Copyright © 2009 Pearson Education, Inc. PowerPoint Lectures for Biology: Concepts & Connections, Sixth Edition Campbell, Reece, Taylor, Simon, and Dickey Chapter 11 How Genes Are Controlled 0 Lecture by Mary C. Colavito

11.2 Differentiation results from the expression of different combinations of genes  Differentiation involves cell specialization, in both structure and function  Differentiation is controlled by turning specific sets of genes on or off 0 Copyright © 2009 Pearson Education, Inc.

0 Muscle cell Pancreas cells Blood cells

0 Muscle cell

0 Pancreas cells

0 Blood cells

11.3 DNA packing in eukaryotic chromosomes helps regulate gene expression  Eukaryotic chromosomes undergo multiple levels of folding and coiling, called DNA packing –Nucleosomes are formed when DNA is wrapped around histone proteins –“Beads on a string” appearance –Each bead includes DNA plus 8 histone molecules –String is the linker DNA that connects nucleosomes –Tight helical fiber is a coiling of the nucleosome string –Supercoil is a coiling of the tight helical fiber –Metaphase chromosome represents the highest level of packing  DNA packing can prevent transcription 0 Copyright © 2009 Pearson Education, Inc.

11.3 DNA packing in eukaryotic chromosomes helps regulate gene expression 0 Copyright © 2009 Pearson Education, Inc. Animation: DNA Packing

0 DNA double helix (2-nm diameter) “Beads on a string” Linker Histones Metaphase chromosome Tight helical fiber (30-nm diameter) Nucleosome (10-nm diameter) Supercoil (300-nm diameter) 700 nm

11.4 In female mammals, one X chromosome is inactive in each somatic cell  X-chromosome inactivation –In female mammals, one of the two X chromosomes is highly compacted and transcriptionally inactive –Random inactivation of either the maternal or paternal chromosome –Occurs early in embryonic development and all cellular descendants have the same inactivated chromosome –Inactivated X chromosome is called a Barr body –Tortoiseshell fur coloration is due to inactivation of X chromosomes in heterozygous female cats 0 Copyright © 2009 Pearson Education, Inc.

0 Two cell populations in adult X chromosomes Early embryo Allele for black fur Inactive X Black fur Allele for orange fur Orange fur Cell division and random X chromosome inactivation Active X Inactive X Active X

11.5 Complex assemblies of proteins control eukaryotic transcription  Eukaryotic genes –Each gene has its own promoter and terminator –Are usually switched off and require activators to be turned on –Are controlled by interactions between numerous regulatory proteins and control sequences 0 Copyright © 2009 Pearson Education, Inc.

11.5 Complex assemblies of proteins control eukaryotic transcription  Regulatory proteins that bind to control sequences –Transcription factors promote RNA polymerase binding to the promoter –Activator proteins bind to DNA enhancers and interact with other transcription factors –Silencers are repressors that inhibit transcription  Control sequences –Promoter –Enhancer –Related genes located on different chromosomes can be controlled by similar enhancer sequences 0 Copyright © 2009 Pearson Education, Inc.

11.5 Complex assemblies of proteins control eukaryotic transcription 0 Copyright © 2009 Pearson Education, Inc. Animation: Initiation of Transcription

0 Enhancers Other proteins DNA Transcription factors Activator proteins RNA polymerase Promoter Gene Bending of DNA Transcription

11.8 Translation and later stages of gene expression are also subject to regulation  Control of gene expression also occurs with –Breakdown of mRNA –Initiation of translation –Protein activation –Protein breakdown 0 Copyright © 2009 Pearson Education, Inc.

0 Folding of polypeptide and formation of S—S linkages Initial polypeptide (inactive) Folded polypeptide (inactive) Active form of insulin Cleavage

11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes  Many possible control points exist; a given gene may be subject to only a few of these –Chromosome changes (1) –DNA unpacking –Control of transcription (2) –Regulatory proteins and control sequences –Control of RNA processing –Addition of 5’ cap and 3’ poly-A tail (3) –Splicing (4) –Flow through nuclear envelope (5) 0 Copyright © 2009 Pearson Education, Inc.

