підручники. біохімія / Uchebnik_po_Biokhimii_E_S_Severin

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LJ:JT5I reHa reMorno611Ha cKopocTh 1aMemeHttH o.n:- Horo OCHOBamrn .n:pymM JTe)!(HT B HHTepBaJTe µ =

2,5xl0-9-5xI0-9 3aMeH B raMeTe 3a 01IHO IIOKOJieHI1e. lfro6h1 npe.n:cTaBHTh ce6e, '-ITO 01Ha'-!a10T3Tl1 UI1cppbr, pacnpOCTJJaHHM 3TY CKOpOCTh Myrauttti Ha Bech reHOM '-leJTOBeKa - 3xl09 nap OCHOBaHI1H. YMHO)!(HB pa1Mep reHOMa Ha cKopocTh µ, Mhr no- JTY'-IHM, '-!TOreHOM 3a 01IHO nOKOJTeHHe MO)J(eT no- JIY'-II1ThOT 7 1IO 15 Myrau11i1, T.e. 3TO 3Ha'-!I1T, '-!TO Ka.IK.ll,aH raMeTa conep)J(HT TaKOe KOJTI1'-leCTBOI13Me- HeHI1H B )],HK no cpaBHeHI1lO c pO,IIHTeJTbCKOH )],HK.

A nocKOJTbKY y Ka.IK.ll,Oro I1H1Il1BI1.llYYMa KJTeTKM .n:11nJTOl11IHhI 11 ITOJTY'-la!OTCH nptt CJTI151HI1I1 2 raMeT'TO Myrau11i1 TO)J(e B 2 pa3a 6oJThwe.

CrrpaumBaeTCH, KaKMM )J(e 06pa10M YeJToBe'-!e- crno cnpaBJT5JeTC51 c TaKOH MyraUHOHHOH Harpy3Koii? Orneqa51 Ha 3TOT Bonpoc, CJTenyeT rroMHHTh, '-!TOKO.lll1PYIOIU11e '-!aCTH reHOB, 113MeHeHH51 B KOTOpbIX Hatt6oJTee orrncHbI, 1aHttMa10T He 6oJTee I 0% reHOMa. CJ1TyaUI151 o6JTeryaeTC51 eme I1 TeM, '-!TO )laTieKo He Ka.1K.UaH Myrawrn B Ko.n:11py10urei1 06JTaCT11 11MeeT cpeHOTHITH'-lecKoe rrpoHBJTeHtte. MHortte rrona,IIaIOT B 3'-nOJTO)J(eHtteK01IOHOB 11, TaKMM o6pa30M, 51BJ15llOTC51 «MOJT'-laIUHMH», TaK KaK 6JTaro)lapH Bhip0)K)leHHOCTI1 retieTI1'-!eCKOroKO)la OHH He rrpl1BO.ll51T K aMHHOKl1CJTOTHhIM 3aMeHaM, .llPYr11e oKa3bIBaIOTCH B JlOMeHax, HecymecTBeHHbIX LJ:JTH cpyHKUHOHHpOBaHHYI 6e.TIKOB. IloTOMCTBy nepenalOTCH MyTaU11I1, rrpOI1CXOJl51W11e B raMeTax, a I1X npoueHT COBCeM HeBeJTHK.

B. 0PrAHM3AUMH rEHOMA qEJioBEKA

feHOM 3yKapttOTl1'-leCKMXKJTeTOK (KJTeTOK '-!eJTO- BeKa B '-!aCTHOCTl1) conep)!(HT 3Ha'-IHTeJibHO 60JThwe Ll,HK, '-!eMreHOM np0Kap110TOB. y KHllle'-IHOH naJTO'-IKl1 E. coli )],HK conep)(rnT 3,8xl06 nap HYKJTeOTl1LIOB 11JII1 OKOJTO 3000 reHOB. IlpH 3TOM BC51 ,IJ,HK BbITIOJ1H51eT onpeneJTeHHbre cpyttKUHH: KOLJ:H- pyeT 6eJTKH, pPH K, TPHK HJIH yqacrnyeT B peryJlHUHH o6pa3oBamrn reHHblX rrponyKTOB. 06maH LJ:JTttHa ,IJ,H K railJTOH)lHoro Ha6opa 113 23 xpoMocoM lfeJioBeKa cocrnrurneT 3,5xl09 nap HyKJTeon1-

