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Prokaryotic eukaryoticgenome

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    Prokaryotic eukaryoticgenome Prokaryotic eukaryoticgenome Presentation Transcript

    • The Genetics of Viruses and Bacteria
      • Viruses called bacteriophages
        • Can infect and set in motion a genetic takeover of bacteria, such as Escherichia coli
      Figure 18.1 0.5 m
      • Recall that bacteria are prokaryotes
        • With cells much smaller and more simply organized than those of eukaryotes
      • Viruses
        • Are smaller and simpler still
      Figure 18.2 0.25 m Virus Animal cell Bacterium Animal cell nucleus
      • A virus has a genome but can reproduce only within a host cell
      • Scientists were able to detect viruses indirectly
        • Long before they were actually able to see them
      For example: Tobacco mosaic disease stunts the growth of tobacco plants and gives their leaves a mosaic coloration Figure 18.3
      • In the late 1800s
        • Researchers hypothesized that a particle smaller than bacteria caused tobacco mosaic disease
      • In 1935, Wendell Stanley
        • Confirmed this hypothesis when he crystallized the infectious particle, now known as tobacco mosaic virus (TMV)
    • Structure of Viruses
      • Viruses
        • Are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope
      • Viral genomes may consist of
        • Double- or single-stranded DNA
        • Double- or single-stranded RNA
    • Capsids and Envelopes
      • A capsid
        • Is the protein shell that encloses the viral genome
        • Can have various structures
      Figure 18.4a, b 18  250 mm 70–90 nm (diameter) 20 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses RNA DNA Capsomere Glycoprotein Capsomere of capsid
      • Some viruses have envelopes
        • Which are membranous coverings derived from the membrane of the host cell
      Figure 18.4c 80–200 nm (diameter) 50 nm (c) Influenza viruses RNA Glycoprotein Membranous envelope Capsid
      • Bacteriophages, also called phages
        • Have the most complex capsids found among viruses
      Figure 18.4d 80  225 nm 50 nm (d) Bacteriophage T4 DNA Head Tail fiber Tail sheath
    • General Features of Viral Reproductive Cycles
      • Viruses are obligate intracellular parasites
        • They can reproduce only within a host cell
      • Each virus has a host range
        • A limited number of host cells that it can infect
      • Viruses use enzymes, ribosomes, and small molecules of host cells
        • To synthesize progeny viruses
      VIRUS Capsid proteins mRNA Viral DNA HOST CELL Viral DNA DNA Capsid Figure 18.5 Entry into cell and uncoating of DNA Replication Transcription Self-assembly of new virus particles and their exit from cell
    • Reproductive Cycles of Phages
      • Phages
        • Are the best understood of all viruses
        • Go through two alternative reproductive mechanisms: the lytic cycle and the lysogenic cycle
    • The Lytic Cycle
      • The lytic cycle
        • Is a phage reproductive cycle that culminates in the death of the host
        • Produces new phages and digests the host’s cell wall, releasing the progeny viruses
      • The lytic cycle of phage T4, a virulent phage
      Phage assembly Head Tails Tail fibers Figure 18.6 Attachment. The T4 phage uses its tail fibers to bind to specific receptor sites on the outer surface of an E. coli cell. 1 Entry of phage DNA and degradation of host DNA. The sheath of the tail contracts, injecting the phage DNA into the cell and leaving an empty capsid outside. The cell’s DNA is hydrolyzed. 2 Synthesis of viral genomes and proteins. The phage DNA directs production of phage proteins and copies of the phage genome by host enzymes, using components within the cell. 3 Assembly. Three separate sets of proteins self-assemble to form phage heads, tails, and tail fibers. The phage genome is packaged inside the capsid as the head forms. 4 Release. The phage directs production of an enzyme that damages the bacterial cell wall, allowing fluid to enter. The cell swells and finally bursts, releasing 100 to 200 phage particles. 5
    • The Lysogenic Cycle
      • The lysogenic cycle
        • Replicates the phage genome without destroying the host
      • Temperate phages
