Chapter 11 How Genes Are Controlled Power Point

Chapter 11 How Genes Are Controlled Power. Point® Lectures created by Edward J. Zalisko for Campbell Essential Biology, Sixth Edition, and Campbell Essential Biology with Physiology, Fifth Edition – Eric J. Simon, Jean L. Dickey, Kelly A. Hogan, and Jane B. Reece © 2016 Pearson Education, Inc.

Why Gene Regulation Matters Figure 11. 0 -1 © 2016 Pearson Education, Inc.

Biology and Society: Tobacco’s Smoking Gun • During the 1900 s, doctors noticed that • smoking increased and lung cancer increased. • European explorers brought back tobacco, (trade item among Native Americans) when they returned from their first voyages. • Smoking increased in popularity, and by the 1950 s, about half of all Americans smoked more than a pack of cigarettes each day. • By the mid-20 th century, doctors notice the rate of lung cancer had increased dramatically. • By 1990, lung cancer was killing more than twice as many men each year as any other type of cancer. • But a few vocal skeptics, mostly tied to groups with an economic interest in the tobacco industry, doubted the link between smoking and cancer.

Biology and Society: Tobacco’s Smoking Gun • The “smoking gun” was found in 1996, when researchers added BPDE (a component of tobacco smoke) to human lung cells growing in the lab. • They showed that BPDE binds to a gene cells called p 53 that codes for a protein that helps suppress the formation of tumors. • BPDE causes mutations in the p 53 gene that deactivate the protein. • With this important tumor-suppressor protein deactivated, tumors grow. • How can a mutation in a gene lead to cancer? • It turns out that many cancer-associated genes encode proteins that turn other genes on or off. • When these proteins malfunction, the cell may become cancerous.

Chapter Thread: Cancer © 2016 Pearson Education, Inc. Figure 11. 0 -2

HOW AND WHY GENES ARE REGULATED • Every somatic cell in an organism contains identical genetic instructions: they all share the same genome, so what makes them different? • If every cell contains identical genetic instructions, How do cells become different from one another? • Individual cell must undergo cellular differentiation, where cells become specialized in Structure and Function • Every cell must have its own structure and function which differentiates them from others • Control mechanism must turn on certain genes while other genes remain turned of in a particular cell. This is called gene regulation, the turning on and off of genes. © 2016 Pearson Education, Inc.

HOW AND WHY GENES ARE REGULATED • What does it mean to say that genes are turned on or off? • Genes determine the nucleotide sequence of specific m. RNA molecules, and m. RNA in turn determines the sequence of amino acids in proteins (DNA → RNA → protein). • A gene that is turned on is being transcribed into m. RNA, and that message is being translated into specific proteins. • The overall process by which genetic information flows from genes to proteins is called gene expression. • All the different cells that contain the same genes differentiate themselves by the selective expression of genes that is, from the pattern of genes turned on in a given cell at a given time. üTherefore, the great differences among cells in an organism must result from the selective expression of genes.

HOW AND WHY GENES ARE REGULATED • Figure 11. 1 shows the patterns of gene expression for four genes in three different specialized cells of an adult human. • Note that the genes for “housekeeping” enzymes, such as those that provide energy via glycolysis, are “on” in all the cells. • In contrast, the genes for some proteins, such as insulin and hemoglobin, are expressed only by particular kinds of cells. • One protein, hemoglobin, is not expressed in any of the cell types shown in the figure. © 2016 Pearson Education, Inc.

Pancreas cell Colorized TEM Colorized SEM Colorized TEM Patterns of gene expression in three types of human cells White blood cell Nerve cell Gene for a glycolysis enzyme Antibody gene Insulin gene Hemoglobin gene © 2016 Pearson Education, Inc. Figure 11. 1

Gene Regulation in Bacteria • Natural selection has favored bacteria that express only the genes whose products are needed by the cell. So how do bacteria selectively turn their genes on and off? • Imagine an Escherichia coli bacterium living in your intestines. • If you drink a milk shake, there will be a sudden rush of the sugar lactose. • In response, E. coli will express three genes for enzymes that enable the bacterium to absorb and digest this sugar. • After the lactose is gone, these genes are turned off. • The Lac Operon, is a gene system characterized in E-coli for the regulation of the gene of utilization of lactose.