LIOB, '-!TOB 1000 pa3 rrpeBOCXO)ll1T pa3Mep reHOMa npoKapttOTOB. 3Toro KOJII1'-!ecTBa)],HK 11,0CTaTO'-l- HO 1IJ151 C031IaHmr HeCKOJlhKHX Ml1JTJTI10HOB reHOB. 011,HaKo, cornacHO MHOfHM He3aBI1Cl1MhIM Il011,C'-!e-

TaM, HCTHHHoe 'IHCJIO CTPYKTYPHbIX reHoB Haxo1IHTCH B o6JTaCTI1 l 00 000, a no .n:attHbIM Me)J()lyttapo.n:ttoro KOHCOPUttyMa H cpHpMbl «Uenepa feHoMHKC», IlOJiylfeHHhIM nptt ceKBeH11poBaH1111 reHOMa '-!eJTOBeKaH ony6JIHKOBaHHbIM B 2001 r., '-111CJIO6e- JIOK-KO)ll1PYlOIUI1X reHOB, no oueHKaM nepBOH opraHH3aUH11, COCTaBJTHeT 31780, a ITO oueHKaM BTOpo:H - 39 114 reHoB. nocJJe.IJ:OBaTeJTbHOCTb HYKJJeOTH1IOB B Ll,HK '-leJJOBeKa11MeeT o6JJaCTI1, K01Il1PYlOIUI1e 6eJIKl1 (He 6onee 2% o6urero rettoMa), o6nacTtt, KO.llHPYlOIUtte PHK (OKOJTO 20% reHoMa), H noBTOp51lOIUI1eC51 IIOCJTe11,0BaTeJTbHOCTH (60JTee 50% o6urero reHoMa).

Cl>yHKUI111 «l136hITO'-IHOH» )],HK 1IO KOHUa He HCHhl, ITOJlaralOT, lfTO OHa yYacrnyeT B peryJT51U1111 3Kcrrpecc1111 reHOB, rrpoueccttHra PHK, BbITIOJIHYIeT CTPYKTYPHhle cpyHKUHH, noBbilllaeT TO'-IHOCTb roMOJJOftt'-!Horocnap11Battl15l 11 peKoM611ttau1111 xpoMOCOM B rrpouecce Mei101a, cnoco6crnyeT ycrrelllHOH penJIHKau,1111. nOJiblllaH '-!aCTh3Toi1 ,IJ,H K B03HHKJTa B pe1yJihTaTe o6paTHOii TJJaHcKpttnUHH PHK l1 6JJaronap51 HaJTI1'-II1lOI101IBH)J(HbJX 3JTeMeHTOB.

11aCTO DOBTOPHIOIIIHeCB DOCJie11,0BaTeJihHOCTH

)],HK

Bo cppaKUHH «tt36bITO'-IHOi1» Ll,HK Bhf1Iemrt0T oTHOCttTeJJhHO KOpOTKHe nocJTe)J,OBaTeJTbHOCTH 1IJ1l1HOH OT 2 1IO I 0 nap HYKJTeOTH1IOB, rroBTop.s:nom11ecH Ml1JTJll10Hbl pa3. 3TH '-!aCTO I10BTOpHIDIUHeC51 ITOCJTe)loBaTeJlbHOCTl1 ITOJTY'-IHJTH Ha3Bam1e «CaTeJTJTHTHOH )],HK». 0HH COCTaBJ151lOT OKOJTO I0% BCero reHoMa '-!eJJoBeKa,pacceHHbI no sceMy reHeTHqecKOMY MaTep11any IGieTKH, HO npe11MymecrneHHO JIOKaJTH3YfOTC51 B ueHTpOMepHblX H TeJTOMepHbIX 06JTacrnx 60JTbllll1HCTBa xpOMOCOM.

