinchi asosda farqlanadi). Xuddi shu narsa aspartik kislota va glutamik kislota va serin va arginin kabi juftlarga ham tegishli. Xo'sh, qanday qilib ma'lum bir mRNK molekulasining tarjimasi to'g'ri polipeptid ketma-ketligini keltirib chiqaradi?


Wobble juftligi shunchaki hodisa bo'lib, qattiq va tezkor qoida emas. Nima uchun mavjud bo'lishi kerakligi haqida ba'zi asoslar mavjud va shuning uchun u hali ham gipoteza deb ataladi. Va bu bayonot to'g'ri emas: "kodonning uchinchi pozitsiyasidagi va antikodondagi asos bir-birini to'ldiruvchi bo'lishi shart emas". Kodonning uchinchi qoldig'iga mos keladigan antikodon qoldig'i a bo'lishi mumkin behayo ikki yoki bir nechta turli asoslar bilan birlasha oladigan tayanch. Fenilalanin uchun tRNK antikodonga ega -GAAikkalasi bilan birlashishi mumkinUUUvaUUClekin emasUUA.

Shunday qilib, tebranish gipotezasi shundan iboratki, antikodonning birinchi bazasi (ko'pincha o'zgartirilgan/atipik nukleobazalar) bog'lanishning nopokligini ko'rsatishi mumkin.


Toʻgʻri aytasizki, Krik oʻzining “Vobble gipotezasi”da “kodonning uchinchi holatidagi asos va antikodonning asosi bir-birini toʻldiruvchi boʻlishi shart emas”, deb taklif qilgan, ammo "bo'lishi shart emas" Sizning bayonotingizda ning parafrazi mavjud "biroz" Krikning asl bayonotida:

“Taklif qilinadiki, standart tayanch juftliklari uchlikning dastlabki ikki pozitsiyasida qatʼiy qoʻllanilishi mumkin boʻlsa-da, biroz uchinchi tayanch juftligida chayqalish.

Agar siz ushbu qog'ozni o'qisangiz - yoki Wobble ostidagi Vikipediya yozuviga murojaat qilsangiz, Krik "ba'zi" so'zini ishlatayotganini bilib olasiz:

(i) Taklif etilayotgan tebranish ma'lum tayanch juftliklar uchun xosdir.

(ii) Bunday tebranish asoslari juftlari faqat genetik kodni buzmagan hollarda topiladi.

The Wobble Gipoteza - yuqorida aytib o'tilganidek - to'g'ri ekanligi aniq ko'rsatilgan. Maxsus Wobble Qoidalar Krik (i) bandini qondirish uchun taklif qilgan asoslar kimyosini tekshirishga asoslangan va qisman to'g'ri ekanligi ko'rsatilgan:

Wobble qoidalari: Krikning kelib chiqishi bashorati kuzatilgan 5'-antikodon asoslari va ularning kodonlar bilan tayanch juftligi bilan solishtirganda.

Shunday qilib, 5'-tRNK antikodon asoslari, G va men chayqalishi mumkin (va C bo'lishi mumkin emas) degan bashorat amalga oshdi. Krik antikodonlarda bu holatda A ning kamligini bilar edi va u ham, U ham odatda kimyoviy jihatdan o'zgartirilgan shakllarda topiladi, ularning asosiy juftligini u bashorat qilishga urinmagan (u ularning aksariyatini bilmagan) va qaysi turli hollarda farqlanadi. Esda tutish kerak bo'lgan narsa shundaki, buning uchun tRNKdagi antikodonning uch o'lchovli tuzilishi (birinchi ikkita bazani asosiy stacking orqali ushlab turadi) va potentsial vodorod bog'lovchi guruhlarning yaqinligi nuqtai nazaridan ilmiy asos bor. turli asoslarda.

(ii) nuqta shundan iboratki, tabiat faqat genetik kod ruxsat bergan joyda Wobble-dan foydalanadi. C yoki U bilan G juftligi har doim ishlaydi, I, A, C yoki G bilan bog‘lash esa blokdagi barcha to‘rtta asos (masalan, Leu, Val, Ser) tomonidan kodlangan aminokislotalar bilan ishlaydi, lekin ikkita blok mavjud bo‘lganda emas (masalan, Tyr, His, Asn).

Bularning barchasining kimyoviy asosini ta'kidlaydigan yakuniy nuqta. Sutemizuvchilar mitoxondriyalari o'ziga xos tarzda kesilgan tRNKlari tufayli turli xil tebranish qoidalariga ega.


Genetik kodning ortiqchaligi - Biologiya

Ushbu bo'lim oxirida siz quyidagilarni amalga oshirishingiz mumkin:

  • Protein sintezining "markaziy dogma" ni tushuntiring
  • Genetik kodni va nukleotidlar ketma-ketligi aminokislotalar va oqsillar ketma-ketligini qanday belgilashini tasvirlab bering.

Transkripsiyaning hujayra jarayoni A, C, G va urasil (U) alifbosi bo'lgan bir yoki bir nechta genlarning mobil molekulyar nusxasi bo'lgan messenjer RNK (mRNK) ni hosil qiladi. mRNK shablonini tarjima qilish nukleotidga asoslangan genetik ma'lumotni oqsil mahsulotiga aylantiradi. Proteinlar ketma-ketligi 20 ta tez-tez uchraydigan aminokislotalardan iborat, shuning uchun protein alifbosi 20 ta harfdan iborat deb aytish mumkin (1-rasm). Har bir aminokislota triplet kodon deb ataladigan uch nukleotidli ketma-ketlik bilan belgilanadi. Turli xil aminokislotalar turli xil kimyoviy moddalarga ega (masalan, kislotali va asosiy yoki qutbli va qutbsiz) va turli xil strukturaviy cheklovlar. Aminokislotalar ketma-ketligining o'zgarishi oqsil tuzilishi va funktsiyasida juda katta o'zgarishlarga olib keladi.

Shakl 1. Oqsillarda joylashgan 20 ta aminokislotalarning tuzilishi ko'rsatilgan. Har bir aminokislota aminokislotalardan iborat (NH+ 3), karboksil guruhi (COO -) va yon zanjir (ko'k). Yon zanjir qutbsiz, qutbli yoki zaryadlangan, shuningdek, katta yoki kichik bo'lishi mumkin. Bu protein tuzilishi va funktsiyasining ajoyib o'zgarishiga olib keladigan aminokislotalar yon zanjirlarining xilma-xilligi.


10.4: Genetik kod

  • E. V. Vong tomonidan kiritilgan
  • Axolotl Academica nashriyoti (biologiya) Axolotl Academica nashriyoti

Biz DNK xromosomalarining maqsadini hujayra oqsillarini yaratish uchun ma'lumotni olib yurish, RNK esa buning uchun vositachi sifatida tasvirlab berdik. To'g'ri, to'rt xil nukleotidlardan tashkil topgan molekula (ular minglab va hatto minglab bo'lsa ham) hujayraga yigirmata aminokislotadan qaysi biri birlashib, funktsional oqsil hosil qilishini ayta oladi. ? Aniq yechim shundaki, har bir aminokislota uchun kodlash uchun individual noyob nukleotidlar etarli emasligi sababli, ma'lum aminokislotalarni belgilaydigan nukleotidlarning kombinatsiyasi bo'lishi kerak. Dublet kod faqat 16 xil kombinatsiyani (birinchi pozitsiyada 4 ta mumkin bo'lgan nukleotid x ikkinchi holatda 4 ta mumkin bo'lgan nukleotid = 16 kombinatsiya) imkonini beradi va 20 ta aminokislotalarni kodlash uchun etarli bo'lmaydi. Biroq, triplet kod 20 ta aminokislotalarni kodlash uchun 64 ta kombinatsiyani beradi. To'rtlik yoki beshlik kod ham shunday bo'ladi, lekin ular resurslarni isrof qiladi va shuning uchun kamroq bo'ladi. Keyingi tekshiruvlar quyidagi jadvalda tavsiflanganidek, uchlik kodning mavjudligini isbotladi.