        • Are capable of using both the lytic and lysogenic cycles of reproduction
      • The lytic and lysogenic cycles of phage  , a temperate phage
      Many cell divisions produce a large population of bacteria infected with the prophage. The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. Phage DNA integrates into the bacterial chromosome, becoming a prophage. New phage DNA and proteins are synthesized and assembled into phages. Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Certain factors determine whether The phage attaches to a host cell and injects its DNA. Phage DNA circularizes The cell lyses, releasing phages. Lytic cycle is induced Lysogenic cycle is entered Lysogenic cycle Lytic cycle or Prophage Bacterial chromosome Phage Phage DNA Figure 18.7
    • Viral Envelopes
      • Many animal viruses
        • Have a membranous envelope
      • The broadest variety of RNA genomes
        • Is found among the viruses that infect animals
      • Viral glycoproteins on the envelope
        • Bind to specific receptor molecules on the surface of a host cell
      Table 18.1
      • The reproductive cycle of an enveloped RNA virus
      RNA Capsid Envelope (with glycoproteins) HOST CELL Viral genome (RNA) Template Capsid proteins Glyco- proteins mRNA Copy of genome (RNA) ER Figure 18.8 Glycoproteins on the viral envelope bind to specific receptor molecules (not shown) on the host cell, promoting viral entry into the cell. 1 Capsid and viral genome enter cell 2 The viral genome (red) functions as a template for synthesis of complementary RNA strands (pink) by a viral enzyme. 3 New copies of viral genome RNA are made using complementary RNA strands as templates. 4 Complementary RNA strands also function as mRNA, which is translated into both capsid proteins (in the cytosol) and glycoproteins for the viral envelope (in the ER). 5 Vesicles transport envelope glycoproteins to the plasma membrane. 6 A capsid assembles around each viral genome molecule. 7 New virus 8
      • Retroviruses, such as HIV, use the enzyme reverse transcriptase
        • To copy their RNA genome into DNA, which can then be integrated into the host genome as a provirus
      Figure 18.9 Reverse transcriptase Viral envelope Capsid Glycoprotein RNA (two identical strands)
      • The reproductive cycle of HIV, a retrovirus
      Figure 18.10 mRNA RNA genome for the next viral generation Viral RNA RNA-DNA hybrid DNA Chromosomal DNA NUCLEUS Provirus HOST CELL Reverse transcriptase New HIV leaving a cell HIV entering a cell 0.25 µm HIV Membrane of white blood cell The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. 1 Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. 2 Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. 3 The double-stranded DNA is incorporated as a provirus into the cell’s DNA. 4 Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. 5 The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). 6 Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. 7 Capsids are assembled around viral genomes and reverse transcriptase molecules. 8 New viruses bud off from the host cell. 9
    • Evolution of Viruses
      • Viruses do not really fit our definition of living organisms (no cellular structure)
      • Viruses, viroids, and prions are formidable pathogens in animals and plants
      • Diseases caused by viral infections
        • Affect humans, agricultural crops, and livestock worldwide
    • Viral Diseases in Animals
      • Viruses may damage or kill cells
        • By causing the release of hydrolytic enzymes from lysosomes
      • Some viruses cause infected cells
        • To produce toxins that lead to disease symptoms
      • Vaccines
        • Are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen
        • Can prevent certain viral illnesses
      • Emerging viruses
        • Are those that appear suddenly or suddenly come to the attention of medical scientists
      • Severe acute respiratory syndrome (SARS)
        • Recently appeared in China
      • Outbreaks of “new” viral diseases in humans
        • Are usually caused by existing viruses that expand their host territory
      (a) Young ballet students in Hong Kong wear face masks to protect themselves from the virus causing SARS. (b) The SARS-causing agent is a coronavirus like this one (colorized TEM), so named for the “corona” of glycoprotein spikes protruding from the envelope.
