Часть 1 (1120999), страница 79
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During M phase, gene expression shuts do'n'm,and specific modifications are made to histones that help toreorganize the chromatin as it compacts. The compaction is aided by a class ofproteins called condenslns, which use the energy of ATP hydrolysis to help coilthe two DNA molecules in an interphase chromosome to produce the two chromatids of a mitotic chromosome. Condensins are large protein complexes builtfrom SMC protein dimers: these dimers form when two stiff, elongated proteinmonomers join at their tails to form a hinge, leaving two globular head domainsat the other end that bind DNA and hydrolyze ATP (Figure 4-73).\,Vhen addedto purified DNA, condensins can make large right-handed loops in DNAmolecules in a reaction that requires ATP Although it is not yet known how theyact on chromatin, the coiling model shornmin Figure 4-73C is based on the factthat condensins are a major structural component that end up at the core ofmetaphase chromosomes, with about one molecule of condensin for everyFigure4-71 A scanningelectron micrographof a region near one end ofa typical mitotic chromosome.Eachknoblikeprojectionis believedtorepresentthe tip of a separateloopeddomain.Notethat the two identicalpairedchromatids(drawnin Figure4-70) can be clearlydistinguished.(FromM.P.Marsdenand U.K.Laemmli,Cell17:849-858,1979.Withpermissionfrom Elsevier.)chrornatia0 .
1p m244Chapter4: DNA,Chromosomes,and Genomes" b e a d s - o n - a - s t r i"n gform of chromatin30nms e c t i o no fc h r o m o s o m ei nextended formenti remitoticchromosomeITI3 0 - n mc h r o m a t i nfiber of packednucleosomesc o n d e n s e ds e c t i o nof chromosomeTl1 nmTI3 0 0n mretTI700nmiITI1 4 0 0n mN E TR E S U L ET :A C HD N A M O L E C U LHEA SB E E NP A C K A G E IDN T OA M I T O T I CC H R O M O S O MTEH A TI S 1 O , O O O - F OSLHDO R T ETRH A NI T SE X T E N D ELDE N G T HFigure4-73 The SMCproteinsin condensins.(A)Electronmicrographsofa purifiedSMCdimer.(B)Thestructureof a SMCdimer.The long centralregionof this proteinis an antiparallelcoiled-coil(seeFigure3-9) with aflexiblehingein its middle.(C)A modelfor the way in whichthe SMCproteinsin condensinsmight compactchromatin.In reality,SMCproteinsarecomponentsof a much largercondensincomplex.lt hasbeenproposedthat, in the cell,condensinscoil long stringsof loopedchromatindomains(seeFigure4-57).lnthis wa, the condensinscouldform astructuralframeworkthat maintainsthe DNAin a highlyorganizedstateduringmetaphaseof the cellcycle.(A,courtesyof H.P.Erickson;B and C,adaptedfrom T.
Hirano,Not.Rev.Mol.CellBiol.7:311-322,2006.Withpermissionfrom MacmillanPublishersLtd.)Figure4-72 Chromatin packing.Thismodelshowssomeof the manylevelsofchromatinpackingpostulatedto giveriseto the highlycondensedmitoticchromosome.245HOWGENOMESEVOLVEFigure4-74 The locationof condensinin condensedmitotic(A)Fluorescenceatchromosomes.micrographof a humanchromosomemitosis,stainedwith an antibodythat localizesIn chromosomescondensin.inthat arethis highlycondensed,the condensinis seento be concentratedpunctatestructuresshowalongthe chromosomeaxis.Similarexperimentsa similarlocationfor DNAtopoisomerasell,an enzymethat makesreversibledouble-strandbreaksin DNAthat allowone DNAdoublehelixto(A)lHjiJ#l=il:liij$:H';i;i.?;ii],1il"T,",%"J,3"JliX:?n.,".,,0is seenin crosssection,with the chromosometo theaxisperpendicularplaneof the paper.(A,from K.Maeshimaand U.K.Laemmli,Dev.Cell4:467-480,2003.With permissionfrom Elsevier.B,courtesyof U.K.Laemmli,from K.Maeshima,114:365-375,M.