Juda ko'p birikmalar va atigi 20 ta aminokislotalar bilan hujayra boshqa imkoniyatlar bilan nima qiladi? Genetik kod a degenerativ kod, bu ko'p aminokislotalarning bir nechta triplet birikmalari (kodon) bilan kodlanganligi uchun ortiqcha borligini anglatadi. Garchi bu ortiqcha kod bo'lsa-da, u noaniq kod emas: oddiy sharoitda berilgan kodon bitta va faqat bitta aminokislotani kodlaydi. 20 ta aminokislotadan tashqari, tarjimani tugatishga bag'ishlangan uchta &ldquostop kodonlari&rdquo ham mavjud. Uchta to'xtash kodonlari ham so'zlashuv nomlariga ega: UAA (oxra), UAG (qahrabo), UGA (opal), UAA prokaryotik genlarda eng keng tarqalgan.

UAG kashfiyotchilari kodonni familiyasi &ldquoamber&rdquo ga tarjima qilingan do'stlarining nomini berishga qaror qilganlarida, so'zlashuv ismlari boshlangan. To'xtash kodonlariga rang nomlarini berish g'oyasini davom ettirish uchun opal va ocher nomi berildi.

To'xtash kodonlari ba'zan hozirda 21 va 22-chi aminokislotalar, selenosistein (UGA) va pirrolizin (UAG) deb hisoblangan narsalarni kodlash uchun ham ishlatiladi. Ushbu aminokislotalar prokarya va arxeyaning ba'zi turlarida doimiy ravishda kodlanganligi aniqlangan.

E'tibor bering, maxsus boshlang'ich kodonlar mavjud emas: buning o'rniga, vaziyatga qarab metionin va tarjima boshlanishi uchun AUG kodlari, darhol tushuntirilgan. Dastlabki Met metionindir, ammo prokaryotlarda u maxsus modifikatsiyalangan formil-metionin (f-Met) dir. tRNK ham ixtisoslashgan va o'sib borayotgan polipeptidga qo'shilish uchun metioninni ribosomaga olib boradigan tRNKdan farq qiladi. Shuning uchun yuklangan inisiator tRNKga nisbatan odatiy nomenklatura fMet-tRNK hisoblanadi.i yoki fMet-tRNKf. Bundan tashqari, prokaryotlarda boshlang'ich joyni aniqlashda eukaryotlarga qaraganda bir oz ko'proq erkinlik mavjud, chunki ba'zi bakteriyalar GUG yoki UUG dan foydalanadi. Ushbu kodonlar odatda mos ravishda valin va leysinni kodlasa ham, ular boshlang'ich kodon sifatida ishlatilganda, inisiator tRNK f-Metni olib keladi.

Ta'riflangan genetik kod deyarli universal bo'lsa-da, ba'zi hollarda u o'zgartirilgan va o'zgarishlar evolyutsion barqaror muhitda saqlanib qolgan. Organizmlarning keng doirasidagi mitoxondriyalar genetik kodda barqaror o'zgarishlarni namoyish etadi, shu jumladan AGAni argininni kodlashdan to'xtash kodoniga aylantirish va AAAni lizinni kodlashdan asparaginni kodlashga o'zgartirish. Organizm (yadro) genomini tarjima qilishda kamdan-kam hollarda o'zgarish kuzatiladi, ammo bu kamdan-kam uchraydigan o'zgarishlarning aksariyati to'xtash kodonlariga yoki ulardan konversiyadir.

Genetik kodda boshqa kichik o'zgarishlar ham mavjud, ammo kodning universalligi saqlanib qolmoqda. Ba'zi mitoxondriyal DNKlar turli boshlang'ich kodonlardan foydalanishi mumkin: inson mitoxondrial ribosomalari AUA va AUU dan foydalanishi mumkin. Ba'zi xamirturush turlarida arginin uchun CGA va CGC kodonlari ishlatilmaydi. Ushbu o'zgarishlarning ko'pchiligi Milliy Biotexnologiya Axborot Markazi (NCBI) tomonidan mos ravishda Berklidagi Kaliforniya universiteti (AQSh) va Nagoya (Yaponiya) universitetida Jukes va Osava ishlariga asoslangan holda kataloglangan.


Neyron induksion embrion ildiz hujayralari

9.3.1 Sutemizuvchilarning ESKlarida neyroinduksiya

Sichqonchaning genetik tahlilining aniq dalillari bo'lmasa, asosan yuqorida muhokama qilingan genetik ortiqcha tufayli, ESClar sutemizuvchilarda neyron induktsiya uchun BMP inhibisyonining etarliligini hal qilish uchun eng mos modeldir. Hayvon qalpoqlarida bo'lgani kabi, sichqonchaning ham, odamning ham ESClarning farqlanishi germ qatlamlari va o'ziga xos hujayra turlarining paydo bo'lishida embrion rivojlanishini tartibga soluvchi signallarning ierarxik to'plamiga amal qiladi, deb taxmin qilish mumkin (Tomson va Marshall, 1998 Yu va Tomson, 2008).

Bu savolga qat'iy javob berish - umuman sutemizuvchilarning ESClarida va xususan, hESClarda - texnik cheklovlar bilan murakkablashdi. in vitro hujayra madaniyatining aspektlari. Masalan, mESC va hESC o'sish uchun zarur bo'lgan ozuqa moddalarini ta'minlash uchun 20% sarum ishtirokida muntazam ravishda o'stiriladi, shuning uchun ular allaqachon tashqi omillarning uzluksiz ta'siriga duchor bo'ladilar. Bundan tashqari, pluripotent mESC madaniyatlari pluripotent hESCs, Wnt, aktivin / nodal bilan bir qatorda leykemiya inhibitiv omil (LIF) va BMP'larni, shuningdek FGF ning juda yuqori darajasini talab qiladi (Singh va Brivanlou, 2010). Ushbu tashqi signalizatsiya talablari tahlilni sezilarli darajada murakkablashtiradi va neyron taqdiri spetsifikatsiyasining induktorlari va modifikatorlari o'rtasidagi farqda chalkashliklarni keltirib chiqaradi. Bundan tashqari, diagnostik hujayra taqdiri sifatida muntazam ravishda ishlatiladigan inson embrion taqdirining hujayra turiga xos molekulyar belgilari sichqon embrionlaridan ekstrapolyatsiya qilinadi. Inson embrionlarida ushbu belgilarning o'ziga xosligi to'g'ridan-to'g'ri tasdiqlanmaguncha, bu taxmin noto'g'ri bo'lishi mumkinligini yodda tutish kerak. Nihoyat, etishmasligi in vivo tasdiqlash uchun tahlillar in vitro kuzatish hESC holatlarida asosiy to'siqdir. ESClarning bir qatlamli yoki embrioid tanalar yoki teratomalar sifatida farqlanishi o'rnini bosa olmaydi. in vivo embrion tahlillari. In vitro madaniyat yoki o'smalar murakkab mikrob qatlami o'zaro ta'siri va yuzaga keladigan morfogenetik harakatlarga ega emas. in vivo, shuning uchun induktiv o'zaro ta'sirlarni osonlashtira olmaydi. Dizayn qilishga urinishlar in vivo juda erta sichqonchani / inson kimerizmini shakllantirish orqali hESC uchun tahlil mukammal o'rnini bosmaydi, chunki ular texnik cheklovlar va yomon omon qolishdan aziyat chekmoqda (Jeyms va boshq., 2006). Ushbu cheklovlarga qaramay, ESClar differentsiatsiya yo'llari haqidagi hozirgi tushunchamizda kuchli vosita ekanligi isbotlangan.