    • Viral Diseases in Plants
      • More than 2,000 types of viral diseases of plants are known
      • Common symptoms of viral infection include
        • Spots on leaves and fruits, stunted growth, and damaged flowers or roots
      Figure 18.12
      • Plant viruses spread disease in two major modes
        • Horizontal transmission, entering through damaged cell walls
        • Vertical transmission, inheriting the virus from a parent
    • Viroids and Prions: The Simplest Infectious Agents
      • Viroids
        • Are circular RNA molecules that infect plants and disrupt their growth
      • Prions
        • Are slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals
        • Propagate by converting normal proteins into the prion version
      Figure 18.13 Prion Normal protein Original prion New prion Many prions
      • Rapid reproduction, mutation, and genetic recombination contribute to the genetic diversity of bacteria
      • Bacteria allow researchers
        • To investigate molecular genetics in the simplest true organisms
    • The Bacterial Genome and Its Replication
      • The bacterial chromosome
        • Is usually a circular DNA molecule with few associated proteins
      • In addition to the chromosome
        • Many bacteria have plasmids, smaller circular DNA molecules that can replicate independently of the bacterial chromosome
      • Bacterial cells divide by binary fission
        • Which is preceded by replication of the bacterial chromosome
      Replication fork Origin of replication Termination of replication Figure 18.14
    • Mutation and Genetic Recombination as Sources of Genetic Variation
      • Since bacteria can reproduce rapidly
        • New mutations can quickly increase a population’s genetic diversity
    • Mechanisms of Gene Transfer and Genetic Recombination in Bacteria
      • Three processes bring bacterial DNA from different individuals together
        • Transformation
        • Transduction
        • Conjugation
    • Transformation
      • Transformation
        • Is the alteration of a bacterial cell’s genotype and phenotype by the uptake of naked, foreign DNA from the surrounding environment
    • Transduction
      • In the process known as transduction
        • Phages carry bacterial genes from one host cell to another
      1 Figure 18.16 Donor cell Recipient cell A + B + A + A + B – A – B – A + Recombinant cell Crossing over Phage infects bacterial cell that has alleles A + and B + Host DNA (brown) is fragmented, and phage DNA and proteins are made. This is the donor cell. A bacterial DNA fragment (in this case a fragment with the A + allele) may be packaged in a phage capsid. Phage with the A + allele from the donor cell infects a recipient A – B – cell, and crossing over (recombination) between donor DNA (brown) and recipient DNA (green) occurs at two places (dotted lines). The genotype of the resulting recombinant cell ( A + B – ) differs from the genotypes of both the donor ( A + B + ) and the recipient ( A – B – ). 2 3 4 5 Phage DNA A + B +
    • Conjugation and Plasmids
      • Conjugation
        • Is the direct transfer of genetic material between bacterial cells that are temporarily joined
      Figure 18.17 Sex pilus 1 m
    • The F Plasmid and Conjugation
      • Cells containing the F plasmid, designated F + cells
        • Function as DNA donors during conjugation
        • Transfer plasmid DNA to an F  recipient cell
      Figure 18.18a A cell carrying an F plasmid (an F + cell) can form a mating bridge with an F – cell and transfer its F plasmid. A single strand of the F plasmid breaks at a specific point (tip of blue arrowhead) and begins to move into the recipient cell. As transfer continues, the donor plasmid rotates (red arrow). 2 DNA replication occurs in both donor and recipient cells, using the single parental strands of the F plasmid as templates to synthesize complementary strands. 3 The plasmid in the recipient cell circularizes. Transfer and replication result in a compete F plasmid in each cell. Thus, both cells are now F + . 4 F Plasmid Bacterial chromosome Bacterial chromosome F + cell F + cell F + cell Mating bridge 1 Conjugation and transfer of an F plasmid from an F + donor to an F – recipient (a) F – cell
      • Chromosomal genes can be transferred during conjugation
        • When the donor cell’s F factor is integrated into the chromosome
      • A cell with the F factor built into its chromosome
