Часть 1 (1120999), страница 66
Текст из файла (страница 66)
Amazingly, although the DNA is very tightly folded, it is compacted ina way that keeps it available to the many enz).rnes in the cell that replicate it,repair it, and use its genesto produce RNA molecules and proteins.EucaryoticDNAls Packagedinto a Setof ChromosomesIn eucaryotes,the DNA in the nucleus is divided between a set of different chromosomes. For example, the human genome-approximately 3.2 x 10enucleotides-is distributed over 24 different chromosomes. Each chromosomeconsists of a single, enormously long linear DNA molecule associatedwith proteins that fold and pack the fine DNA thread into a more compact structure.
Thecomplex of DNA and protein is called chromatin (from the Greek chroma,"color," because of its staining properties). In addition to the proteins involvedin packaging the DNA, chromosomes are also associated with many proteinsand RNA molecules required for the processesof gene expression,DNA replication, and DNA repair.Bacteria carry their genes on a single DNA molecule, which is often circular(see Figure 1-29). This DNA is associatedwith proteins that package and condense the DNA, but they are different from the proteins that perform these functions in eucaryotes.Although often called the bacterial "chromosome," it doesnot have the same structure as eucaryotic chromosomes, and less is knoltmabout how the bacterial DNA is packaged.Therefore, our discussion of chromosome structure will focus almost entirely on eucaryotic chromosomes.With the exception of the germ cells (discussed in Chapter 2l) and a fewhighly specialized cell types that cannot multiply and lack DNA altogether (forexample, red blood cells),each human cell contains two copies of each chromosome, one inherited from the mother and one from the father.
The maternal andpaternal chromosomes of a pair are called homologous chromosomes(homologs). The only nonhomologous chromosome pairs are the sex chromosomes in males, where a Y chromosome is inherited from the father and an Xchromosomefrom the mother. Thus, each human cell contains a total of 46 chromosomes-22 pairs common to both males and females, plus two so-called sexchromosomes (X and Y in males, two Xs in females).
DNA hybridization is a technique in which a labeled nucleic acid strand servesas a "probe" that localizes acomplementary strand, as will be described in detail in Chapter B. This technique can be used to distinguish these human chromosomes by "painting" eachone a different color (Figure 4-f0). Chromosome painting is typically done atthe stagein the cell cycle called mitosis, when chromosomes are especiallycompacted and easy to visualize (seebelow).Another more traditional way to distinguish one chromosome from anotherCHROMOSOMALDNAAND ITSPACKAGINGFIBERIN THECHROMATIN(A)(B)-r^along each mitotic chromosome (Figure 4-f l). The structural bases for thesebanding patterns are not well understood.
Nevertheless,the pattern of bands oneach type of chromosome is unique, and it is these patterns that initially allowedeach human chromosome to be identified and numbered.The display of the 46 human chromosomes at mitosis is called the humankaryotype. If parts of chromosomes are lost or are switched between chromosomes, these changes can be detected by changes in the banding patterns or bychanges in the pattern of chromosome painting (Figure 4-12). Cytogeneticistsuse these alterations to detect chromosome abnormalities that are associatedwith inherited defects, as well as to characterize cancers that are associated withspecific chromosome rearrangementsin somatic cells (discussedin Chapter 20).52I5203Figure4-10 The completeset of humanfromchromosomes.Thesechromosomes,a male,wereisolatedfrom a cellandundergoingnucleardivision(mitosis)arethereforehighlycompacted.Eachchromosomehasbeen"painted"adifferentcolorto permitits unambiguousidentificationunderthe light microscope.paintingis performedbyChromosometo a collectionexposingthe chromosomesthat havebeenof humanDNAmoleculescoupledto a combinationof fluorescentderiveddyes.Forexample,DNAmoleculesfrom chromosome1 arelabeledwith onespecificdye combination,those fromchromosome2 with another,and so on.Becausethe labeledDNAcanform basepairs,or hybridize,only to thechromosomefrom which it was derived(discussedin Chapter8),eachchromosomeis differentlylabeled.Forthe chromosomesaresuchexperiments,subjectedto treatmentsthat separatetheDNAinto individualstrands,double-helicalwith thedesignedto permitbase-pairinglabeledDNAwhilesingle-strandedkeepingthe chromosomestructurerelativelyintact.