Sutemizuvchilarning ESC-larida neyron spetsifikatsiyaning molekulyar asoslariga bag'ishlangan tadqiqotlar uchta eksperimental paradigma atrofida aylanadi. Birinchisi, asabiy taqdirni keltirib chiqaradigan turli xil oziqlantiruvchi chiziqlarga ega ESC kokulturasi. Ikkinchisi, yuqori suyultirilgan qoplama (shu jumladan, bitta hujayra) yordamida ESClarni minimal muhitda o'stirish orqali uyali aloqani yo'q qilish yoki minimallashtirishga asoslanadi va shu bilan amfibiya hayvonlarining qopqog'i-hujayralarining dissotsiatsiyasi tajribalarini taqlid qiladi. Nihoyat, kokteyllar yoki individual omillar turli sharoitlarda o'stirilgan hujayralarga ularning nervlarni qo'zg'atuvchi faoliyatini sinab ko'rish uchun taqdim etiladi. Ushbu yondashuvlarning kombinatsiyasi BMP inhibisyonu sichqonchada ham, inson ESClarida ham asabiy taqdirni qo'zg'atish uchun etarli ekanligini ko'rsatish uchun muvaffaqiyatli ishlatilgan, bu BMP inhibisyonu va neyron standart modeli bo'yicha amfibiya ma'lumotlarini qo'llab-quvvatlaydi. Oxir-oqibat, shunga o'xshash xulosalarga kelsak, biz avval sichqonchani muhokama qilamiz va keyin standart modelga yaqinlashishdan oldin inson tajribalarini tasvirlaymiz.


Genetik ortiqchalikning evolyutsiyasi

Genetik ortiqchalik ikki yoki undan ortiq genning bir xil funktsiyani bajarishini va bu genlardan birining inaktivatsiyasi biologik fenotipga juda kam yoki umuman ta'sir qilmasligini anglatadi. Yuqori organizmlar genomlarida ortiqchalik keng tarqalgan ko'rinadi. Ko'rinib turibdiki, ortiqcha genlarga misollar rivojlanish biologiyasi, immunologiya, neyrobiologiya va hujayra siklining ko'plab tadqiqotlaridan olingan. Shunga qaramay, muammo bor: funktsional oqsillarni kodlaydigan genlar tanlov bosimi ostida bo'lishi kerak. Agar gen haqiqatan ham ortiqcha bo'lsa, u zararli mutatsiyalarning to'planishidan himoyalanmaydi. Shuning uchun bunday ortiqchalik evolyutsion barqaror bo'lishi mumkin emas degan keng tarqalgan fikr. Bu erda biz ortiqcha genlarga ta'sir qiluvchi tanlov bosimini tahlil qilish uchun oddiy genetik modelni ishlab chiqamiz. Biz genetik ortiqchalik nima uchun keng tarqalganligini tushuntira oladigan to'rtta holatni taqdim etamiz. Uchta holatda ortiqchalik hatto evolyutsion jihatdan barqarordir. Bizning nazariyamiz genetik tashkilotning evolyutsiyasini o'rganish uchun asos yaratadi.


Usullari

Model 1. Ikki lokusda genlarga ega haploid populyatsiyani ko'rib chiqing, A va B. Funktsional bo'lmagan allellar, a va b, mutatsiya tezligida paydo bo'ladi ua va ub. To'rtta genotip mavjud, AB, Ab, aB va ab. Chastotalar x1, x2, x3 va x4, va fitnes mavjud f1, f2, f3 va f4, mos ravishda. Har bir avlodda juftlashish (rekombinatsiya bilan), keyin mutatsiya va tanlov mavjud. Juftlanish farq tenglamalari bilan tavsiflanadi: x1 = x1 + D, x2 = x2D, x3 = x3D, va x4 = x4 + D. Bu yerda, D = r(x2x3x1x4), qayerda r orasidagi rekombinatsiya tezligi hisoblanadi A va B lokuslar va r 0 dan 0,5 gacha bo'lgan raqam. Mutatsiya tomonidan tavsiflanadi x1 = x1(1 − ua)(1 − ub), x2 = x1(1 − ua)ub + x2(1 − ua), x3 = x1ua(1 − ub) + x3(1 − ub), va x4 = x1uaub + x2ua + x3ub + x4. Tanlov tomonidan tavsiflanadi xi = fixi/f, qayerda f = Sixifi aholining o'rtacha jismoniy tayyorgarligini bildiradi. Aytaylik, ikkala gen ham funktsiyani bajaradi F teng samaradorlik bilan. Bizda ... bor f1 = f2 = f3 = 1 va f4 = 0. Mutatsiya tezligining aniq tengligi uchun, ua = ub = u, tomonidan berilgan muvozanat chizig'i mavjud x1 = x2x3r(1 − u)/u. Teng bo'lmagan mutatsiyalar uchun mutatsiya tezligi yuqori bo'lgan gen yo'q bo'lib ketadi.

Model 2. Bu model 1 bilan bir xil ramkaga ega, ammo genlar A va B funktsiyani bajarish F turli xil samaradorlik bilan, ha va hb. Mayli ha > hb. Genotip mosliklari f1 = f2 = ha, f3 = hb va f4 = 0. Ortiqchalik evolyutsion jihatdan barqaror bo'lishi mumkin, agar B nisbatan kamroq mutatsiya darajasiga ega A, ub < ua. Agar 1− (hb/ha) > ua > ub[1 + (1/r)(hahb)/hb] muvozanat x1 * = (1 − x2 * ) × [ha(1 − ua) − hb(1 − ub)] / [(hahb)(1 − ua)], x2 * = (1/r)[ub/(1 − ub) × [ha(1 − ua) − hb(1 − ub)] / [hb(uaub)], x3 * = 1 − x1 * − x2 * , va x4 * = 0. Mutatsiya tezligining pastligi uchun ortiqchaning muvozanat chastotasi AB genotip taxminan x1 * ≈ 1 − (1/r)[ub/(uaub)](hahb)/hb. Masalan, agar ha = 1, hb = 0.99, ua = 1.1 × 10 −6 , ub = 10 −6 va r = 0,5, keyin muvozanat chastotasi AB taxminan 0,8 ni tashkil qiladi.

Ushbu modelni kengaytirish mumkin n turli mutatsiya tezligi va har xil samaradorlikka ega genlar. Muayyan genotipning yaroqliligi eng samarali genning samaradorligi bilan ta'minlanadi. Agar kamroq samarali genlarda mutatsiyalar kamroq bo'lsa, bir nechta ortiqcha genlarning barqarorligi mumkin. Biroq, ko'p sonli genlar uchun samaradorlik va mutatsiya stavkalari bo'yicha shartlar juda cheklangan bo'ladi.

Model 3. Ikki genni ko'rib chiqing, A va B, va ikkita funktsiya, F1 va F2. Gen A funktsiyasini bajaradi F1 samaradorlik bilan ha, va gen B funktsiyasini bajaradi F1 past samaradorlik bilan hb va funksiya F2 bir samaradorlik bilan. Mutatsiyalar A harakatsiz variantga olib keladi a mutatsiya tezligi ua. Mutatsiyalar B variantga olib kelishi mumkin b1, funktsiyani bajarish qobiliyatini yo'qotgan F1 lekin baribir ijro etadi F2, yoki variantga b2, bu mutlaqo faol bo'lmagan mutatsiya stavkalari ub1 va ub2, mos ravishda. Variant b2 dan ham kelib chiqishi mumkin b1 mutatsiya tezligida ub3. Funktsiyani bajarish uchun ortiqcha tashkilot F1, evolyutsion jihatdan barqaror, agar ub1 < ua. Tahlil 2-modelga o'xshaydi, agar ub2ub3: past mutatsiyalar uchun muvozanat chastotasi AB taxminan hisoblanadi x1 * ≈ 1 − (1/r)[ub1/(uaub1)] × (hahb)/ha. 2-model bilan bir xil raqamli qiymatlar uchun va shunday deb faraz qilsak ub1 dan 10 marta kichikdir uaning muvozanat chastotasi ekanligini aniqlaymiz AB 0,998 ni tashkil qiladi. Pleiotropiya ortiqchalikni osonlashtiradi.