        • Is called an Hfr cell
      • The F factor of an Hfr cell
        • Brings some chromosomal DNA along with it when it is transferred to an F – cell
      • Conjugation and transfer of part of the bacterial chromosome from an Hfr donor to an F – recipient, resulting in recombination
      Figure 18.18b F + cell Hfr cell F factor The circular F plasmid in an F + cell can be integrated into the circular chromosome by a single crossover event (dotted line). 1 The resulting cell is called an Hfr cell (for High frequency of recombination). 2 Since an Hfr cell has all the F-factor genes, it can form a mating bridge with an F – cell and transfer DNA. 3 A single strand of the F factor breaks and begins to move through the bridge. DNA replication occurs in both donor and recipient cells, resulting in double-stranded DNA 4 The location and orientation of the F factor in the donor chromosome determine the sequence of gene transfer during conjugation. In this example, the transfer sequence for four genes is A-B-C-D. 5 The mating bridge usually breaks well before the entire chromosome and the rest of the F factor are transferred. 6 Two crossovers can result in the exchange of similar (homologous) genes between the transferred chromosome fragment (brown) and the recipient cell’s chromosome (green). 7 The piece of DNA ending up outside the bacterial chromosome will eventually be degraded by the cell’s enzymes. The recipient cell now contains a new combination of genes but no F factor; it is a recombinant F – cell. 8 Temporary partial diploid Recombinant F – bacterium A + B + C + D + F – cell A – B – C – D – A – B – C – D – D – A – C – B – A + B + C + D + A + B + D + C + A + A + B + A – B – C – D – A – B + C – D – A + B + B – A + Hfr cell D – A – C – B – A + B + C + D + A + B + Conjugation and transfer of part of the bacterial chromosome from an Hfr donor to an F – recipient, resulting in recombination (b)
    • R plasmids and Antibiotic Resistance
      • R plasmids
        • Confer resistance to various antibiotics
      • Transposable elements
        • Can move around within a cell’s genome
        • Are often called “jumping genes”
        • Contribute to genetic shuffling in bacteria
    • Insertion Sequences
      • An insertion sequence contains a single gene for transposase
        • An enzyme that catalyzes movement of the insertion sequence from one site to another within the genome
      Figure 18.19a (a) Insertion sequences, the simplest transposable elements in bacteria, contain a single gene that encodes transposase, which catalyzes movement within the genome. The inverted repeats are backward, upside-down versions of each other; only a portion is shown. The inverted repeat sequence varies from one type of insertion sequence to another. Insertion sequence Transposase gene Inverted repeat Inverted repeat 3 5 3 5 A T C C G G T… T A G G C C A … A C C G G A T… T G G C C T A …
    • Transposons
      • Bacterial transposons
        • Also move about within the bacterial genome
        • Have additional genes, such as those for antibiotic resistance
      Figure 18.19b (b) Transposons contain one or more genes in addition to the transposase gene. In the transposon shown here, a gene for resistance to an antibiotic is located between twin insertion sequences. The gene for antibiotic resistance is carried along as part of the transposon when the transposon is inserted at a new site in the genome. Inverted repeats Transposase gene Insertion sequence Insertion sequence Antibiotic resistance gene Transposon 5 3 5 3
      • Individual bacteria respond to environmental change by regulating their gene expression
      • E. coli , a type of bacteria that lives in the human colon
        • Can tune its metabolism to the changing environment and food sources
      • This metabolic control occurs on two levels
        • Adjusting the activity of metabolic enzymes already present
        • Regulating the genes encoding the metabolic enzymes
      Figure 18.20a, b (a) Regulation of enzyme activity Enzyme 1 Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 Regulation of gene expression Feedback inhibition Tryptophan Precursor (b) Regulation of enzyme production Gene 2 Gene 1 Gene 3 Gene 4 Gene 5 – –
    • Operons: The Basic Concept
      • In bacteria, genes are often clustered into operons, composed of
        • An operator, an “on-off” switch
        • A promoter
        • Genes for metabolic enzymes