11.9 Review: Multiple mechanisms regulate gene expression in eukaryotes  Many possible control points exist; a given gene may be subject to only a few of these –Breakdown of mRNA (6) –Control of translation (7) –Control after translation –Cleavage/modification/activation of proteins (8) –Breakdown of protein (9) 0 Copyright © 2009 Pearson Education, Inc.

 Applying Your Knowledge For each of the following, determine whether an increase or decrease in the amount of gene product is expected –The mRNA fails to receive a poly-A tail during processing in the nucleus –The mRNA becomes more stable and lasts twice as long in the cell cytoplasm –The region of the chromatin containing the gene becomes tightly compacted –An enzyme required to cleave and activate the protein product is missing 0 Copyright © 2009 Pearson Education, Inc Review: Multiple mechanisms regulate gene expression in eukaryotes

0 Copyright © 2009 Pearson Education, Inc Review: Multiple mechanisms regulate gene expression in eukaryotes Animation: Protein Processing Animation: Protein Degradation

0 NUCLEUS DNA unpacking Other changes to DNA Addition of cap and tail Chromosome Gene RNA transcript Gene Transcription Intron Exon Splicing Cap mRNA in nucleus Tail Flow through nuclear envelope Broken- down mRNA CYTOPLASM Breakdown of mRNA Translation mRNA in cytoplasm Broken- down protein Cleavage / modification / activation Breakdown of protein Polypeptide Active protein

NUCLEUS DNA unpacking Other changes to DNA Addition of cap and tail Chromosome Gene RNA transcript Gene Transcription Intron Exon Splicing Cap mRNA in nucleus Tail Flow through nuclear envelope

Broken- down mRNA CYTOPLASM Breakdown of mRNA Translation mRNA in cytoplasm Broken- down protein Cleavage / modification / activation Breakdown of protein Polypeptide Active protein

Animation: Development of Head-Tail Axis in Fruit Flies Cascades of gene expression direct the development of an animal 0 Copyright © 2009 Pearson Education, Inc. Animation: Cell Signaling

11.12 Signal transduction pathways convert messages received at the cell surface to responses within the cell  Signal transduction pathway is a series of molecular changes that converts a signal at the cell’s surface to a response within the cell –Signal molecule is released by a signaling cell –Signal molecule binds to a receptor on the surface of a target cell 0 Copyright © 2009 Pearson Education, Inc.

11.12 Signal transduction pathways convert messages received at the cell surface to responses within the cell –Relay proteins are activated in a series of reactions –A transcription factor is activated and enters the nucleus –Specific genes are transcribed to initiate a cellular response 0 Copyright © 2009 Pearson Education, Inc. Animation: Signal Transduction Pathways Animation: Overview of Cell Signaling

0 Signaling cell DNA Nucleus Transcription factor (activated) Signaling molecule Plasma membrane Receptor protein Relay proteins Transcription mRNA New protein Translation Target cell

THE GENETIC BASIS OF CANCER Copyright © 2009 Pearson Education, Inc.

11.18 Cancer results from mutations in genes that control cell division  Mutations in two types of genes can cause cancer –Oncogenes –Proto-oncogenes normally promote cell division –Mutations to oncogenes enhance activity –Tumor-suppressor genes –Normally inhibit cell division –Mutations inactivate the genes and allow uncontrolled division to occur 0 Copyright © 2009 Pearson Education, Inc.

11.18 Cancer results from mutations in genes that control cell division  Oncogenes –Promote cancer when present in a single copy –Can be viral genes inserted into host chromosomes –Can be mutated versions of proto-oncogenes, normal genes that promote cell division and differentiation –Converting a proto-oncogene to an oncogene can occur by –Mutation causing increased protein activity –Increased number of gene copies causing more protein to be produced –Change in location putting the gene under control of new promoter for increased transcription 0 Copyright © 2009 Pearson Education, Inc.

