B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 70
Текст из файла (страница 70)
In the evolution of the Indianmuntjac, initially separate chromosomesfused, without having a major effect on theanimal. These two species contain a similarnumber of genes. (Chinese muntjac photocourtesy of Deborah Carreno, NaturalWonders Photography.)The Nucleotide Sequence of the Human Genome Shows HowOur Genes Are ArrangedFigure 4–15 The organization of genes ona human chromosome. (A) Chromosome22, one of the smallest human chromosomes,contains 48 × 106 nucleotide pairs andmakes up approximately 1.5% of the humangenome.
Most of the left arm of chromosome22 consists of short repeated sequencesof DNA that are packaged in a particularlycompact form of chromatin (heterochromatin)discussed later in this chapter. (B) A tenfoldexpansion of a portion of chromosome 22,with about 40 genes indicated. Those in darkbrown are known genes and those in red arepredicted genes. (C) An expanded portion of(B) showing four genes. (D) The intron–exonarrangement of a typical gene is shownafter a further tenfold expansion. Each exon(red) codes for a portion of the protein, whilethe DNA sequence of the introns (gray) isrelatively unimportant, as discussed in detailin Chapter 6.The human genome (3.2 × 109 nucleotidepairs) is the totality of genetic informationbelonging to our species.
Almost all of thisgenome is distributed over the 22 differentautosomes and 2 sex chromosomes (seeFigures 4–10 and 4–11) found within thenucleus. A minute fraction of the humangenome (16,569 nucleotide pairs—in multiplecopies per cell) is found in the mitochondria(introduced in Chapter 1, and discussedin detail in Chapter 14). The term humangenome sequence refers to the completenucleotide sequence of DNA in the 24nuclear chromosomes and the mitochondria.Being diploid, a human somatic cell nucleuscontains roughly twice the haploid amount ofDNA, or 6.4 × 109 nucleotide pairs, when notduplicating its chromosomes in preparationfor division. (Adapted from InternationalHuman Genome Sequencing Consortium,Nature 409:860–921, 2001.
With permissionfrom Macmillan Publishers Ltd.)MBoC6 m4.14/4.14With the publication of the full DNA sequence of the human genome in 2004, itbecame possible to see in detail how the genes are arranged along each of ourchromosomes (Figure 4–15). It will be many decades before the information contained in the human genome sequence is fully analyzed, but it has already stimulated new experiments that have had major effects on the content of every chapterin this book.(A)human chromosome 22 in its mitotic conformation, composed of twodouble-stranded DNA molecules, each 48 × 106 nucleotide pairs longheterochromatin×1010% of chromosome arm ~40 genes(B)×101% of chromosome arm containing 4 genes(C)×10one gene of 3.4 × 104 nucleotide pairs(D)regulatory DNAsequencesexonintrongene expressionRNAproteinfolded proteinMBoC6 m4.15/4.15184Chapter 4: DNA, Chromosomes, and GenomesTABLE 4–1 Some Vital Statistics for the Human GenomeHuman genomeDNA length3.2 × 109 nucleotide pairs*Number of genes coding for proteinsApproximately 21,000Largest gene coding for protein2.4 × 106 nucleotide pairsMean size for protein-coding genes27,000 nucleotide pairsSmallest number of exons per gene1Largest number of exons per gene178Mean number of exons per gene10.4Largest exon size17,106 nucleotide pairsMean exon size145 nucleotide pairsNumber of noncoding RNA genesApproximately 9000**Number of pseudogenes***More than 20,000Percentage of DNA sequence in exons (protein-codingsequences)1.5%Percentage of DNA in other highly conservedsequences****3.5%Percentage of DNA in high-copy-number repetitiveelementsApproximately 50%* The sequence of 2.85 billion nucleotides is known precisely (error rate of only about 1 in100,000 nucleotides).
The remaining DNA primarily consists of short sequences that aretandemly repeated many times over, with repeat numbers differing from one individual to thenext. These highly repetitive blocks are hard to sequence accurately.** This number is only a very rough estimate.*** A pseudogene is a DNA sequence closely resembling that of a functional gene, butcontaining numerous mutations that prevent its proper expression or function. Mostpseudogenes arise from the duplication of a functional gene followed by the accumulation ofdamaging mutations in one copy.**** These conserved functional regions include DNA encoding 5ʹ and 3ʹ UTRs (untranslatedregions of mRNA), DNA specifying structural and functional RNAs, and DNA with conservedprotein-binding sites.The first striking feature of the human genome is how little of it (only a fewpercent) codes for proteins (Table 4–1 and Figure 4–16).