Eltsovand U.K.Laemmli,Chromosoma2005.With permissionfrom Springer,)10,000 nucleotides of DNA (Figure 4-7 4) . \A/hen condensins are experimentallydepleted from a cell, chromosome condensation still occurs, but the process isabnormal.SummaryChromosomesare generallydecondensedduringinterphase, so that the details of theirstructure are dfficult to uisualize.Notable exceptionsare the specializedlampbrushchromosomesof uertebrateoocytesand the polytene chromosomesin the giant secretory cellsof insects.Studiesof thesetwo typesof interphasechromosomessuggestthateach long DNA moleculein a chromosomeis diuided into a large number of discretedomains organizedas loopsof chromatin, each loop probably consistingof a 30-nmchromatinfiber that is compactedbyfurther folding.IAlhengenescontainedin a loopare expressed,the loop unfolds and allows the cell'smachinery accessto the DNA.Interphasechromosomesoccupydiscreteterritories in the cell nucleus;that is,theyare not extensiuelyintertwined.Euchromatin makesup most of interphasechromosomes and, when not being transcribed, it probably existsas tightly folded 30-nmflbers.
Howeuer,euchromatin is interrupted by stretchesof heterochromatin, in whichthe 30-nm fibers are subjectedto additional packing that usually rendersit resistanttogene expression.Heterochromatin existsin seueralforms, some of which arefound inlarge blocks in and around centromeresand near telomeres.But heterochromatin isalso presentat many other positions on chromosomes,where it can serueto regulatedeuelopmentallyimportant genes.The interior of the nucleusk highly dynamic, with heterochromatinoften positioned near the nuclear enuelopeand loops of chromatin mouing away from theirchromosometerritory when genesare ueryhighly expressed.This reflectsthe existenceof nuclearsubcompartments,wheredffirent setsof biochemicalreactionsarefacili'tated by an increasedconcentration of selectedproteins and RNAs.The componentsinuolued in forming a subcompartment can self-assembleinto discreteorganellessuchas nucleoli or Cajal bodies; they can also be tethered to fixed structures such as thenuclearenuelope.During mitosis,geneexpressionshutsdown and all chromosomesadopt a highlycondensedconformation in a processthat beginsearly in M phase to packagethe twoDNA moleculesof each replicated chromosomeas two separatelyfolded chromatids.This processis accompaniedby histone modifications that facilitate chromatin packing.
Howeuer,satisfactorycompletion of this orderly process,which reducesthe end-toend distance of each DNA moleculefrom its interphaselength by an additional factorof ten, requirescondensinproteins.HOWGENOMESEVOLVEIn this chapter, we have discussedthe structure of genes and the ways that theyare packaged and arranged in chromosomes. In this final section, we provide anoverview of some of the ways that genes and genomes have evolved over timeto produce the vast diversity of modern-day life forms on our planet. Genome(B)0 . 5p m246Chapter4: DNA,Chromosomes,and Genomessequencing has revolutionized our view of the process of molecular evolution,uncovering an astonishing wealth of information about specific family relationships among organisms, as well as illuminating evolutionary mechanismsmore generally.It is perhaps not surprising that geneswith similar functions can be found ina diverse range of living things.
But the great revelation of the past 25 years hasbeen the discovery that the actual nucleotide sequencesof many genes are sufficiently well conserved that homologous genes-that is, genes that are similarin both their nucleotide sequence and function because of a common ancestry-can often be recognized across vast phylogenetic distances. For example,unmistakable homologs of many human genesare easyto detect in such organisms as nematode worms, fruit flies, yeasts, and even bacteria. In many cases,the resemblance is so close that the protein-coding portion of a yeast gene canbe substituted with its human homolog-even though we and yeast are separated by more than a billion years of evolutionary history.As emphasized in Chapter 3, the recognition of sequence similarity hasbecome a major tool for inferring gene and protein function.
Although finding asequencematch does not guarantee similarity in function, it has proven to be anexcellentclue.Thus, it is often possibleto predict the function of genesin humansfor which no biochemical or geneticinformation is availablesimply by comparingtheir nucleotide sequenceswith the sequencesof genesin other organisms.In general, gene sequences are more tightly conserved than is overallgenome structure. As we saw earlier, other features of genome organizationsuch as genome size,number of chromosomes,order of genesalong chromosomes, abundance and size of introns, and amount of repetitive DNA are foundto differ greatly among organisms, as does the number of genes that an organism contains.The number of genes is only very roughly correlated with the phenotypiccomplexity of an organism (seeTable l-l).
Much of the increasein gene numberobserved with increasing biological complexity involves the expansion of families of closely related genes, an observation that establishes gene duplicationand divergence as major evolutionary processes.Indeed, it is likely that all present-day genes are descendants-via the processesof duplication, divergence,and reassortment of gene segments-of a few ancestral genes that existed inearly life forms.GenomeAlterationsareCausedby Failuresof the NormalM e c h a n i s mf ors C o p yi n ga n d Ma i n ta i ningDNAcells in the germline do not have specialized mechanisms for creating changesin the structures of their genomes: evolution depends instead on accidents andmistakes followed by nonrandom survival.
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