      • An operon
        • Is usually turned “on”
        • Can be switched off by a protein called a repressor
    • Video Clip – trp operon
      • The trp operon: regulated synthesis of repressible enzymes
      Figure 18.21a (a) Tryptophan absent, repressor inactive, operon on. RNA polymerase attaches to the DNA at the promoter and transcribes the operon’s genes. Genes of operon Inactive repressor Protein Operator Polypeptides that make up enzymes for tryptophan synthesis Promoter Regulatory gene RNA polymerase Start codon Stop codon Promoter trp operon 5 3 mRNA 5 trpD trpE trpC trpB trpA trpR DNA mRNA E D C B A
    • DNA mRNA Protein Tryptophan (corepressor) Active repressor No RNA made Tryptophan present, repressor active, operon off. As tryptophan accumulates, it inhibits its own production by activating the repressor protein. (b) Figure 18.21b
    • Repressible and Inducible Operons: Two Types of Negative Gene Regulation
      • In a repressible operon
        • Binding of a specific repressor protein to the operator shuts off transcription
      • In an inducible operon
        • Binding of an inducer to an innately inactive repressor inactivates the repressor and turns on transcription
    • Video Clip – Lac Operon
      • The lac operon: regulated synthesis of inducible enzymes
      Figure 18.22a DNA mRNA Protein Active repressor RNA polymerase No RNA made lacZ lacl Regulatory gene Operator Promoter Lactose absent, repressor active, operon off. The lac repressor is innately active, and in the absence of lactose it switches off the operon by binding to the operator. (a) 5 3
    • mRNA 5' DNA mRNA Protein Allolactose (inducer) Inactive repressor lacl lacz lacY lacA RNA polymerase Permease Transacetylase  -Galactosidase 5 3 (b) Lactose present, repressor inactive, operon on. Allolactose, an isomer of lactose, derepresses the operon by inactivating the repressor. In this way, the enzymes for lactose utilization are induced. mRNA 5 lac operon Figure 18.22b
      • Inducible enzymes
        • Usually function in catabolic pathways (break down)
      • Repressible enzymes
        • Usually function in anabolic pathways (build up)
      • Regulation of both the trp and lac operons
        • Involves the negative control of genes, because the operons are switched off by the active form of the repressor protein
      Figure 18.22a DNA mRNA Protein Active repressor RNA polymerase No RNA made lacZ lacl Regulatory gene Operator Promoter Lactose absent, repressor active, operon off. (a) 5 3 DNA mRNA Protein Tryptophan (corepressor) Active repressor No RNA made Tryptophan present, repressor active, operon off (b) Figure 18.21b
    • Positive Gene Regulation
      • Some operons are also subject to positive control
        • Via a stimulatory activator protein, such as catabolite activator protein (CAP)
      • In E. coli , when glucose, a preferred food source, is scarce
        • The lac operon is activated by the binding of a regulatory protein, catabolite activator protein (CAP)
      Promoter Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized. If glucose is scarce, the high level of cAMP activates CAP, and the lac operon produces large amounts of mRNA for the lactose pathway. (a) CAP-binding site Operator RNA polymerase can bind and transcribe Inactive CAP Active CAP cAMP DNA Inactive lac repressor lacl lacZ Figure 18.23a
    • Video Clip
      • When glucose levels in an E. coli cell increase
        • CAP detaches from the lac operon, turning it off
      Figure 18.23b (b) Lactose present, glucose present (cAMP level low): little lac mRNA synthesized. When glucose is present, cAMP is scarce, and CAP is unable to stimulate transcription. Inactive lac repressor Inactive CAP DNA RNA polymerase can’t bind Operator lacl lacZ CAP-binding site Promoter
    • Eukaryotic Genomes
      • In eukaryotes, the DNA-protein complex, called chromatin
        • Is ordered into higher structural levels than the DNA-protein complex in prokaryotes
      Figure 19.1
      • Chromatin structure is based on successive levels of DNA packing
      • Eukaryotic DNA
        • Is precisely combined with a large amount of protein
      • Eukaryotic chromosomes
        • Contain an enormous amount of DNA relative to their condensed length
    • Nucleosomes, or “Beads on a String”
      • Proteins called histones
        • Are responsible for the first level of DNA packing in chromatin
        • Bind tightly to DNA
