9 Геном, плазмиды, вирусы (Лекции), страница 2

Each chromosome ofa eukaryotic cell, such as that shown in Figure 23-4a, can contain asingle, very large, duplex DNA molecule, which may be from 4 to 100times larger than that of anE. coli cell. For example, the DNA of one ofthe smaller human chromosomes has a contour length of about 30 mm,almost 15 times longer than the DNA of E. coli. The DNA molecules inthe 24 different types of chromosomes of human cells (22 + X + Y)vary in length over a 25-fold range. Each different chromosome in eukaryotes carries a characteristic set of genes.Chapter 23 Genes and Chromosomes795Figure 23-4 Eukaryotic chromosomes, (a) A chromosome from a human cell, (b) A complete set ofchromosomes from a leukocyte from one of the authors. There are 46 chromosomes in every humansomatic cell.Organelles of Eukaryotic Cells Also Contain DNAIn addition to the DNA in the nucleus of eukaryotic cells, very smallamounts of DNA, differing in base sequence from nuclear DNA, arepresent within the mitochondria.

Chloroplasts of photosynthetic cellsalso contain DNA. Usually less than 0.1% of all the cell DNA is presentin the mitochondria in typical somatic cells, but in fertilized and dividing egg cells, where the mitochondria are much more numerous, thetotal amount of mitochondrial DNA is correspondingly larger. Mitochondrial DNA (mDNA) is a very small molecule compared with thenuclear chromosomes. In animal cells it contains less than 20,000 basepairs (16,569 base pairs in human mDNA) and occurs as a circularduplex.

Chloroplast DNA molecules also exist as circular duplexes andare considerably larger than those of mitochondria.The evolutionary origin of mitochondrial and chloroplast DNAshas been the subject of much speculation. A widely accepted view isthat they are vestiges of the chromosomes of ancient bacteria thatgained access to the cytoplasm of host cells and became the precursorsof these organelles (see Fig. 2-17). Mitochondrial DNA codes for themitochondrial tRNAs and rRNAs and for a few mitochondrial proteins.More than 95% of mitochondrial proteins are encoded by nuclear DNA.Mitochondria and chloroplasts divide when the cell divides (Fig. 23-5).Before and during division of these organelles their DNA is replicatedand the daughter DNA molecules pass into the daughter organelles.^(a)**(b)Figure 23-5 A dividing mitochondrion.

Many mitochondrial proteins and RNAs are encoded by themitochondrial DNA (not visible here), which is replicated each time the mitochondrion divides.Part IV Information Pathways796Genes Are Segments of DNA That Code for PolypeptideChains and RNAsDNAmRNAPolypeptide5' | | 3'CinGGniCTinAGniCGniCAinTTinAAn iT| 5'C "1G \it AminoI terminusArgUjG }•GlyAJu]A \CJTyrC [ThrTMIATMIATMIAU [PheGmCCinGCinGGmCC yCIMGAM ITCinGTinATMIATinATinACinGujGlcJU [TMIA3' |Ala| 5'ValSerCarboxylterminusTemplate strandFigure 23-6 Colinearity of the nucleotide sequences of DNA, mRNA, and the amino acid sequence of polypeptide chains.

The triplets of nucleotide units in DNA determine the sequence of aminoacids in proteins through the intermediary formation of mRNA, which has nucleotide triplets (codons) complementary to those of the DNA. Onlyone of the DNA strands, the template strand,serves as a template for mRNA synthesis.Our present understanding of the gene has evolved considerably overthe last century.

A gene is defined in the classical biological sense as aportion of a chromosome that determines or affects a single characteror phenotype (visible property), for example, eye color. But there isalso a molecular definition, first proposed by George Beadle and Edward Tatum in 1940. They exposed spores of the mold Neurosporacrassa to x rays and other agents that damage DNA and sometimescause alterations in the DNA sequence (mutations). Some mutantswere found to be deficient in one or another specific enzyme, resultingin the failure of a metabolic pathway.