YMepenno nOBTOpBIOlll,Hecs noc~enoeaTe~bHOCTH

)lHK

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6bIJIH o6Hapy)KeHbl nocJie,!lOBaTeJibHOCTH )],HK L(JIHHOM npttMepHO B 300 nap H)'K.JleOTHL(OB,KOTOpble nOBTOPHIOTCH OKOJIO MHJIJIHOHa pa3 (B cpe)J,- HeM qepe3 Ka)KL(hie 5000 nap H)'K.JleOTHL(OB)H pacceHHhI IIO BCeMy reHOMy qeJIOBeKa.

qaCThie npe,!lCTaBHTeJIH yMepeHHO noBTOPHIOlll,HXCH nocJie,!lOBaTeJibHOCTeM - line-ceMeMCTBO

(oT aHrn. long interspersed elements), HJIH ceMeM:-

CTBO L(JIHHHhIX pacceHHHhIX 3JieMeHTOB, B KOTOpoe BXO,!lHT )],HK IIOCJie)J,OBaTeJibHOCTH )J,JIHHOM OT

5000-8000 nap HYKJieOTH,!lOB, BCTpe'IaIOTCHB reHOMe B KOJIH'Iecrne850 000 KOnHM.

YuuKam.Hh1e nocJie)J,oeaTeJii.uocTn )],HK

0HH rrpe,!lCTaBJieHhl Ll,HK-rrocJie,!lOBaTeJibHOCTH- MH, KOTOpbie IIPHCYTCTBYIOT B feHOMe B KOJIH'Iecrne O,!lHOM HJIH HeCKOJibKHX KOIIHM, H TpaHCKpH6ttpyIOTCH, o6pa3yH MPHK, co):(ep)Kalll,He ttHcpopMallmo o pa3.Jllf4HhIX 6eJIKax (pttc. 4-58).

THIIWIHhlH reH qeJIOBeKa COCTOHT npH:Meptto H3

28 000 HyKJieOTHL(OB H CO)J,ep)KHT B cpe)J,HeM 8 3K30HOB, ero KOL(HPYIOlll.aH nocJie,!lOBaTeJibHOCTh coCTaBJIHeT OKOJIO 1340 nap HyKJieOTHL(OB H umcppy-

eT 6eJIOK, BKJIIO'IaIOlll,HH 447 aMHHOKHCJIOTHhIX ocrnTKOB. CaMhiti KpyrrHhiti reH - reH Mhlllle'IHOro 6eJIKa )J,HCTpOcpHHa, COCTOHlll,HM H3 H)'K.JleOTH)J,OB,a HaH60Jiblllee KOJIH'IeCTBO3K30HOB

(234) rrpHCYTCTByeT B reHe cp116pHJIJIHpHOfO 6eJIKa THTHHa, OTBeTCTBeHHOfO 3a naCCHBHYIO 3JiaCTH4HOCTh CKeJieTHhlX MhlllIU.

HepenKo yHHKaJihHhie rrocJie,!lOBaTeJihHOCTH o6pa3yIOT MYJILTHreuui.1e ceMeiicTea, pacrronaraIOlll.HecH B BH,!le KJiacTepoB B orrpe,!lenetttthIX 06nacTHX 0,IIHOM HJIH HeCKOJibKHX xpoMOCOM. TipHMepaMH MYJihT.HreHHhIX ceMeMCTB MOfYT CJIY)KHTh

reHbl pH60COMaJibHhIX, TpaHCIIOPTHhlX H MaJihIX HL(eptthIX PHK, reHhI a- H ~-rno611HoB, Ty6ynH-

HOB, MHOrJI06.HHa, aKTHHa, Tpattccpepirna H MHOfHX L(pymx.

B MYJihTttreHHhIX ceMeticrnax ttapHL(Y c cpyttKUHOHaJihHO aKTHBHhIMH reHaMH CO)J,ep)KaTCH ncee- )J,OreHbl - MYTaUHOHHO H3MeHeHHhie rrocJie)J,oBaTeJihHOCTH, He cnoco6Hble TpaHCKpH6HpoBaThCH HJIH npOL(yUHPYIOlll.He cpyHKUHOHaJihHO tteaKTHB'- Hhie reHHbie npoL(yKThl.