      • The association of DNA and histones
        • Seems to remain intact throughout the cell cycle
      • In electron micrographs
        • Unfolded chromatin has the appearance of beads on a string
      • Each “bead” is a nucleosome
        • The basic unit of DNA packing
      Figure 19.2 a 2 nm 10 nm DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bad”) Histone H1 (a) Nucleosomes (10-nm fiber)
    • Higher Levels of DNA Packing
      • The next level of packing
        • Forms the 30-nm chromatin fiber
      Figure 19.2 b Nucleosome 30 nm (b) 30-nm fiber
      • The 30-nm fiber, in turn
        • Forms looped domains, making up a 300-nm fiber
      Figure 19.2 c Protein scaffold 300 nm (c) Looped domains (300-nm fiber) Loops Scaffold
      • In a mitotic chromosome
        • The looped domains themselves coil and fold forming the characteristic metaphase chromosome
      Figure 19.2 d 700 nm 1,400 nm (d) Metaphase chromosome
      • In interphase cells
        • Most chromatin is in the highly extended form called euchromatin
      • Gene expression can be regulated at any stage, but the key step is transcription
      • All organisms
        • Must regulate which genes are expressed at any given time
      • During development of a multicellular organism
        • Its cells undergo a process of specialization in form and function called cell differentiation
    • Differential Gene Expression
      • Each cell of a multicellular eukaryote
        • Expresses only a fraction of its genes
      • In each type of differentiated cell
        • A unique subset of genes is expressed
      Figure 19.3 Signal NUCLEUS Chromatin Chromatin modification: DNA unpacking involving histone acetylation and DNA demethlation Gene DNA Gene available for transcription RNA Exon Transcription Primary transcript RNA processing Transport to cytoplasm Intron Cap mRNA in nucleus Tail CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypetide Cleavage Chemical modification Transport to cellular destination Active protein Degradation of protein Degraded protein
    • Histone Modification
      • Chemical modification of histone tails
        • Can affect the configuration of chromatin and thus gene expression
      Figure 19.4a (a) Histone tails protrude outward from a nucleosome Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation DNA double helix Amino acids available for chemical modification Histone tails
      • Histone acetylation
        • Seems to loosen chromatin structure and thereby enhance transcription
      Figure 19.4 b (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones
    • Organization of a Typical Eukaryotic Gene
      • Associated with most eukaryotic genes are multiple control elements
        • Segments of noncoding DNA that help regulate transcription by binding certain proteins
      Figure 19.5 Enhancer (distal control elements) Proximal control elements DNA Upstream Promoter Exon Intron Exon Intron Poly-A signal sequence Exon Termination region Transcription Downstream Poly-A signal Exon Intron Exon Intron Exon Primary RNA transcript (pre-mRNA) 5 Intron RNA RNA processing: Cap and tail added; introns excised and exons spliced together Coding segment P P P G mRNA 5 Cap 5 UTR (untranslated region) Start codon Stop codon 3 UTR (untranslated region) Poly-A tail Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Cleared 3 end of primary transport
    • Enhancers and Specific Transcription Factors
      • Proximal control elements
        • Are located close to the promoter
      • Distal control elements, groups of which are called enhancers
        • May be far away from a gene or even in an intron
    • Video Clip
      • An activator
        • Is a protein that binds to an enhancer and stimulates transcription of a gene
      Figure 19.6 Distal control element Activators Enhancer Promoter Gene TATA box General transcription factors DNA-bending protein Group of Mediator proteins RNA Polymerase II RNA Polymerase II RNA synthesis Transcription Initiation complex Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation A DNA-bending protein brings the bound activators closer to the promoter. Other transcription factors, mediator proteins, and RNA polymerase are nearby. 2 Activator proteins bind to distal control elements grouped as an enhancer in the DNA. This enhancer has three binding sites. 1 The activators bind to certain general transcription factors and mediator proteins, helping them form an active transcription initiation complex on the promoter. 3
