1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint TextEdit Art Slides for Biology, Seventh Edition Neil Campbell and Jane Reece Chapter 19 Eukaryotic Genomes Organization, Regulation, and Evolution

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.1 DNA in a eukaryotic chromosome from a developing salamander egg

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.2 Levels of chromatin packing 2 nm 10 nm DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bad”) Histone H1 (a) Nucleosomes (10-nm fiber) Nucleosome Protein scaffold 30 nm 300 nm 700 nm 1,400 nm (b) 30-nm fiber (c) Looped domains (300-nm fiber) (d) Metaphase chromosome Loops Scaffold

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.3 Stages in gene expression that can be regulated in eukaryotic cells 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

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.4 A simple model of histone tails and the effect of histone acetylation Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Histone tails DNA double helix Amino acids available for chemical modification (a) Histone tails protrude outward from a nucleosome (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.5 A eukaryotic gene and its transcript Enhancer (distal control elements) Proximal control elements DNA Upstream Promoter Exon IntronExon Intron Poly-A signal sequence Exon Termination region Transcription Downstream Poly-A signal ExonIntron Exon IntronExon 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

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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 synthesisTranscription 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 Figure 19.6 A model for the action of enhancers and transcription activators

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.7 Cell type–specific transcription 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 Liver cellLens cell (a) (b)

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.8 Alternative RNA splicing Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Exons DNA Primary RNA transcript mRNA RNA splicing or

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.9 Regulation of gene expression by microRNAs (miRNAs) Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Degradation of mRNA OR Blockage of translation Target mRNA miRNA Protein complex Dicer Hydrogen bond The micro- RNA (miRNA) precursor folds back on itself, held together by hydrogen bonds. 1 An enzyme called Dicer moves along the double- stranded RNA, cutting it into shorter segments. 2 One strand of each short double- stranded RNA is degraded; the other strand (miRNA) then associates with a complex of proteins. 3 The bound miRNA can base-pair with any target mRNA that contains the complementary sequence. 4 The miRNA-protein complex prevents gene expression either by degrading the target mRNA or by blocking its translation. 5

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.10 Degradation of a protein by a proteasome Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation Ubiquitin Protein to be degraded Ubiquinated protein Proteasome and ubiquitin to be recycled Protein fragments (peptides) Multiple ubiquitin mol- ecules are attached to a protein by enzymes in the cytosol. 1 The ubiquitin-tagged protein is recognized by a proteasome, which unfolds the protein and sequesters it within a central cavity. 2 Enzymatic components of the proteasome cut the protein into small peptides, which can be further degraded by other enzymes in the cytosol. 2 Protein entering a proteasome

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.11 Genetic changes that can turn proto-oncogenes into oncogenes 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 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

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.12 Signaling pathways that regulate cell division MUTATION 1 Growth factor 2 Receptor p p p p p p GTP Ras 3 G protein Ras GTP Hyperactive Ras protein (product of oncogene) issues signals on its own 4 Protein kinases (phosphorylation cascade) 5 Transcription factor (activator) NUCLEUS DNA Gene expression Protein that stimulates the cell cycle 2 Protein kinases UV light DNA damage in genome 1 DNA 3 Active form of p53 Defective or missing transcription factor, such as p53, cannot activate transcription MUTATION Protein that inhibits the cell cycle EFFECTS OF MUTATIONS Protein overexpressed Cell cycle overstimulated Increased cell division Cell cycle not inhibited Protein absent (a) Cell cycle–stimulating pathway. This pathway is triggered by a growth factor that binds to its receptor in the plasma membrane. The signal is relayed to a G protein called Ras. Like all G proteins, Ras is active when GTP is bound to it. Ras passes the signal to a series of protein kinases. The last kinase activates a transcription activator that turns on one or more genes for proteins that stimulate the cell cycle. If a mutation makes Ras or any other pathway component abnormally active, excessive cell division and cancer may result. 1 2 4 3 5 (b) Cell cycle–inhibiting pathway. In this 2 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. 1 3 (c) 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).

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Colon 1 Loss of tumor-suppressor gene APC (or other) 2 Activation of Ras oncogene 3 Loss of tumor- suppressor gene DCC 4 Loss of tumor-suppressor gene p53 5 Additional mutations Colon wall Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Malignant tumor (carcinoma) Figure 19.13 A multistep model for the development of colorectal cancer

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.14 Types of DNA sequences in the human genome Exons (regions of genes coding for protein, rRNA, tRNA) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory sequences (24%) Unique noncoding DNA (15%) Repetitive DNA unrelated to transposable elements (about 15%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%)

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.15 The effect of transposable elements on corn kernel color

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.16 Movement of eukaryotic transposable elements 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

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.17 Gene families DNA RNA transcripts Non-transcribed spacer Transcription unit DNA 18S 5.8S 28S rRNA 5.8S (a) Part of the ribosomal RNA gene family 28S 18S Heme Hemoglobin  -Globin  -Globin  -Globin gene family  -Globin gene family Chromosome 16 Chromosome 11     22  11 22 11   GG AA    Embryo Fetus and adult Embryo Fetus Adult (b) The human  -globin and  -globin gene families

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.18 Gene duplication due to unequal crossing over Nonsister chromatids Transposable element Gene Incorrect pairing of two homologues during meiosis Crossover and

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.19 Evolution of the human  -globin and  -globin gene families Ancestral globin gene          22  11 22 11   GG AA    -Globin gene family on chromosome 16  -Globin gene family on chromosome 11   Evolutionary time Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Table 19.1 Percentage of Similarity in Amino Acid Sequence Between Human Globin Proteins

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 19.20 Evolution of a new gene by exon shuffling 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 FEGFK K Plasminogen gene with a “kringle” exon (blue) Portions of ancestral genes TPA gene as it exists today