Model 4. Ikki genni ko'rib chiqing A va B mutatsiya tezligi bilan ua va ub va rivojlanish xatolik darajasi da va db. Mutatsiya va tanlanish farq tenglamalari bilan tavsiflanadi x1 = (1 - dadb)(1 − ua)(1 − ub)x1/f, x2 = (1 - da) × (x1ub + x2)/f, x3 = (1 - db)(1 − ub)(x1ua + x3)/f, x4 = 0, bu erda f shundaymi x1 + x2 + x3 = 1. 1-3 modellardan farqli o'laroq, bu erda rekombinatsiya muhim emas. ning muvozanat chastotasi AB hisoblanadi x1 = 1/<1 + [ua(1 - db)]/ [db(1 - da) − ua(1 - dadb)] + [ub(1 - da)] / [da(1 - db) − ub(1 - dadb)]>. ning kichik qiymatlari uchun u va d, biz olamiz x1 ≈ 1/<1 + [ua/(dbua)] + [ub/(daub)]>. Shunday qilib, katta uchun zarur shart-sharoitlar x1 bor ua < db va ub < da.

Modelni kengaytirish mumkin n genlar. Faraz qilaylik, barcha genlar mutatsiya tezligiga egau va rivojlanish xatolik darajasi d. Mayli xi bilan genotiplarni belgilang i genlar (i = 0,…, n). Aholi dinamikasi xnk = (fnk/f) Si = 0 k (ki ni ) × u ki xni, qayerda fj = (1 - d j )(1 − u) j va f shunday bo'ladiki, barcha chastotalar bittaga qo'shiladi. Muvozanatni rekursiv hal qilish mumkin. Hammasini o'z ichiga olgan genotip bilan muvozanat n ortiqcha genlar mumkin, agar fn > fn−1. Bu olib keladi n < 1 + (log u)/(log d).

Diploid modellar. Gaploid modellar bo'yicha natijalarimiz diploid modellarga ham tegishli. Diploid modellarda biz to'rtta gametani ajratamiz, AB, Ab, aB va ab, ular to'qqizta zigota hosil qiladi: AB/AB, AB/Ab, Ab/Ab, AB/aB, aB/aB, AB/ab, Ab/ab, aB/ab va ab/ab. Har bir avlod uchun mutatsiya gametalar chastotasiga ta'sir qiladi, keyin zigotalar hosil bo'ladi, seleksiya zigotalarga ta'sir qiladi va nihoyat yangi gametalar hosil bo'ladi, shu jumladan rekombinatsiya imkoniyati. Gaploid 1-model bilan kelishilgan holda, biz barcha zigotalarning yuqori fitnesga ega ekanligini aniqlaymiz ab/ab kam fitnesga ega bo'lgan, barqaror ortiqchalikka olib kelmaydi. 2 va 3-modellarga o'xshash holatlar barqaror ortiqchalikni beradi. Rivojlanish xatolari bo'lgan diploid modellar ham barqaror ortiqchalikni beradi.

Diploid modellarda ortiqcha bo'lishiga olib keladigan qo'shimcha holatlar mavjud. Bunday holatlardan biri Brukfild tomonidan kashf etilgan: u qo'sh geterozigota deb taxmin qiladi, AB/ab, yovvoyi tur kabi mos keladi, AB/AB, lekin Ab/ab, aB/ab va ab/ab 1 . Bundan tashqari, barqaror ortiqchalik qisman dominantlik uchun ham mumkin, bunda barcha homozigotlar yuqori fitnesga ega, er-xotin geterozigotalar kamroq mosliklarga ega, bitta geterozigotalar hali ham pastroq fitnesga ega va. ab/ab eng past jismoniy holatga ega.

Ortiqchalikning tasnifi. Genetik ortiqchalikning uch turini ajratish foydalidir. (1) Haqiqiy ortiqchalik 1 ortiqcha genotipga ega bo'lgan shaxsning holatini bildiradi. AB, ortiqcha genlardan biri nokaut qilinganidan ko'ra mos emas, Ab. 2-modelda, B haqiqatan ham ortiqcha, lekin A emas. Pleiotropiya bo'lgan hollarda "haqiqiy ortiqcha" to'liq ortiqcha genotip bitta genning pleiotrop funktsiyasi yo'q qilingan genotipga qaraganda mos emasligini anglatadi. (2) "Umumiy ortiqcha" - bu an AB individual faqat vaqti-vaqti bilan birdan mos keladi Ab individual. Bu kamdan-kam rivojlanish xatolarining natijasi bo'lishi mumkin. Yana bir imkoniyat - bu AB dan mos keladi Ab ba'zi muhitlarda. (3) "Deyarli ortiqcha" ortiqcha genotipga qaraganda AB har doim ortiqcha genlardan biri nokaut qilingan har qanday genotipga qaraganda bir oz mos keladi. Albatta, agar vaziyat ortiqcha deb hisoblansa, fitnes farqi kichik bo'lishi kerak. Bir qancha bunday misollar avvalroq muhokama qilingan 5 .


Ribosomal translatsion katlamaning dixotomiyasi

Mexanik ko'rinish

Bir qator tadqiqotlar shuni ko'rsatadiki, ribosomalar yangi paydo bo'lgan zanjirlardagi strukturaviy shakllanishlarni rivojlantirish uchun bir nechta yo'llardan foydalanadi. Ribosomalar spiral shakllanishiga yordam berishi mumkin (Woolhead va boshq., 2004), hibsga olingan tug'ilgan zanjirlarning siqilishi (Lu va Deutsch, 2005) va ikkilamchi va ba'zi uchinchi darajali tuzilmalarning birgalikda tarjimasi shakllanishi (Evans va boshqalar, 2008 Kosolapov va Deutsch, 2009). ). Prokariotlarda ko-tarjimaviy buklanish tetik omillar va chaperonlarni o'z ichiga oladi. Eukariotlarda u birinchi navbatda chaperonlar va bog'lovchi oqsillarni o'z ichiga oladi. Masalan, ribosoma tunneli kengaytirilgan konformatsiyalar va peptid zanjirining ikkilamchi tuzilmalarini boshqara oladigan naycha vazifasini bajaradi. Tunnel cheti RNK va ribosoma oqsillaridan iborat. Ushbu oqsillar peptid zanjirining nishonga olinishi va katlanması uchun ishlatiladigan ribosoma bilan bog'liq omillar uchun o'zaro ta'sir qilish joylari. Yangi paydo bo'lgan peptidlarning o'ziga xos qoldiqlari tarjima jarayonini sekinlashtiradi yoki to'xtatadi (Kramer va boshq., 2009). Protein sintezini tartibga solish va Signalni aniqlash zarrasi (SRP) kabi omillarni birlashtirishga yordam beradigan boshqa yo'llar kuzatilgan (Kramer va boshq., 2009). Ribosomalar yangi paydo bo'lgan zanjir va uning tunneldagi holati bilan bog'liq signallarni ularning yuzasiga uzatadi va shu bilan SRP bilan o'zaro ta'sirni nazorat qiladi (Walter and Blobel, 1983 Kramer va boshq., 2009). SRP ning eukaryotlarda paydo bo'lgan oqsil bilan bog'lanishi tarjima jarayonini to'xtatishi mumkin (Kramer va boshq., 2009). Ribosomal arxitektura translatsiyani boshqarish uchun tunnel shovqinlari va oqsil signalizatsiyasi orqali qayta aloqadan foydalanadi (Marin, 2008).

Chaperonlar de-novo oqsillarini katlamada ham ishtirok etadilar. Chaperonlar ularga yaqin joylashgan ribosomalar bilan hamkorlikda ishlaydi. Ushbu hamkorlikdagi tarjima faoliyati vaqtinchalik orkestratsiyani namoyish etadi va odatda katlama jarayonida quyi oqimda harakat qiladi. Ko'p sonli chaperon mexanizmlari va ularning yangi paydo bo'lgan polipeptid zanjirlari bilan vaqtinchalik o'zaro ta'siri uning o'sish bosqichlarida ko-tarjima katlamlarini muvofiqlashtirish uchun harakat qiladi. Bakterial qo'zg'atuvchi omillar ribosoma bilan bog'liq bo'lgan chaperonlardir. Ular yangi paydo bo'lgan zanjirlar va ularning ribosoma chiqish tunnellariga yaqinligi bilan birgalikda ishlaydi. Ribosoma va yangi paydo bo'lgan zanjir bilan tetik omilining o'zaro ta'siri ularning uzunligi, ketma-ketligi va katlama holatiga bog'liq (Kaiser va boshq., 2006 Raine va boshq., 2006). Katlama tezligini kamaytirish orqali in vitro va in vivo, tetik omillari model ko'p domenli substratlarning katlanmasını yaxshilash uchun ko'rsatildi (Agashe va boshq., 2004). Prokaryotlar ribosoma bilan bog'langan chaperon tetiklantiruvchi omillardan foydalanadi. Eukaryotlar J, Hsp70, Hsp 40 kabi omillar va boshqa mexanizmlar bilan bir qatorda yangi paydo bo'lgan zanjir bilan bog'liq kompleks (NAC) oqsilga asoslangan tizimlardan foydalanadi.