Gene Regulation in Bacteria • An operon includes • a cluster of genes with related functions • the control sequences that turn the genes on or off • The bacterium E. coli used the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment. 1. If lactose is absent the gene is turned off. 2. If lactose is present, the gene is turned on.

Gene Regulation in Bacteria • How do DNA control sequences turn genes on or off? The lac operon uses • A promoter, a control sequence where the RNA polymerase attaches and initiates transcription • Between promoter and genes is an operator, a DNA segment that acts as a switch that is turned on or off • A repressor, which binds to the operator and physically blocks the attachment of RNA polymerase is synthetize by the Regulatory gene • The operator and repressor together determine whether RNA polymerase can attach to the promoter and start transcribing the genes. • In the lac operon, when the operator switch is turned on, all the enzymes needed to metabolize lactose are made at once.

How do DNA control sequence turn genes on or off? Operon Genes for lactose enzymes Operator Regulatory Promoter gene DNA 1 m. RNA 2 RNA polymerase cannot attach to promoter Active repressor Protein Operon turned off (lactose absent) Transcription DNA 3 m. RNA 2 Protein 1 Lactose RNA polymerase bound to promoter Translation m. RNA Inactive repressor Lactose enzymes © 2016 Pearson Education, Inc. Operon turned on (lactose inactivates repressor) Figure 11. 2

the lac operon in “off” mode, its status when there is no lactose available. Transcription is turned off because a protein called a repressor ü binds to the operator and ü physically blocks the attachment of RNA polymerase to the promoter. Operon Operator Regulatory Promoter gene Genes for lactose enzymes DNA m. RNA 1 Protein Active repressor Operon turned off (lactose absent) © 2016 Pearson Education, Inc. 2 RNA polymerase cannot attach to promoter Figure 11. 2 -1

the operon in “on” mode, when lactose is present. The lactose interferes with attachment of the lac repressor to the operator by ü binding to the repressor and changing the repressor’s shape so that repressor cannot bind to operator, and operator switch remains on. ü RNA polymerase is no longer blocked and can now bind to the promoter and transcribe genes for the lactose enzymes into m. RNA. ü Translation produces all three lactose enzymes. Transcription DNA 3 m. RNA 2 Protein 1 Lactose RNA polymerase bound to promoter m. RNA Translation Inactive repressor Lactose enzymes Operon turned on (lactose inactivates repressor) © 2016 Pearson Education, Inc.

Gene Regulation in Eukaryotic Cells • Eukaryotes cells, have more sophisticated mechanisms than bacteria for regulating the expression of their genes. • The pathway from gene (chromosome) to an active protein is a long one, providing a number of points where the process can be regulated (turned on or off, speeded up or slowed down). • The flow of genetic information from a eukaryotic chromosome to an active protein can be illustrated by this analogy to a water supply system with many control valves along the way. • Starting with the water from the reservoir of genetic information (chromosome) to the faucets at our kitchen sink (active protein) • At various points, valves control the flow of water. • We use this analogy in Figure 11. 3 to illustrate the flow of genetic information from

The gene expression “pipeline” in a eukaryotic cell Chromosome Unpacking of DNA Gene Transcription of gene Intron Processing of RNA Flow of m. RNA through nuclear envelope Exon RNA transcript Cap Tail m. RNA in nucleus m. RNA in cytoplasm Nucleus Cytoplasm Breakdown of m. RNA Translation of m. RNA Polypeptide Various changes to polypeptide Active protein Breakdown of protein

Figure 11. 3 -1 Chromosome Unpacking of DNA Gene Transcription of gene Intron Exon RNA transcript © 2016 Pearson Education, Inc.

Figure 11. 3 -2 Processing of RNA Flow of m. RNA through Cap nuclear Tail envelope m. RNA in nucleus Nucleus Cytoplasm m. RNA in cytoplasm Breakdown of m. RNA © 2016 Pearson Education, Inc.

Figure 11. 3 -3 Translation of m. RNA Polypeptide Various changes to polypeptide Breakdown of protein Active protein © 2016 Pearson Education, Inc.

The Regulation of DNA Packing • DNA packing tends to prevent gene expression by preventing RNA polymerase and other transcription proteins from binding to DNA • Cells may use DNA packing for long-term inactivation of genes. • X chromosome inactivation • Occurs in female mammals • first takes place early in embryonic development, when one of the two X chromosomes in each cell is inactivated at random • All of the descendants will have the same X chromosome turned off. © 2016 Pearson Education, Inc.