OceB)J,OfeHhl - O,IJ,Ha ll3 Ba.JKHhlX CT()YJ<TYPHhlX oco6eHHOCTeH reHOMa qeJIOBeKa. 3TH yttHKaJihHhie IIOCJie.UOBaTeJibHOCTll oqeHh CXO)J,Hhl no CTp)'Kzype c orrpe.ueJieHHhIMtt reHaMtt. B CB513H c TeM, qTo s reHHhIX ceMeHCTBax Hap51,11,y c rrceB,IJ,OfeHaMH coxpaH51lOTC51 Hett:3MetteHHhie reHhI, )Kl13Hecrroco6HOCTh opraHH3Ma He HapywaeTC51. ,l1.JI51 MHOfllX reHoB o6Hap)')KeHhI rrces,IJ,oreHhI. Mx KOJirrqecrno sapbtt:pyeT OT O)J,HOH llO HeCKOJihKHX ,IJ,eC51TKOB KOIIHH Ha reHOM, 11, KaK rrpaBl1JIO, OHH pacrrOJIO)!(e- Hhl TaHlleMHO. MHoma rrces,IJ,oreHhI 11 coorneTcrnyJOIUHe HM HOpMaJihHhTe reHhI JIOKaJil130BaHhl B pa3HhlX xpOMOCOMax.

B. IlOJIUMOP<l>ll3M EF.JIKOB

00CKOJihKY 60JihWl1HCTBO HOpMaJihHhIX KJieTOK qeJIOBeKa lll1IIJIOH:llHhl, TO OHM C0,!1,ep)KaT )],Be KOnlltt KillK,Ll,OH xpOMOCOMhI, OllHa 113 KOTOpbIX rronyqeHa OT oma, a BT0pa51 OT MaTep11. 3Ttt )],Be KOIIIDI OllHOH ll TOH. )Ke xpoMOCOMhI Ha3hIBaJOT roMOJIOIWIHhTMM (p:ttc.

B ,UHK Ka.JKII.Oif. xpoMOCOMhr co,IJ,ep)KITTC51 6o-

Jiee ThlC5Jq:tt reHOB. CoorneTCTBYJOIUl1e llPYf llPYfY reHhI B fOMOJIOf:ttqttbIX xpOMOCOMax Ha3bIBaIOT aJIJieJI51Ml1. A.lmeJIH: MOryr 6hITh M.D:eHTiflIHhIM:tt l1 C0,!1,ep)J<aT O)UiHaKOBYJO rrocJie.uosaTeJihHOCTh ttyKJieOTMllOB. B 3TOM cnyqae mwmJ1llYYM, HMeJOIU:ttif. TaKMe aJIJieJI:tt, 6y,IJ,eT fOM03HrOTeu no ,IJ,aHHOMY nptt3HaKy. EcJitt aJIJieJitt pa3.JIWiaIOTC51 no noCJie,IJ,OBaTeJibHOCrn ttyKJieOTM.D:OB B ,UHK, TO fOBOpSIT 0 rerep03HfOTHOM HaCJie)lOBaHHH reHa. B 3TOM cnyqae l1HllHBJ1llYYM 6y,IJ,eT HMeTu 2 6eJI-

KOBhIX npo,IJ,yKTa reHa, pa3JI:ttqaJOIUH:XC51 no aMHHoKHCJIOTHoti nocJie)J,OBaTeJihHOCTH.