Co-TP atrof-muhitning stressiga javoban ham paydo bo'lishi mumkin (Liu va boshq., 2013). To'xtatib turish hujayralarga issiqlik stressi kabi o'zgaruvchan muhit sharoitlariga moslashish imkonini beradi. Ushbu pauza yangi paydo bo'lgan polipeptid ribosomal chiqish tunnelidan chiqqan joyda kuzatilgan. Bu dominant-salbiy mutant yoki boshqa kimyoviy ingibitorlar tomonidan chaperon ishini inhibe qilish ta'siriga ega. Bu cho'zilish va birgalikda TP uchun chaperonlar uchun ikki tomonlama rolni taklif qiladi (Liu va boshq., 2013). Tadqiqotlar shuni ko'rsatdiki, ribosomalar hujayralararo muhitni sezish va reaksiyaga kirishish orqali cho'zilish jarayonini aniq sozlashi mumkin.

Ichki nazorat (nukleotidlar tartibi)

Yangi tug'ilgan oqsillarning TP, shuningdek, mRNKdagi nukleotidlarning joylashuvi, shuningdek, oqsil sintezini beqarorlashtiradigan yoki to'xtatuvchi nukleotid kodlash hududlari bo'limlari bilan bog'liq. Pauza mRNK tuzilishi (Somogyi va boshq., 1993), SRP bilan bog'lanishi (Lipp va boshq., 1987), mRNK bog'lovchi oqsillar, noyob kodonlar (Varenne va boshq., 1984) va anti-Shine-Dalgarno (aSD) tomonidan qo'zg'atilishi mumkin. ) kodon ketma-ketligi (Li va boshq., 2012). Noyob kodonlarni ko'proq kodonlar bilan almashtirish ko'rsatildi Escherichia coli yoki Saccharomyces cerevisiae Proteinlarni tezroq tarjima qilish tezligiga olib keldi. Ammo, bu omillar, shuningdek, ushbu oqsillarning faolligini yomonlashtiradi (Crombie va boshq., 1992 Komar va boshq., 1999). Bu jim mutagenez 20% ga pasaygan o'ziga xos faollikka olib keldi, bu noto'g'ri qatlamlanish darajasini oshiradi. Bundan tashqari, ko'p domenli oqsilning katlama samaradorligi ko'rsatilgan E. coli Noyob kodonlarning ko'p tRNKlar bilan sinonimik almashtirilishi bilan bezovta qilingan (Chjan va boshq., 2009). Biroq, ma'lumotlar shuni ko'rsatadiki, tRNK ning belgilangan darajalari bilan sinonim tarzda kodlangan mRNK lar turli tezliklarda tarjima qilinadi (Sorensen va boshq., 1989 Sorensen va Pedersen, 1991 Li va boshqalar, 2012). Masalan, insonning ABCB1 genidagi jim mutatsion P-glikoproteinda konformatsion o'zgarish sodir bo'lishiga olib keldi. Ushbu oqsil turlicha katlanmış bo'lib, tarjimaning vaqtinchalik o'zgarishi natijasida katlama jarayonining vaqtiga ta'sir qiladi (Kimchi-Sarfaty va boshq., 2007). Shunday qilib, protein katlama yo'llari DNKning kodlash hududlaridagi o'zgarishlarga ta'sir qiladi.

Zarrachalarni mRNK bilan bog'lash misolini kodlash mintaqasi beqarorligi determinanti (CRD) deb nomlanuvchi c-myc mRNKning 249 nukleotid hududida topish mumkin (Lemm va Ross, 2002). CRD mintaqasida paydo bo'lgan TP c-myc mRNKning quyi oqim qismlarini endonukleaza bo'linishiga moyil bo'lishiga olib keladi, deb taxmin qilingan (Lemm va Ross, 2002). Ushbu hujum to'xtash vaqtida sodir bo'lishi mumkin, agar ma'lum bir bog'lovchi oqsillar (CRD-BP) bu hududga uni endonukleaza jarayonidan himoya qilmasa. Pauza joylari CRD c-myc mintaqasida joylashgan va noyob arginin (CGA) va qo'shni treonin (ACA) kodonlari bilan taqqoslanadi (Lemm va Ross, 2002). Lemm ma'lumotlari (Lemm va Ross, 2002) pauza joylari CRD ichidagi turli kodonlarda ham paydo bo'lishini ko'rsatadi. Biroq, birinchi arginin kodoni eng kuchli joydir. Arginin CGA va treonin ACA kodonini keng tarqalgan sinonimik kodonlarga o'zgartirish ribosomaning to'xtatilishiga olib kelmadi. Bu CGA va ACA kodonlari pauza joyi ekanligi haqidagi da'voni qo'llab-quvvatlaydi (Lemm va Ross, 2002), chunki CGA va ACA pauza hosil qiladi, ularni sinonimik kodonlar bilan almashtirish esa pauza ta'sirini yaratmaydi.

Oxirgi ishlar mRNKdagi kodonlarning o'ziga xos joylashuvi va tarjima tezligi o'rtasidagi kuchli bog'liqlikni ko'rsatadigan yuqoridagi kuzatishlar asosida qurilgan (Li va boshq., 2012). Shine Dalgarno (SD) ketma-ketligiga o'xshash kodlash mintaqalaridagi kodon juftlari TP bilan bevosita bog'liqligini ko'rsatdi. Bakteriyalarda tarjima jarayoni boshlanishidan oldin SD ketma-ketligi deb nomlanuvchi olti nukleotidli elementlar ketma-ketligi olinadi. Odatda bu SD ketma-ketligi mRNK transkriptining kodlash hududidan oldin bo'ladi va ribosomaning boshlang'ich kodonida bog'lanishiga imkon beradi (Chen va boshq., 1994). SD ketma-ketligi odatda AUG boshlang'ich kodonining yuqori oqimida joylashgan (Shine va Dalgarno, 1975). Translatsiya tezligi geksanukleotidning ribosomaning 16S rRNKidagi aSD ketma-ketligiga gibridlanishning erkin energiyasining funktsiyasidir. Ushbu bir xil bo'lmagan stavkalar mRNK transkriptida mavjud bo'lgan genetik xabarning kodlash hududlari tanasiga o'rnatilgan kodga (o'xshash aSD ketma-ketliklari shaklida) bog'liq (Li va boshq., 2012). Vaqtinchalik pauzalar cho'zilish jarayonini modulyatsiya qilish orqali yangi paydo bo'lgan oqsilning ko-translatsion katlanishiga ta'sir qilishi ko'rsatilgan (Li va boshq., 2012). Ushbu vaqtinchalik nazorat oqsil funktsiyasini belgilashda katta rol o'ynaydi.