This observation led Beadle andTatum to conclude that a gene is a segment of the genetic material thatdetermines or codes for one enzyme: the one gene-one enzyme hypothesis. Later this concept was broadened to one gene-one protein,because many genes code for proteins that are not enzymes.The present biochemical definition of a gene is somewhat moreprecise. Recall that many proteins have multiple polypeptide chains(Chapter 6).

In some multichain proteins, all the polypeptide chainsare identical, in which case they can all be encoded by the same gene.Others have two or more different kinds of polypeptide chains, eachwith a distinctive amino acid sequence. Hemoglobin A, the major adulthemoglobin of humans, for example, has two kinds of polypeptidechains, a and /3 chains, which differ in amino acid sequence and areencoded by two different genes. Thus the gene—protein relationship ismore accurately described by the phrase "one gene-one polypeptide."However, not all genes are ultimately expressed in the form ofpolypeptide chains.

Some genes code for the different kinds of RNAssuch as tRNAs and rRNAs (Chapters 12 and 25). Genes that code foreither polypeptides or RNAs are known as structural genes: theyencode the primary sequence of some final gene product, such as anenzyme or a stable RNA. DNA also contains other segments or sequences that have a purely regulatory function. Regulatory sequences provide signals that may denote the beginning and end ofstructural genes, or participate in turning on or off the transcription ofstructural genes, or function as initiation points for replication or recombination (Chapter 27).The minimum overall size of genes can be estimated directly.

Aswill be described in detail in Chapter 26, each amino acid of a polypeptide chain is coded by a sequence of three consecutive nucleotides in asingle strand of DNA (Fig. 23-6). Because there are no signals for"commas" in the genetic code, the coding triplets of DNA are generallyarranged sequentially, corresponding to the sequence of amino acids inthe polypeptide for which it codes. Figure 23-6 shows the principle ofthe coding relationships between DNA, RNA, and proteins. A singlepolypeptide chain may have anywhere from about fifty to several thousand amino acid residues in a specific sequence, thus a gene coding forthe biosynthesis of a polypeptide chain must have, correspondingly, atleast 150 to 6,000 or more base pairs.

For an average polypeptide chainof 350 amino acid residues, this would correspond to 1,050 base pairs.We will see later that many genes in eukaryotes and a few in prokaryotes are interrupted by noncoding DNA segments called introns, andcan therefore be considerably longer than the simple calculations outlined above would suggest.Chapter 23 Genes and Chromosomes797There Are Many Genes in a Single ChromosomeHow many genes are in a single chromosome? We can give an approximate answer to this question in the case of E. coli. If the average geneis 1,050 base pairs long, the 4.7 million base pairs in the E. coli chromosome could accommodate about 4,400 genes.

The products of over 1,000E. coli genes have already been characterized, and the number is increasing. A growing fraction of the E. coli chromosome has been sequenced, and the number of genes it contains will be known with someprecision when this effort is completed.Eukaryotic Chromosomes Are Very ComplexBacteria usually have only one chromosome per cell, and in nearly allcases each chromosome contains only one copy of any given gene. Avery few genes, such as those for rRNAs, are repeated several times.Regulatory and structural gene sequences account for much of theDNA in prokaryotes.

Moreover, almost every gene is precisely colinearwith the amino acid sequence (or RNA sequence) for which it codes(Fig. 23-6).The organization of genes in eukaryotic DNA is structurally andfunctionally much more complex, and the study of eukaryotic chromosome structure has yielded many surprises.

Tests made of the extent towhich segments of mouse DNA occur in multiple copies had an unexpected outcome. About 10% of mouse DNA consists of short lengths ofless than 10 base pairs that are repeated millions of times per cell.These are called highly repetitive segments. Another 20% of mouseDNA was found to occur in lengths up to a few hundred base pairs thatare repeated at least 1,000 times, designated moderately repetitive.The remainder, some 70% of the DNA, consists of unique segments andsegments that are repeated only a few times.Some of the repetitive DNA may simply be "junk DNA," vestiges ofevolutionary sidetracks.

At least some of it has functional significance,however. The most highly repeated sequences are called satelliteDNA because their base compositions are generally unusual, permitting their separation from the rest of the DNA when fragmented cellular DNA samples are centrifuged in cesium chloride density gradients.Satellite DNA is not believed to encode proteins or RNAs.