y Ka)K)J,OfO qeJIOBeKa cymecrnyeT TOJihKO 2 pa3HhlX aJIJieJI51 OllHOro reHa, TOr,IJ,a KaK B nonyAAu1111 JIJOLJ,eH sapHaHTOB aJIJieJieH MO)KeT 6bITh orpOMHOe MHO)KeCTBO. KaK )')Ke rosop11JIOCh paHee, H3MeHqrrsocTh CT())'KTYPhl,UHK, a CJie)l,OBaTeJibHO pa3HOo6pa3tte aJIJieJieti, o6ycJIOBJieHo MYTaUHOHHhIM npoueccoM ll peKOM6tt:HaUH51Mll B fOMOJIOfllqHhIX xpoMocoMax noJIOBhIX KJieTOK. EcJIH s xone Mei103a peKoM611Hau1111 conposo)K)l,aJOTC51 o6MeHoM yqacTKaMtt ,UHK, MeHhIIIHMll no pa3Mepy, ':leM reH, TO TaKOH npouecc MO)KeT nptt:BOllllTh K II051BJieHmo HOBhIX, npe)!(Ll;e He cymecTBOBaBIIIHX aJIJieJieH.

A rrocKOJihKY peKoM6tt:Hau:11:11 - 6oJiee qacThie co6bITH:51, qeM MYTau1111 B KOMPYJOIUH:X yqacTKax retta, TO pa3ttoo6pa3rre saprraHTOB aJIJieJieif. o6ycJioBJietto rnaBHhIM o6pa30M HMM.

CymecrnoBaHHe B nonyJI5IUHH 2 H 6oJihIIIero qttcJia aJIJieJieH OllHOfO retta Ha3hIBaIOT «aJIJieJIOMOixl>H3M»'

H:JI:tt «nOJIHMoP'i>mM», a 6eJIKOBhie rrponyKThI, 06pa3yJOIUHec51 B xo.ue 3KCnpeccHH 3T:ttX BapHaHTOB reHa - «nOJIHMoP'i>bI». Pa3Hhie aJIJieJI:tt scTpeqaJOTc51 s rronyJI5IUHH c pa3HOH qacrnrnrt. K noJI11Mopq>aM OTHOC51T TOJihKo re BapttaHThI, pacrrpocT()aHeHHOCTh KOTOphix B nonyJI5IU1I1I He MeHhIIIe l %.

B npouecce 3BOJIJOUHH oTneJihHhie reHhI aMrr -

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K po,IJ,cTBeHHhIM 6eJIKaM OTHOC51T n3o6e.JIKH, npen-

CTaBJIHJOIUHe co6otl: saprraHThl 6eJIKOB, BhlIIOJIH51JOIUHe OLlHY rr TY )Ke cPYHKUHJO rr o6ttap~saeMbie

B rrpe,IJ,eJiax onHoro BH:lla opraHtt3MOB. TaK, s

ne H3 2000 reHOB qeJIOBeKa, KOLJ,HPYJOIUHX ¢aKTOPhI T()aHcKp11rru1111 :11 T()aHcKp:11nu110HHh1e aKTrrsaTOphI, JUJ:eHTHcPHU:HPOBaHO 900, OTHOC511Ul1XC51 K ceMeHCTBY 6eJIKOB, HMelOIUMX «ll,HHKOBble naJihllhl». CYUiecrnyeT 46 reHoB ¢epMeHTa rnnuepanhLl,ern.u- 3-¢oc¢aTllefH:llporeHa3hI, OCYUieCTBJI51JOIUero e,IJ,ttHcrneHHYJO OKHCJIHTeJihHYJO peaKUHIO B MeTa60JIHqecKOM ITYTH Karn6oJitt3Ma rn10K03hI llO n11pysarn.

Bhl51BJieHhI ceMetlcTBa poncTseHHhIX 6eJIKOB,

B03HllKWHe B XO)le 3BOJIJOUHH ll3 O)J,HOfO «IIpe.u-

KOBOfO» retta, HJIH retta-rrpe,IJ,IIIeCTBeHHHKa. Ta- K:tte ceMeHCTBa COCTaBJI51JOT:

loM011orn4ecK1<1e xpoMOCOMbl

P1tc. 4-59. roMonor1t'IHblexpoMOCOMbl It COOTBeTCTBYIOU.\lte annem1M 6enKOBble npc>AyKTbl. Ha p11cyHKe noKa3aHo pacnonolKeH11e 4 annenei'i(AA, Bb, CC, dD) Ha roMonornYHblX xpoMocoMax. Annen11 MOryT 6b1Tb 11A0HTl1YHbl, KaK B cnyo.iae reHOB AA 11 CC, 11n11 paan11o.iaTbC5l (Bb, Dd). 6enKOBb1e npOAYKTbl 6YAYT 11.QeHT11YHbl Afl51 annenei'iAA 11 CC, HO 6YAYT paan11o.iaTbC5l no aM11HoK11cnoTHOi'inocneAOBaTenbHOCTl1 B cnyo.iae annenei'iBb 11 Dd.