(A)Thechromosomesvisualizedasthey originallyspilledfromthe lysedcell.(B)Thesamechromosomeslinedup in their numericalorder.artificiallyThisarrangementof the full chromosome(FromE.Schrockset is calleda karyotype.Withet al..Science273:494-497,1996.permissionfrom AAAS.)Figure4-1 1 The bandingpatternsofChromosomeshuman chromosomes.order1-22 arenumberedin approximateof size.A typicalhumansomatic(nongerm-line)cellcontainstwo of eachofplustwo sexthesechromosomes,in achromosomes-twoX chromosomesfemale,one X and oneY chromosomein ausedto makemale.The chromosomesthesemapswerestainedat an earlystagearein mitosis,when the chromosomesincompletelycompacted.The horizontolredline representsthe positionof thecentromere(seeFigure4-21),whichappearsas a constrictionon mitoticThe red knobsonchromosomes.c h r o m o s o m e1s3 , ' l 4 ,1 5 , 2 1, a n d 2 2indicatethe positionsof genesthat codeinfor the largeribosomalRNAs(discussedChapter6).Thesepatternsareobtainedbywith Giemsastain,stainingchromosomesand they can be observedunderthe light(Formicrographs,seeFiguremicroscope.21-1 8; adaptedfrom U.
Franke, Cytogenet.1981.WithCellGenet.31:24-32,204Chapter4: DNA,Chromosomes,and Genomesl,?:f J#i,1lff:Tl1flT:ffl[S?ilil:;'1]1,5#: ;i,en,w,hataxia,a diseasecharacterizedby progressivedeteriorationof motor skills.poil, but oneThe patienthasa normalpairof chromosome4s (left-handil?;|;;;:,T:"?;il::::ililiiil:,'""#i.1,ffiff:iil:;:JI:liffi(A)(B)aberrantchromosome12 (redbracket\was deduced,from its patternofbands,asa copyof part of chromosome4 that had becomeattachedto:il:il:::il: l'"*:::l#lit",'*1"f :?il:Tl:T:T;:**il"pairs,"painted"redfor chromosome4 DNA and bluefor chromosome12DNA.Thetwo techniquesgive riseto the sameconclusionregardingthenatureof the aberrantchromosome12,but chromosomeoaintingprovidesbetterresolution,allowingthe clearidentificationof evenshortpiecesof chromosomesthat havebecometranslocated.However,Giemsastainingis easierto perform.(Adaptedfrom E.Schrocket al.,Sclence273:494-497,1996.With permissionf rom AAA5.)ChromosomesContainLongStringsof GenesChromosomes carry genes-the functional units of heredity.
A gene is usuallydefined as a segment of DNA that contains the instructions for making a particular protein (or a set of closely related proteins). Although this definition holdsfor the majority of genes, several percent of genes produce an RNA molecule,instead of a protein, as their final product. Like proteins, these RNA moleculesperform a diverse set of structural and catalltic functions in the cell, and we discuss them in detail in subsequent chapters.As might be expected, some correlation exists between the complexity of anorganism and the number of genes in its genome (see Table l-1, p. 1B). Forexample, some simple bacteria have only 500 genes, compared to about 25,000for humans. Bacteria and some single-celled eucaryotes, such as yeast, haveespecially concise genomes; the complete nucleotide sequence of theirgenomes reveals that the DNA molecules that make up their chromosomes arelittle more than strings of closely packed genes (Figure 4-13).
However, chromosomes from many eucaryotes (including humans) contain, in addition togenes, a large excessof interspersed DNA that does not seem to carry criticalinformation. Sometimes called "junk DNA' to signify that its usefulness to thecell has not been demonstrated, the particular nucleotide sequence of most ofthis DNA may not be important. However, some of this DNA is crucial for theproper expression of certain genes,as we discuss elsewhere.Becauseof differences in the amount of DNA interspersed between genes,genome sizes can vary widely (see Figure l-37). For example, the humangenome is 200 times larger than that of the yeast S.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