TP hozirgacha juda oz sonli bakterial bo'lmagan turlarda o'rganilgan. Shalgi va boshqalar. (2013) sichqoncha va inson hujayralarida issiqlik zarbasi hodisalari tufayli cho'zilishning to'xtatilishiga olib keladigan TP dalillarini xabar qildi. Sitoplazmada ham, tarjima paytida ham oqsillarning noto'g'ri qatlamlanishi hujayrani issiqlik zarbasi oqsillarining yuqori tartibga solinadigan ifodasini qo'llash orqali javob berishga undaydi. Issiqlik stressi hodisasi paytida TP ko'pchilik sichqoncha va inson hujayralarida 65-kodon atrofida ribosomada boshlanadi. Ushbu genom miqyosidagi hodisa ribosoma bilan bog'liq bo'lgan chaperonlarni o'z ichiga olishi taklif qilingan. Tartibga solish mexanizmlari genning mRNKlarining ko'pchiligining 65-kodonida TPda ishtirok etishi mumkin, bu esa cho'zilish pauzasini keltirib chiqaradi, bunda issiqlik bilan bog'liq noto'g'ri qatlamlarga javob berish uchun ma'lum bir toifadagi chaperonlar qo'llaniladi (Richter va boshq., 2010). Kodonning 65-pozitsiyasidagi kodonlar kodon ortiqchaligi funktsiyasi sifatida vaqtinchalik sozlashni ko'rsatadimi yoki yo'qligini hali ko'rish kerak.

Mexanik va ichki nazorat o'rtasidagi umumiy mavzu

Buklanish jarayonining mexanik bajarilishi (chiqish tunnel/faktorlar/kaperonlar) va yangi paydo bo'lgan oqsilning katlanishida ishtirok etuvchi ichki mRNK jarayonlari o'rtasida umumiy bog'liqlik mavjud. Biz ta'kidlaymizki, ko-translatsion katlamaning sababiy aloqasi mRNK ichidagi kodonlarning belgilangan joylashuvi bilan bog'liq. Biz buni qo'zg'atuvchi omillar uchun chaperonlar va bog'lovchi oqsillarning barchasi yangi aminokislotalar zanjiri ketma-ketligi bilan bog'liqligiga asoslaymiz. Aminokislotalar ketma-ketligi, zaruriy natijaga ko'ra, mRNK ketma-ketligiga ishora qiladi. Bundan tashqari, biz tarjimani to'xtatib turish bilan o'zaro ta'sirlarni mRNKdagi ortiqcha kodonlarning o'ziga xos tartibiga va oxir-oqibat genomga qarab kuzatish mumkin, deb taxmin qilamiz. Biz ribosoma ichidagi mRNK kodonlarini tarjima qilishda pauza holatini yaratish orqali pauza funktsiyalarini osonlashtirishni taklif qilamiz. Bu oqsil omillari, qo'zg'atuvchi omillar va boshqa shaperonlarga katlama operatsiyalarini mexanik ravishda bajarish uchun zarur vaqtni beradi.

“pasalovchi funktsiya” aminokislotalar ketma-ketligiga tunnel-oqsil o'zaro ta'siridan ko'ra, o'ziga xos mRNK kodon ketma-ketligidan kelib chiqadi. Ushbu bahs noyob kodonlarni sinonimik kodonlar bilan almashtirishni o'z ichiga olgan ma'lumotlar bilan qo'llab-quvvatlanadi. E. coli. Agar pauza effekti faqat aminokislotalar zanjiri ketma-ketligi bilan bog'liq bo'lsa, u holda kodonlarni sinonimik kodonlar bilan almashtirish bir xil tarjima tezligi bilan bir xil katlanmış aminokislotalar zanjirini hosil qilishi kerak. Biroq, noyob kodonlarni sinonimik kodonlar bilan almashtirish tezlik va konformatsiya o'zgarishlarida o'zgarishlarga olib keldi (Gong va Yanofsky, 2002 Lemm va Ross, 2002 Chiba va boshqalar, 2011 Li va boshq., 2012).

Bakteriyalarning global tahlili shuni ko'rsatadiki, kuchli pauzalarning 70% kodlash hududlarida ichki SD-ga o'xshash ketma-ketliklar hukmron bo'lganda sodir bo'ladi (Li va boshq., 2012). Shuni ta'kidlash kerakki, kodlash hududlari tanasidagi kanonik SD saytlari o'zgaruvchan paydo bo'lish tezligiga ega bo'lgan past yaqinlikdagi heksamerlardan farqli o'laroq kam uchraydi. Bu mantiq TP sababligi kodon ketma-ketligiga bog'liq degan gipoteza bilan mos keladi, natijada uni genomga qaytarish mumkin. Ushbu sabab va ta'sir munosabatlari TP hodisasining sababini izchil tushuntirishni ta'minlaydi.

Ushbu fikrdan foydalanib, biz ribosoma ichidagi translatsiyani to'xtatib turadigan mRNKdagi SD ketma-ketliklarini ko'rib chiqdik. Biz ushbu hodisani genetik kodning o'ziga xos ortiqchaligi bilan kod ishtirok etganligini aniqlash uchun ko'rib chiqdik. Biz ushbu ma'lumotlarni batafsil ko'rib chiqdik va u oqsillarni yig'ish uchun ishlatiladigan kodning xususiyatlarini namoyish etishini ko'rsatamiz. Biz ushbu kod bir xil ontologik ko'rsatma ma'lumotlarida joylashganligini ko'rsatamiz (PIo) oqsil sintezi jarayonida ishlatiladigan genetik kod sifatida makon. Genlarning kodlash hududlarida bir xil kodning ikki tomonlama ishlatilishi, agar har bir kodon o'ziga tegishli aminokislota bilan faqat bitta xaritaga ega bo'lsa, semiotik tarzda boshqariladi. Biroq, genetik kod ortiqcha ekanligi ma'lum, ya'ni bir nechta kodonlar bir xil aminokislotalarni buyurishi mumkin. Biz shuni ko'rsatamizki, aynan shu ortiqchalik genetik kodning ikki tomonlama funksionalligi bir xil kodlash maydonida bir vaqtning o'zida funktsiyalarni kodlash va bir xil nukleotidlar qatoridan noaniqliksiz foydalanish imkonini beradi. Bunda biz �generacy” atamasi nima uchun mutlaqo noo'rin ekanligini ko'rsatamiz. The dual coding functionality of redundancy is anything but �generate.” It represents, instead, far more sophistication, layers, and dimensions of formal prescription.

We posit that the translation pausing function is enabled by a code that is superimposed upon the genetic code, yet remains distinct and independent from the genetic code. We further posit that the genetic code consist of multi-threads of information co-existing in the same physical space which is made possible by the redundancy of the genetic code itself. To support these propositions we begin by examining the data for aSD hexamer sequences to determine the logic and rules that give it the property of code.


Genetic code redundancy and its influence on the encoded polypeptides

The genetic code is said to be redundant in that the same amino acid residue can be encoded by multiple, so-called synonymous, codons. If all properties of synonymous codons were entirely equivalent, one would expect that they would be equally distributed along protein coding sequences. However, many studies over the last three decades have demonstrated that their distribution is not entirely random. It has been postulated that certain codons may be translated by the ribosome faster than others and thus their non-random distribution dictates how fast the ribosome moves along particular segments of the mRNA. The reasons behind such segmental variability in the rates of protein synthesis, and thus polypeptide emergence from the ribosome, have been explored by theoretical and experimental approaches. Predictions of the relative rates at which particular codons are translated and their impact on the nascent chain have not arrived at unequivocal conclusions. This is probably due, at least in part, to variation in the basis for classification of codons as "fast" or "slow", as well as variability in the number and types of genes and proteins analyzed. Recent methodological advances have allowed nucleotide-resolution studies of ribosome residency times in entire transcriptomes, which confirm the non-uniform movement of ribosomes along mRNAs and shed light on the actual determinants of rate control. Moreover, experiments have begun to emerge that systematically examine the influence of variations in ribosomal movement and the fate of the emerging polypeptide chain.


Ma'lumotnomalar

Amoeba Sisters. (2019, September 17). How to read a codon chart. YouTube. https://www.youtube.com/watch?v=LsEYgwuP6ko&feature=youtu.be

Bozeman Science. (2012, September 15). Comparing DNA sequences. YouTube. https://www.youtube.com/watch?v=OSKwuOccAak&feature=youtu.be

Wikipedia contributors. (2020, July 2). Marshall Warren Nirenberg. In Vikipediya. https://en.wikipedia.org/w/index.php?title=Marshall_Warren_Nirenberg&oldid=965562106

The smallest unit of life, consisting of at least a membrane, cytoplasm, and genetic material.

