B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 69
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The space inside the endoplasmic reticulum(the ER lumen) is colored yellow; it is continuous with the space between the two nuclear membranes. The lipid bilayers of theinner and outer nuclear membranes are connected at each nuclear pore. A sheetlike network of intermediate filaments (brown)inside the nucleus forms the nuclear lamina (brown), providing mechanical support for the nuclear envelope (for details, seeChapter 12). The dark-staining heterochromatin contains specially condensed regions of DNA that will be discussed later. (A,courtesy of E.G. Jordan and J.
McGovern.)Eukaryotic DNA Is Packaged into a Set of ChromosomesMBoC6 m4.09/4.09Each chromosome in a eukaryotic cell consists of a single, enormously long linearDNA molecule along with the proteins that fold and pack the fine DNA thread intoa more compact structure. In addition to the proteins involved in packaging, chromosomes are also associated with many other proteins (as well as numerous RNAmolecules). These are required for the processes of gene expression, DNA replication, and DNA repair. The complex of DNA and tightly bound protein is calledchromatin (from the Greek chroma, “color,” because of its staining properties).Bacteria lack a special nuclear compartment, and they generally carry theirgenes on a single DNA molecule, which is often circular (see Figure 1–24).
ThisDNA is also associated with proteins that package and condense it, but they aredifferent from the proteins that perform these functions in eukaryotes. Althoughthe bacterial DNA with its attendant proteins is often called the bacterial “chromosome,” it does not have the same structure as eukaryotic chromosomes, andless is known about how the bacterial DNA is packaged. Therefore, our discussionof chromosome structure will focus almost entirely on eukaryotic chromosomes.With the exception of the gametes (eggs and sperm) and a few highly specialized cell types that cannot multiply and either lack DNA altogether (for example,red blood cells) or have replicated their DNA without completing cell division (forexample, megakaryocytes), each human cell nucleus contains two copies of eachchromosome, one inherited from the mother and one from the father.
The maternal and paternal 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 Xchromosome from 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). These human chromosomescan be readily distinguished by “painting” each one a different color using a technique based on DNA hybridization (Figure 4–10). In this method (described indetail in Chapter 8), a short strand of nucleic acid tagged with a fluorescent dyeserves as a “probe” that picks out its complementary DNA sequence, lighting upthe target chromosome at any site where it binds.
Chromosome painting is mostCHROMOSOMAL DNA AND ITS PACKAGING IN THE CHROMATIN FIBER21(A)367891314151920101621451112171822X X(B)10 µmfrequently done at the stage in the cell cycle called mitosis, when chromosomesare especially compacted and easy to visualize (see below).Another more traditional way to distinguish one chromosome from anotheris to stain them with dyes that reveal a striking and reproducible pattern of bandsalong each mitotic chromosome (Figure 4–11). These banding patterns presumably reflect variations in chromatin structure, but their basis is not well understood. Nevertheless, the pattern of bands on each type of chromosome is unique,MBoC6 ton4.444/4.10and it provided the initial meansidentify and number each human chromosome reliably.374589101112612191613141517Y21201850 millionnucleotide pairs221 µmX181Figure 4–10 The complete set of humanchromosomes.
These chromosomes,from a female, were isolated from a cellundergoing nuclear division (mitosis)and are therefore highly compacted.Each chromosome has been “painted” adifferent color to permit its unambiguousidentification under the fluorescencemicroscope, using a technique called“spectral karyotyping.” Chromosomepainting can be performed by exposingthe chromosomes to a large collection ofDNA molecules whose sequence matchesknown DNA sequences from the humangenome. The set of sequences matchingeach chromosome is coupled to a differentcombination of fluorescent dyes.
DNAmolecules derived from chromosome 1 arelabeled with one specific dye combination,those from chromosome 2 with another,and so on. Because the labeled DNA canform base pairs, or hybridize, only to thechromosome from which it was derived,each chromosome becomes labeledwith a different combination of dyes. Forsuch experiments, the chromosomes aresubjected to treatments that separatethe two strands of double-helical DNA ina way that permits base-pairing with thesingle-stranded labeled DNA, but keepsthe overall chromosome structure relativelyintact.
(A) The chromosomes visualized asthey originally spilled from the lysed cell.(B) The same chromosomes artificiallylined up in their numerical order. Thisarrangement of the full chromosomeset is called a karyotype. (Adapted fromN. McNeil and T.
Ried, Expert Rev. Mol.Med. 2:1–14, 2000. With permission fromCambridge University Press.)Figure 4–11 The banding patterns ofhuman chromosomes. Chromosomes1–22 are numbered in approximate orderof size. A typical human cell contains twoof each of these chromosomes, plus twosex chromosomes—two X chromosomesin a female, one X and one Y chromosomein a male. The chromosomes used tomake these maps were stained at an earlystage in mitosis, when the chromosomesare incompletely compacted. Thehorizontal red line represents the positionof the centromere (see Figure 4–19),which appears as a constriction onmitotic chromosomes. The red knobs onchromosomes 13, 14, 15, 21, and 22indicate the positions of genes that codefor the large ribosomal RNAs (discussedin Chapter 6). These banding patterns areobtained by staining chromosomes withGiemsa stain, and they can be observedunder the light microscope.