It is also notable thatnearly half of the chromosomal DNA is made up of mobile pieces of DNA thathave gradually inserted themselves in the chromosomes over evolutionary time,multiplying like parasites in the genome (see Figure 4–62). We discuss these transposable elements in detail in later chapters.A second notable feature of the human genome is the large average genesize—about 27,000 nucleotide pairs. As discussed above, a typical gene carries inits linear sequence of nucleotides the information for the linear sequence of theamino acids of a protein. Only about 1300 nucleotide pairs are required to encodea protein of average size (about 430 amino acids in humans). Most of the remaining sequence in a gene consists of long stretches of noncoding DNA that interruptthe relatively short segments of DNA that code for protein.
As will be discussed indetail in Chapter 6, the coding sequences are called exons; the intervening (noncoding) sequences in genes are called introns (see Figure 4–15 and Table 4–1).The majority of human genes thus consist of a long string of alternating exons andintrons, with most of the gene consisting of introns. In contrast, the majority ofgenes from organisms with concise genomes lack introns. This accounts for themuch smaller size of their genes (about one-twentieth that of human genes), aswell as for the much higher fraction of coding DNA in their chromosomes.(A)(B)Figure 4–16 Scale of the human genome.If drawn with a 1 mm space between eachnucleotide pair, as in (A), the human genomewould extend 3200 km (approximately2000 miles), far enough to stretch acrossthe center ofAfrica,m4.16/4.16the site of our humanMBoC6origins (red line in B).
At this scale, therewould be, on average, a protein-codinggene every 150 m. An average gene wouldextend for 30 m, but the coding sequencesin this gene would add up to only just overa meter.CHROMOSOMAL DNA AND ITS PACKAGING IN THE CHROMATIN FIBERIn addition to introns and exons, each gene is associated with regulatory DNAsequences, which are responsible for ensuring that the gene is turned on or off atthe proper time, expressed at the appropriate level, and only in the proper type ofcell. In humans, the regulatory sequences for a typical gene are spread out overtens of thousands of nucleotide pairs.
As would be expected, these regulatorysequences are much more compressed in organisms with concise genomes. Wediscuss how regulatory DNA sequences work in Chapter 7.Research in the last decade has surprised biologists with the discovery that,in addition to 21,000 protein-coding genes, the human genome contains manythousands of genes that encode RNA molecules that do not produce proteins, butinstead have a variety of other important functions. What is thus far known aboutthese molecules will be presented in Chapters 6 and 7.
Last, but not least, thenucleotide sequence of the human genome has revealed that the archive of information needed to produce a human seems to be in an alarming state of chaos. Asone commentator described our genome, “In some ways it may resemble yourgarage/bedroom/refrigerator/life: highly individualistic, but unkempt; little evidence of organization; much accumulated clutter (referred to by the uninitiatedas ‘junk’); virtually nothing ever discarded; and the few patently valuable itemsindiscriminately, apparently carelessly, scattered throughout.” We shall discusshow this is thought to have come about in the final sections of this chapter entitled“How Genomes Evolve.”Each DNA Molecule That Forms a Linear Chromosome MustContain a Centromere, Two Telomeres, and Replication OriginsTo form a functional chromosome, a DNA molecule must be able to do more thansimply carry genes: it must be able to replicate, and the replicated copies must beseparated and reliably partitioned into daughter cells at each cell division.
Thisprocess occurs through an ordered series of stages, collectively known as the cellcycle, which provides for a temporal separation between the duplication of chromosomes and their segregation into two daughter cells. The cell cycle is brieflysummarized in Figure 4–17, and it is discussed in detail in Chapter 17. Briefly,during a long interphase, genes are expressed and chromosomes are replicated,with the two replicas remaining together as a pair of sister chromatids. Throughout this time, the chromosomes are extended and much of their chromatin existsas long threads in the nucleus so that individual chromosomes cannot be easilydistinguished. It is only during a much briefer period of mitosis that each chromosome condenses so that its two sister chromatids can be separated and distributed to the two daughter nuclei.
The highly condensed chromosomes in adividing cell are known as mitotic chromosomes (Figure 4–18). This is the formin which chromosomes are most easily visualized; in fact, the images of chromosomes shown so far in the chapter are of chromosomes in mitosis.Each chromosome operates as a distinct structural unit: for a copy to be passedon to each daughter cell at division, each chromosome must be able to replicate,and the newly replicated copies must subsequently be separated and partitionedpaternal interphase chromosomenuclear envelopesurrounding the nucleusFigure 4–17 A simplified view of theeukaryotic cell cycle. During interphase,the cell is actively expressing its genesand is therefore synthesizing proteins.Also, during interphase and before celldivision, the DNA is replicated and eachchromosome is duplicated to produce twoclosely paired sister DNA molecules (calledsister chromatids).
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