•feHbl MHOrJJ06MHa M npoTOMepoB reMorno6MHOB;

•rpyrma rrpoTeOJUITMqecKMX ¢epMeHTOB: TpMnCMH, XHMOTpMITCHH, 3JiaCTa3a, ITJia3MMH, TpOM6MH M HeKOTOpbie Jipyme 6eJIKM M ¢epMeHTbl.

I.I'e.Mouo6u11b1 11e.t106eKa

B xoJie 3BOJifOU:MM M3 eJIMHttqHbIX reHOB-npeJI-

rnecTBeHHMKOB B03HHKJJl.1. CeMeHCTBa reHOB 0,- 11. ~-rno611.HOB (pMc. 4-60), Ha xpoMOCOMax 16 M 11

COOTBeTCTBeHHO.

B npou:ecce omoreHe3a y JIIOJieti o6pa3YfOTCH pa3Hbie B11.JibI reMorno6HHOB, o6ecneqttBaIOUIMe Hall11yqwy10 aJiarrrau:mo K MeH51IOW,MMCH yc110BMHM cyw,ecrnoBaHll51. HbE - 3M6pMOHaJibHbIH, CHHTe3MpyeTc51 y 3apOJibIWa B nepBhie MeC51U:hI pa3BJITH51, HbF - ¢eTaJihHhIH, o6ecrre'fllBaerJiaJlhHetlwee BHYTp11yrpo6Hoe pa3BJITHe ITJIOJia, a HbA M Hb~ ocyw,e- CTBJI51IOT rpaHcrropT Kl1CJIOPOJia B opraHM3Me B3pocJIOro qe110BeKa. 3nt 6e11KH npeJicTaBJI51IOT co6otl TeTpaMepbl, COCT051W,Me 113 nOJIMnem11JIHbIX u:erreti JIByx BMJIOB: a. M ~ B HbA (2o.2~), a, 11 £ B HbE (2a2£), a y OCTaJihHhIX reMOrJI0611HOB ~-u:en11 3aMeHeHbl Ha y-rrommemMJihl B HbF (2a2y) MJIH Ha 8-u:erm B Hb~

(2a28).

IlOJIMMOPcPl13M reMOrJI06MHOB B rrorryJI51U:MM

JIIOJieti oqeHb BeJIMK. Hap51Jiy c reHaMM, KOJI11pyro- W,MMM H306eJIKM M 3aHMMaIOW,MMM pa3Hble JIOKyCbl Ha xpOMOCOMe, o6Hap)')KeHO 6oJibWOe qMCJIO BapttaHTOB reMorno6MHa A, 51BJI51IOW,MXC51 rrpOJIYKTaMM aJIJieJihHhIX reHOB. HeKoTOpbie BapMaHThI HbA rrpeJICTaBJieHbI B Ta6nttu:e 4-9.

CeMeVlcreo a-rnofa1HOBblX

reHOB (xpOMOCOMa 16)

81'1.Qbl reMOrI1061'1HOB

0JIMH M3 HaM6011ee M3BeCTHhlX aJIJieJihHhlX BapMaHTOB HbA - HbS, o6pa3yIOw,Mtic51 B pe3yJibTaTe 3aMeHbl OCTaTKa rnyraMaTa B ITOJIO)KeH11.11.

6 ~-u:err11 HbA Ha BaJIMH (~6 fJiy~BaJI). Ilo aJIJie-

JI5IM HbA M HbS Bcex JifOJieti MO)KHO pa3JieJIMTh Ha

3 reHOTttrrMqecKM pa311Mqa10w,11ec51 rpynnhl: AA,

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