11.18 Cancer results from mutations in genes that control cell division  Tumor-suppressor genes –Promote cancer when both copies are mutated 0 Copyright © 2009 Pearson Education, Inc.

0 Mutation within the gene Hyperactive growth- stimulating protein in normal amount Proto-oncogene DNA Multiple copies of the gene Gene moved to new DNA locus, under new controls Oncogene New promoter Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess

0 Mutated tumor-suppressor gene Tumor-suppressor gene Defective, nonfunctioning protein Normal growth- inhibiting protein Cell division under control Cell division not under control

11.19 Multiple genetic changes underlie the development of cancer  Four or more somatic mutations are usually required to produce a cancer cell  One possible scenario for colorectal cancer includes –Activation of an oncogene increases cell division –Inactivation of tumor suppressor gene causes formation of a benign tumor –Additional mutations lead to a malignant tumor 0 Copyright © 2009 Pearson Education, Inc.

0 1 Colon wall Cellular changes: DNA changes: Oncogene activated Increased cell division Tumor-suppressor gene inactivated Growth of polyp Second tumor- suppressor gene inactivated Growth of malignant tumor (carcinoma) 2 3

0 Chromosomes 1 mutation Normal cell 4 mutations 3 mutations 2 mutations Malignant cell

11.20 Faulty proteins can interfere with normal signal transduction pathways  Path producing a product that stimulates cell division  Product of ras proto-oncogene relays a signal when growth hormone binds to receptor  Product of ras oncogene relays the signal in the absence of hormone binding, leading to uncontrolled growth 0 Copyright © 2009 Pearson Education, Inc.

11.20 Faulty proteins can interfere with normal signal transduction pathways  Path producing a product that inhibits cell division –Product of p53 tumor-suppressor gene is a transcription factor –p53 transcription factor normally activates genes for factors that stop cell division –In the absence of functional p53, cell division continues because the inhibitory protein is not produced 0 Copyright © 2009 Pearson Education, Inc.

0 Growth factor Protein that Stimulates cell division Translation Nucleus DNA Target cell Normal product of ras gene Receptor Relay proteins Transcription factor (activated) Hyperactive relay protein (product of ras oncogene) issues signals on its own Transcription

0 Growth-inhibiting factor Protein that inhibits cell division Translation Normal product of p53 gene Receptor Relay proteins Transcription factor (activated) Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription Transcription Protein absent (cell division not inhibited)

11.21 CONNECTION: Lifestyle choices can reduce the risk of cancer  Carcinogens are cancer-causing agents that damage DNA and promote cell division –X-rays and ultraviolet radiation –Tobacco  Healthy lifestyle choices –Avoiding carcinogens –Avoiding fat and including foods with fiber and antioxidants –Regular medical checkups 0 Copyright © 2009 Pearson Education, Inc.

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0 Nucleus from donor cell Early embryo resulting from nuclear trans- plantation Surrogate mother Clone of donor

0 Nucleus from donor cell Early embryo resulting from nuclear trans- plantation Embryonic stem cells in culture Specialized cells

1. Describe the control points in expression of a eukaryotic gen e 2. Describe DNA packing and explain how it is related to gene expression 3. Explain how alternative RNA splicing and microRNAs affect gene expression 4. Compare and contrast the control mechanisms for prokaryotic and eukaryotic genes 0 You should now be able to Copyright © 2009 Pearson Education, Inc.

1.Distinguish between terms in the following groups: promoter—operator; oncogene—tumor suppressor gene; reproductive cloning— therapeutic cloning 2.Define the following terms: Barr body, carcinogen, DNA microarray, homeotic gene; stem cell; X-chromosome inactivation 3.Describe the process of signal transduction, explain how it relates to yeast mating, and explain how it is disrupted in cancer development 0 You should now be able to Copyright © 2009 Pearson Education, Inc.

1.Explain how cascades of gene expression affect development 2.Compare and contrast techniques of plant and animal cloning 3.Describe the types of mutations that can lead to cancer 4.Identify lifestyle choices that can reduce cancer risk 0 You should now be able to Copyright © 2009 Pearson Education, Inc.