      • Some specific transcription factors function as repressors
        • To inhibit expression of a particular gene
      • Some activators and repressors
        • Act indirectly by influencing chromatin structure
    • Combinatorial Control of Gene Activation
      • A particular combination of control elements
        • Will be able to activate transcription only when the appropriate activator proteins are present
      Figure 19.7a, b Video Clip Enhancer Promoter Control elements Albumin gene Crystallin gene Liver cell nucleus Lens cell nucleus Available activators Available activators Albumin gene expressed Albumin gene not expressed Crystallin gene not expressed Crystallin gene expressed (a) (b) Liver cell Lens cell
      • Cancer results from genetic changes that affect cell cycle control
      • The gene regulation systems that go wrong during cancer
        • Turn out to be the very same systems that play important roles in embryonic development
    • Types of Genes Associated with Cancer
      • The genes that normally regulate cell growth and division during the cell cycle
        • Include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways
    • Oncogenes and Proto-Oncogenes
      • Oncogenes
        • Are cancer-causing genes
      • Proto-oncogenes
        • Are normal cellular genes that code for proteins that stimulate normal cell growth and division
      • A DNA change that makes a proto-oncogene excessively active
        • Converts it to an oncogene, which may promote excessive cell division and cancer
      Figure 19.11 Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls Gene amplification: multiple copies of the gene Point mutation within a control element Point mutation within the gene Oncogene Oncogene Normal growth-stimulating protein in excess Hyperactive or degradation- resistant protein Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess New promoter
      • The p53 gene encodes a tumor-suppressor protein
        • That is a specific transcription factor that promotes the synthesis of cell cycle–inhibiting proteins
      Figure 19.12b UV light DNA Defective or missing transcription factor, such as p53, cannot activate transcription MUTATION Protein that inhibits the cell cycle pathway, DNA damage is an intracellular signal that is passed via protein kinases and leads to activation of p53. Activated p53 promotes transcription of the gene for a protein that inhibits the cell cycle. The resulting suppression of cell division ensures that the damaged DNA is not replicated. Mutations causing deficiencies in any pathway component can contribute to the development of cancer. (b) Cell cycle–inhibiting pathway. In this 1 3 2 Protein kinases 2 3 Active form of p53 DNA damage in genome 1
      • Mutations that knock out the p53 gene
        • Can lead to excessive cell growth and cancer
      Figure 19.12c EFFECTS OF MUTATIONS Protein overexpressed Cell cycle overstimulated Increased cell division Cell cycle not inhibited Protein absent Effects of mutations. Increased cell division, possibly leading to cancer, can result if the cell cycle is overstimulated, as in (a), or not inhibited when it normally would be, as in (b). (c)
    • The Multistep Model of Cancer Development
      • Normal cells are converted to cancer cells
        • By the accumulation of multiple mutations affecting proto-oncogenes and tumor-suppressor genes
      • A multistep model for the development of colorectal cancer
      Figure 19.13 Colon Colon wall Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Malignant tumor (carcinoma) 2 Activation of ras oncogene 3 Loss of tumor- suppressor gene DCC 4 Loss of tumor-suppressor gene p53 5 Additional mutations 1 Loss of tumor- suppressor gene APC (or other)
      • Certain viruses
        • Promote cancer by integration of viral DNA into a cell’s genome
      • Individuals who inherit a mutant oncogene or tumor-suppressor allele
        • Have an increased risk of developing certain types of cancer
      • Eukaryotic genomes can have many noncoding DNA sequences in addition to genes
      • The bulk of most eukaryotic genomes
        • Consists of noncoding DNA sequences, often described in the past as “junk DNA”
      • However, much evidence is accumulating
        • That noncoding DNA plays important roles in the cell (Probably is no such thing as ‘junk DNA’)