A nucleic acid of which many different kinds are now known, including messenger RNA, transfer RNA and ribosomal RNA.

A sequence of 3 DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis.

Aminokislotalar organik birikmalar bo'lib, oqsillarni hosil qiladi.

The specific location in DNA where a set of codons will code for a certain protein. The reading frame begins with the start codon (AUG).

Deoxyribonucleic acid - the molecule carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses.

A large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression.


Tarkib

There are many theories behind the origin of genetic codes. The genetic code used by all known forms of life is nearly universal. However, there are a huge number of possible genetic codes. If amino acids are randomly associated with triplet codons, there will be 1.5 x 10 84 possible genetic codes. Phylogenetic analysis of transfer RNA suggests that tRNA molecules evolved before the present set of aminoacyl-tRNA synthetases.

Theoretically the genetic code could be completely random (a "frozen accident"), completely non-random (optimal) or a combination of random and nonrandom. There are sufficient data to refute the first possibility. For a start, a quick view on the table of the genetic code already shows a clustering of amino acid assignments. Furthermore, amino acids that share the same biosynthetic pathway tend to have the same first base in their codons, and amino acids with similar physical properties tend to have similar codons.

There are four themes running through the many theories that seek to explain the evolution of the genetic code (and hence the origin of these patterns):

1. Chemical principles govern specific RNA interaction with amino acids. Aptamer experiments showed that some amino acids have a selective chemical affinity for the base triplets that code for them. Recent experiments show that of the 8 amino acids tested, 6 show some RNA triplet-amino acid association. This has been called the stereochemical code. The stereochemical code could have created an ancient core of assignments. The current complex translation mechanism involving tRNA and associated enzymes may be a later development, and that originally, protein sequences were directly templated on base sequences.

2. Biosynthetic expansion. The standard modern genetic code grew from a simpler earlier code through a process of "biosynthetic expansion". Here the idea is that primordial life "discovered" new amino acids (e.g., as by-products of metabolism) and later back-incorporated some of these into the machinery of genetic coding. Although much circumstantial evidence has been found to suggest that fewer different amino acids were used in the past than today, precise and detailed hypotheses about exactly which amino acids entered the code in exactly what order have proved far more controversial.

3. Natural selection has led to codon assignments of the genetic code that minimize the effects of mutations. A recent hypothesis suggests that the triplet code was derived from codes that used longer than triplet codons. Longer than triplet decoding has higher degree of codon redundancy and is more error resistant than the triplet decoding. This feature could allow accurate decoding in the absence of highly complex translational machinery such as the ribosome.

4. Information channels: Information-theoretic approaches see the genetic code as an error-prone information channel. The inherent noise (i.e. errors) in the channel poses the organism with a fundamental question: how to construct a genetic code that can withstand the impact of noise while accurately and efficiently translating information? These “rate-distortion” models suggest that the genetic code originated as a result of the interplay of the three conflicting evolutionary forces: the needs for diverse amino-acids, for error-tolerance and for minimal cost of resources. The code emerges at a coding transition when the mapping of codons to amino-acids becomes nonrandom. The emergence of the code is governed by the topology defined by the probable errors and is related to the map coloring problem.

Ribonucleic acid (RNA) with two repeating units (UCUCUCU → UCU CUC UCU) produced two alternating amino acids. This, combined with the Nirenberg and Leder experiment, showed that UCU codes for Serine and CUC codes for Leucine. RNAs with three repeating units (UACUACUA → UAC UAC UAC, or ACU ACU ACU, or CUA CUA CUA) produced three different strings of amino acids. RNAs with four repeating units including UAG, UAA, or UGA, produced only dipeptides and tripeptides thus revealing that UAG, UAA and UGA are stop codons. With this, Khorana and his team had established that the mother of all codes, the biological language common to all living organisms, is spelled out in three-letter words: each set of three nucleotides codes for a specific amino acid. Their Nobel lecture was delivered on December 12, 1968. To do this Khorana was also the first to synthesize oligonucleotides, that is, strings of nucleotides.

The table of Genetic Code Edit

2nd base
T C A G
1st base T TTT (Phe/F) Phenylalanine TCT (Ser/S) Serine TAT (Tyr/Y) Tyrosine TGT (Cys/C) Cysteine
TTC (Phe/F) Phenylalanine TCC (Ser/S) Serine TAC (Tyr/Y) Tyrosine TGC (Cys/C) Cysteine
TTA (Leu/L) Leucine TCA (Ser/S) Serine TAA Ochre (Stop) TGA Opal (Stop)
TTG (Leu/L) Leucine TCG (Ser/S) Serine TAG Amber (Stop) TGG (Trp/W) Tryptophan
C CTT (Leu/L) Leucine CCT (Pro/P) Proline CAT (His/H) Histidine CGT (Arg/R) Arginine
CTC (Leu/L) Leucine CCC (Pro/P) Proline CAC (His/H) Histidine CGC (Arg/R) Arginine
CTA (Leu/L) Leucine CCA (Pro/P) Proline CAA (Gln/Q) Glutamine CGA (Arg/R) Arginine
CTG (Leu/L) Leucine CCG (Pro/P) Proline CAG (Gln/Q) Glutamine CGG (Arg/R) Arginine
A ATT (Ile/I) Isoleucine ACT (Thr/T) Threonine AAT (Asn/N) Asparagine AGT (Ser/S) Serine
ATC (Ile/I) Isoleucine ACC (Thr/T) Threonine AAC (Asn/N) Asparagine AGC (Ser/S) Serine
ATA (Ile/I) Isoleucine ACA (Thr/T) Threonine AAA (Lys/K) Lysine AGA (Arg/R) Arginine
ATG (Met/M) Methionine ACG (Thr/T) Threonine AAG (Lys/K) Lysine AGG (Arg/R) Arginine
G GTT (Val/V) Valine GCT (Ala/A) Alanine GAT (Asp/D) Aspartic acid GGT (Gly/G) Glycine
GTC (Val/V) Valine GCC (Ala/A) Alanine GAC (Asp/D) Aspartic acid GGC (Gly/G) Glycine
GTA (Val/V) Valine GCA (Ala/A) Alanine GAA (Glu/E) Glutamic acid GGA (Gly/G) Glycine
GTG (Val/V) Valine GCG (Ala/A) Alanine GAG (Glu/E) Glutamic acid GGG (Gly/G) Glycine
nonpolar qutbli Asosiy kislotali (stop codon)

Degeneracy is the redundancy of the genetic code. The genetic code has redundancy but no ambiguity ( above for the full correlation). For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example the amino acid glutamic acid is specified by GAA and GAG codons (difference in the third position), the amino acid leucine is specified by UUA, UUG, CUU, CUC, CUA, CUG codons (difference in the first or third position), while the amino acid serine is specified by UCA, UCG, UCC, UCU, AGU, AGC (difference in the first, second or third position).

A position of a codon is said to be a fourfold degenerate site if any nucleotide at this position specifies the same amino acid. For example, the third position of the glycine codons (GGA, GGG, GGC, GGU) is a fourfold degenerate site, because all nucleotide substitutions at this site are synonymous i.e., they do not change the amino acid. Only the third positions of some codons may be fourfold degenerate. A position of a codon is said to be a twofold degenerate site if only two of four possible nucleotides at this position specify the same amino acid. For example, the third position of the glutamic acid codons (GAA, GAG) is a twofold degenerate site. In twofold degenerate sites, the equivalent nucleotides are always either two purines (A/G) or two pyrimidines (C/U), so only transversional substitutions (purine to pyrimidine or pyrimidine to purine) in twofold degenerate sites are nonsynonymous.

A position of a codon is said to be a non-degenerate site if any mutation at this position results in amino acid substitution. There is only one threefold degenerate site where changing to three of the four nucleotides may have no effect on the amino acid (depending on what it is changed to), while changing to the fourth possible nucleotide always results in an amino acid substitution. This is the third position of an isoleucine codon: AUU, AUC, or AUA all encode isoleucine, but AUG encodes methionine. In computation this position is often treated as a twofold degenerate site.