(Adapted fromU. Francke, Cytogenet. Cell Genet. 31:24–32, 1981. With permission from the author.)182Chapter 4: DNA, Chromosomes, and GenomesFigure 4–12 Aberrant human chromosomes. (A) Two normal humanchromosomes, 4 and 6. (B) In an individual carrying a balanced chromosomaltranslocation, the DNA double helix in one chromosome has crossed overwith the DNA double helix in the other chromosome due to an abnormalrecombination event. The chromosome painting technique used on thechromosomes in each of the sets allows the identification of even shortpieces of chromosomes that have become translocated, a frequent event incancer cells.
(Courtesy of Zhenya Tang and the NIGMS Human Genetic CellRepository at the Coriell Institute for Medical Research: GM21880.)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 either by changes in the banding patternsor—with greater sensitivity—by changes in the pattern of chromosome painting(Figure 4–12).
Cytogeneticists use these alterations to detect inherited chromosome abnormalities and to reveal the chromosome rearrangements that occur incancer cells as they progress to malignancy (discussed in Chapter 20).(A)chromosome 6chromosome 4Chromosomes Contain Long Strings of GenesChromosomes carry genes—the functional units of heredity. A gene is oftendefined as a segment of DNA that contains the instructions for making a particular protein (or a set of closely related proteins), but this definition is too narrow.Genes that code for protein are indeed the majority, and most of the genes withclear-cut mutant phenotypes fall under this heading.
In addition, however, thereare many “RNA genes”—segments of DNA that generate a functionally significantRNA molecule, instead of a protein, as their final product. We shall say more aboutthe RNA genes and their products later.As might be expected, some correlation exists between the complexity ofan organism and the number of genes in its genome (see Table 1–2, p. 29). Forexample, some simple bacteria have only 500 genes, compared to about 30,000for humans. Bacteria, archaea, and some single-celled eukaryotes, such as yeast,have concise genomes, consisting of little more than strings of closely packedgenes. However, the genomes of multicellular plants and animals, as well as manyother eukaryotes, contain, in addition to genes, a large quantity of interspersedDNA whose function is poorly understood (Figure 4–13).
Some of this additionalDNA is crucial for the proper control of gene expression, and this may in partexplain why there is so much of it in multicellular organisms, whose genes have tobe switched on and off according to complicated rules during development (discussed in Chapters 7 and 21).Differences in the amount of DNA interspersed between genes, far more thandifferences in numbers of genes, account for the astonishing variations in genomesize that we see when we compare one species with another (see Figure 1–32). Forexample, the human genome is 200 times larger than that of the yeast Saccharomyces cerevisiae, but 30 times smaller than that of some plants and amphibiansand 200 times smaller than that of a species of amoeba.
Moreover, because of differences in the amount of noncoding DNA, the genomes of closely related organisms (bony fish, for example) can vary several hundredfold in their DNA content,even though they contain roughly the same number of genes. Whatever the excess(A) Saccharomyces cerevisiae0102030 kilobases102030 kilobases(B) human0genegenome-wide repeat(B)reciprocal chromosomal translocationMBoC6 n4.546/4.12Figure 4–13 The arrangement ofgenes in the genome of S. cerevisiaecompared to humans.
(A) S. cerevisiae isa budding yeast widely used for brewingand baking. The genome of this singlecelled eukaryote is distributed over 16chromosomes. A small region of onechromosome has been arbitrarily selectedto show its high density of genes. (B) Aregion of the human genome of equallength to the yeast segment in (A). Thehuman genes are much less denselypacked and the amount of interspersedDNA sequence is far greater. Not shown inthis sample of human DNA is the fact thatmost human genes are much longer thanyeast genes (see Figure 4–15).CHROMOSOMAL DNA AND ITS PACKAGING IN THE CHROMATIN FIBER183Y2 X Y1X YChinese muntjacIndian muntjacDNA may do, it seems clear that it is not a great handicap for a eukaryotic cell tocarry a large amount of it.How the genome is divided into chromosomes also differs from one eukaryoticspecies to the next.
For example, while the cells of humans have 46 chromosomes,those of some small deer have only 6, while those of the common carp containover 100. Even closely related species with similar genome sizes can have verydifferent numbers and sizes of chromosomes (Figure 4–14). Thus, there is no simple relationship between chromosome number, complexity of the organism, andtotal genome size. Rather, the genomes and chromosomes of modern-day specieshave each been shaped by a unique history of seemingly random genetic events,acted on by poorly understood selection pressures over long evolutionary times.Figure 4–14 Two closely related speciesof deer with very different chromosomenumbers.
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