    • The Relationship Between Genomic Composition and Organismal Complexity
      • Compared with prokaryotic genomes, the genomes of eukaryotes
        • Generally are larger
        • Have longer genes
        • Contain a much greater amount of noncoding DNA both associated with genes and between genes
    • Transposable Elements and Related Sequences
      • The first evidence for wandering DNA segments
        • Came from geneticist Barbara McClintock’s breeding experiments with Indian corn
      Figure 19.15
    • Movement of Transposons and Retrotransposons
      • Eukaryotic transposable elements are of two types
        • Transposons, which move within a genome by means of a DNA intermediate
        • Retrotransposons, which move by means of an RNA intermediate
      Figure 19.16a, b Transposon New copy of transposon Transposon is copied DNA of genome Insertion Mobile transposon (a) Transposon movement (“copy-and-paste” mechanism) Retrotransposon New copy of retrotransposon DNA of genome RNA Reverse transcriptase (b) Retrotransposon movement Insertion
    • Sequences Related to Transposable Elements
      • Multiple copies of transposable elements and sequences related to them
        • Are scattered throughout the eukaryotic genome
      • In humans
        • A large portion of transposable element–related DNA consists of a family of similar sequences called Alu elements
    • Other Repetitive DNA, Including Simple Sequence DNA
      • Simple sequence DNA
        • Contains many copies of tandemly repeated short sequences
        • Is common in centromeres and telomeres, where it probably plays structural roles in the chromosome
    • Genes and Multigene Families
      • Most eukaryotic genes
        • Are present in one copy per haploid set of chromosomes
      • The rest of the genome
        • Occurs in multigene families, collections of identical or very similar genes
      • Some multigene families
        • Consist of identical DNA sequences, usually clustered tandemly, such as those that code for RNA products
      Figure 19.17a Part of the ribosomal RNA gene family DNA RNA transcripts Non-transcribed spacer Transcription unit DNA 18S 5.8S 28S rRNA 5.8S 28S 18S
      • The classic examples of multigene families of nonidentical genes
        • Are two related families of genes that encode globins
      Figure 19.17b The human -globin and -globin gene families  -Globin Heme Hemoglobin  -Globin  -Globin gene family  -Globin gene family Chromosome 16 Chromosome 11 Embryo Fetus and adult Embryo Fetus Adult  G  A           2   1  2  1  
      • Duplications, rearrangements, and mutations of DNA contribute to genome evolution
      • The basis of change at the genomic level is mutation
        • Which underlies much of genome evolution
      Does the following produce new and novel information?
    • Duplication of Chromosome Sets
      • Accidents in cell division
        • Can lead to extra copies of all or part of a genome, which may then diverge if one set accumulates sequence changes
    • Duplication and Divergence of DNA Segments
      • Unequal crossing over during prophase I of meiosis
        • Can result in one chromosome with a deletion and another with a duplication of a particular gene
      Figure 19.18 Nonsister chromatids Transposable element Gene Incorrect pairing of two homologues during meiosis Crossover and
    • Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling
      • A particular exon within a gene
        • Could be duplicated on one chromosome and deleted from the homologous chromosome
      • In exon shuffling
        • Errors in meiotic recombination lead to the occasional mixing and matching of different exons either within a gene or between two nonallelic genes
      Figure 19.20 EGF EGF EGF EGF Epidermal growth factor gene with multiple EGF exons (green) F F F F Fibronectin gene with multiple “ finger” exons (orange) Exon shuffling Exon duplication Exon shuffling K F EGF K K Plasminogen gene with a “ kfingle” exon (blue) Portions of ancestral genes TPA gene as it exists today
    • How Transposable Elements Contribute to Genome Evolution
      • Movement of transposable elements or recombination between copies of the same element
        • Occasionally generates new sequence combinations that are beneficial to the organism (however, no new information was added)
      • Some mechanisms
        • Can alter the functions of genes or their patterns of expression and regulation