There are three amino acids encoded by six different codons: serine, leucine, and arginine. Only two amino acids are specified by a single codon. One of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of translation the other is tryptophan, specified by the codon UGG. The degeneracy of the genetic code is what accounts for the existence of synonymous mutations.

Degeneracy results because there are more codons than encodable amino acids. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required (20 amino acids plus stop), and the next largest number of bases is three, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.

These properties of the genetic code make it more fault-tolerant for point mutations. For example, in theory, fourfold degenerate codons can tolerate any point mutation at the third position, although codon usage bias restricts this in practice in many organisms twofold degenerate codons can tolerate one out of the three possible point mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at twofold degenerate sites adds a further fault-tolerance.

Despite the redundancy of the genetic code, single point mutations can still cause dysfunctional proteins. For example, a mutated hemoglobin gene causes sickle-cell disease. In the mutant hemoglobin a hydrophilic glutamate (Glu) is substituted by the hydrophobic valine (Val), that is, GAA or GAG becomes GUA or GUG. The substitution of glutamate by valine reduces the solubility of Beta globulins|β-globin which causes hemoglobin to form linear polymers linked by the hydrophobic interaction between the valine groups, causing sickle-cell deformation of erythrocytes. Sickle-cell disease is generally not caused by a de novo mutatsiya. Rather it is selected for in geographic regions where malaria is common (in a way similar to thalassemia), as heterozygous people have some resistance to the malarial Plazmodiy parasite (heterozygote advantage). [5]

These variable codes for amino acids are allowed because of modified bases in the first base of the anticodon of the tRNA, and the base-pair formed is called a wobble base pair. The modified bases include inosine and the Non-Watson-Crick U-G basepair. [6]

Initiation or Start Codon Edit

The start codon is generally defined as the point, sequence, at which a ribosome begins to translate a sequence of RNA into amino acids. When an RNA transcript is "read" from the 5' carbon to the 3' carbon by the ribosome the start codon is the first codon on which the tRNA bound to Met, methionine, and ribosomal subunits attach. ATG and AUG denote sequences of DNA and RNA, respectively, that are the start codon or initiation codon encoding the amino acid methionine (Met) in eukaryotes and a modified Met (fMet) in prokaryotes. The principle called the Central dogma of molecular biology describes the process of translation of a gene to a protein. Specific sequences of DNA act as a template to synthesize mRNA in a process termed "transcription" in the nucleus. This mRNA is exported from the nucleus into the cytoplasm of the cell and acts as a template to synthesize protein in a process called "translation." Three nucleotide bases specify one amino acid in the genetic code, a mapping encoded in the tRNA of the organism. The first three bases of the coding sequence (CDS) of mRNA to be translated into protein are called a start codon or initiation codon. The start codon is almost always preceded by an untranslated region 5' UTR. The start codon is typically AUG (or ATG in DNA this also encodes methionine). Very rarely in higher organisms (eukaryotes) are non AUG start codons used. In addition to AUG, alternative start codons, mainly GUG va UUG are used in prokaryotes. For example E. coli uses 83% ATG (AUG), 14% GTG (GUG), 3% TTG (UUG) and one or two others (e.g., ATT and CTG).

Termination or Stop codon Edit

In the genetic code, a stop codon (also known as termination codon) is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based upon polypeptides, which are unique sequences of amino acids and most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein — stop codons signal the termination of this process, releasing the amino acid chain.

Stop codons were historically given many different names, as they each corresponded to a distinct class of mutants that all behaved in a similar manner. These mutants were first isolated within bacteriophages (T4 and lambda), viruses that infect the bacteria Escherichia coli. Mutations in viral genes weakened their infectious ability, sometimes creating viruses that were able to infect and grow within only certain varieties of E coli.

1. Amber mutations were the first set of nonsense mutations to be discovered. They were isolated by Richard Epstein and Charles Steinberg, but named after their friend Harris Bernstein (see Edgar pgs. 580-581 [7] ) for the story behind this incident)

Viruses with amber mutations are characterized by their ability to infect only certain strains of bacteria, known as amber suppressors. These bacteria carry their own mutation that allow a recovery of function in the mutant viruses. For example, a mutation in the tRNA that recognizes the amber stop codon allows translation to "read through" the codon and produce full-length protein, thereby recovering the normal form of the protein and "suppressing" the amber mutation. Thus, amber mutants are an entire class of virus mutants that can grow in bacteria that contain amber suppressor mutations.

2.Ochre Ochre mutation was the second stop codon mutation to be discovered. Given a color name to match the name of amber mutants, ochre mutant viruses had a similar property in that they recovered infectious ability within certain suppressor strains of bacteria. The set of ochre suppressors was distinct from amber suppressors, so ochre mutants were inferred to correspond to a different nucleotide triplet. Through a series of mutation experiments comparing these mutants with each other and other known amino acid codons, Sydney Brenner concluded that the amber and ochre mutations corresponded to the nucleotide triplets "UAG" and "UAA". [8]

3. Opal mutations or umber mutations the third and last stop codon in the standard genetic code was discovered soon after, corresponding to the nucleotide triplet "UGA". Nonsense mutations that created this premature stop codon were later called opal mutations or umber mutations.

In RNA: UAG ("amber") UAA ("ochre") UGA ("opal")

In DNA: TAG ("amber") TAA ("ochre") TGA ("opal" or "umber").

Exceptions to the Universal Genetic Code (UGC) in mitochondria
Organizm Codon Standart Roman
Sutemizuvchilar AGA, AGG Arginin Stop codon
AUA Izoleysin Metionin
UGA Stop codon Triptofan
Umurtqasizlar AGA, AGG Arginin Serin
AUA Izoleysin Metionin
UGA Stop codon Triptofan
Xamirturush AUA Izoleysin Metionin
UGA Stop codon Triptofan
CUA Leysin Treonin

Exceptions to the genetic code: Although the vast majority of living organisms today use the standard genetic code, geneticists have discovered a few variations on this code. Moreover, these variants are found in different evolutionary lineages and consist of different translations of a few codons.

The CUG codon, usually translated as leucine , corresponds to the serine 2 in many species of fungi Candida 3 .

Many species of green algae of the genus Acetabularia use stop codons UAG and UAA to encode glycine .

Many ciliates like Paramecium tetraurelia , Tetrahymena thermophila or Stylonychia 4 lemnae use codons UAG and UAA to code for glutamine instead of stop. UGA is the one stop codon used by these cells.

The ciliate Euplotes octocarinatus uses the codon UGA to encode cysteine, leaving UAG and UAA as stop signs.

In the three kingdoms of life , we sometimes find a twenty-first amino acid, selenocysteine , encoded by the UGA codon (normally a stop codon).

In archaea and eubacteria , a twenty-second amino acid, pyrrolysine is sometimes met, encoded by UAG (also usually a stop codon).

The first amino acid incorporated (determined by the start codon AUG) is a methionine in most eukaryotes , more rarely a valine (in some eukaryotes ), and formyl-methionine in most prokaryotes . In addition, this codon is GUG or GUU sometimes in some prokaryotes.

We therefore believe that life today originally had a smaller number of amino acids. These amino acids have been modified and have seen their numbers increase (by a phenomenon similar to the formation of sélénocytéine and pyrrolysine derived from serine and lysine, respectively, modified as they are on their transfer RNA on the ribosome .) These new amino acids were then used a subset of transfer RNAs and their associated coding. Maybe we notice signs of this phenomenon with glutamine , which in some bacteria, derived from glutamate still attached to its tRNA.

Another exception: the code is sometimes ambiguous. For example, the codon UGA is in the same organism ( Escherichia coli , for example) sometimes code for the 21st amino acid mentioned above ( selenocysteine ) or "stop".


Videoni tomosha qiling: Cellen del 2 (Iyul 2022).


Izohlar:

  1. Lavan

    Aytish mumkinki, bu :) qoidalardan istisno

  2. Mizuru

    Bu to'g'ri! I think this is a good idea.

  3. Kigabei

    Menimcha, siz xato qilyapsiz. Men o'z pozitsiyamni himoya qila olaman. Menga PM orqali elektron pochta xabarini yuboring.



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