X chromosome inactivation: the tortoiseshell pattern on a cat If a female cat is has different versions of a gene (heterozygous) for a gene on the X chromosome • About half her cells will express one allele • The others will express the alternate allele Two cell populations in adult cat: Early embryo: X chromosomes Allele for orange fur Cell division and X chromosome inactivation Allele for black fur © 2016 Pearson Education, Inc. Active X Inactive X Active X Orange fur Black fur

The Initiation of Transcription • The initiation of transcription is the most important stage for regulating gene expression. • In prokaryotes and eukaryotes, regulatory proteins • bind to DNA and • turn the transcription of genes on and off. © 2016 Pearson Education, Inc.

The Initiation of Transcription • As illustrated in Figure 11. 5; • Unlike prokaryotic genes, transcriptional regulation in eukaryotes is complex typically involving many proteins, called transcription factors, that bind to DNA sequences called enhancers and promoter Enhancers (DNA control sequences) RNA polymerase Bend in the DNA Transcription factor Promoter Gene Transcription

The Initiation of Transcription • The DNA protein assembly promotes the binding of RNA polymerase to promoters. • Repressor proteins called silencers • may bind to DNA • inhibit the start of transcription • Activators are • more typically used by eukaryotes • turn genes on by binding to DNA • they make it easier for RNA polymerase to bind to the promoters • The “default” state for most genes in eukaryotes seems to be off, except for “housekeeping” genes for routine activities such as the digestion of glucose.

Animation: Initiation of Transcription © 2016 Pearson Education, Inc.

RNA Processing and Breakdown • Within a eukaryotic cell, transcription occurs in the nucleus, where RNA transcripts are processed into m. RNA before moving to the cytoplasm for translation by the ribosomes. • RNA processing includes the 1. addition of a cap and tail, 2. removal of any introns, and 3. splicing together of the remaining exons. • Exon splicing can occur in more than one way, generating different m. RNA molecules from the same starting RNA molecule. • With this sort of alternative RNA splicing, an organism can produce more than one type of polypeptide from a single

RNA Processing and Breakdown • In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene. • Eukaryotic m. RNAs can last for hours to weeks to months and are all eventually broken down and their parts recycled Exons 1 DNA RNA transcript 2 RNA splicing m. RNA 1 2 3 5 4 3 2 1 4 3 5 or 5 1 2 4 5

RNA Processing and Breakdown • After an m. RNA is produced in its final form, its “lifetime” can be highly variable, from hours to weeks to months. • Controlling the timing of m. RNA breakdown provides another opportunity for regulation. • But all m. RNAs are eventually broken down and their parts recycled. • Small single-stranded RNA molecules, called micro. RNAs (mi. RNAs), bind to complementary sequences on m. RNA molecules in the cytoplasm, • Some trigger the breakdown of their target m. RNA, and • others block translation • It has been estimated that mi. RNAs may regulate the expression of up to one-third of all human genes, a striking figure given that mi. RNA were unknown 20 years ago

Animation: RNA Processing © 2016 Pearson Education, Inc.

Animation: Blocking Translation © 2016 Pearson Education, Inc.

Animation: m. RNA Degradation © 2016 Pearson Education, Inc.

The Initiation of Translation • The process of translation offers additional opportunities for control by regulatory molecules. Protein Activation and Breakdown • The final opportunities for regulating gene expression occur after translation. • For example, the hormone insulin is synthesized as one long, inactive polypeptide that must be chopped into pieces before it comes active. • Other proteins require chemical modification before they become active. • The selective breakdown of proteins is another control mechanism operating after translation.

The formation of an active insulin molecule In this picture, the right side is an initial polypeptide (inactive) after it's cut it become an insulin (active hormone)

Animation: Protein Processing © 2016 Pearson Education, Inc.

Animation: Protein Degradation © 2016 Pearson Education, Inc.

Information Flow: Cell Signaling • In a multicellular organism, gene regulation can cross cell boundaries, allowing information to be communicated between and among cells. • A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell. • Within a cell, a signal molecule can act by binding to a receptor protein and initiating a signal transduction pathway, a series of molecular changes that converts a signal received outside a cell to a specific response inside the target cell

SIGNALING CELL 1 Plasma membrane Cell-signaling pathway that turns on a gene 4 TARGET CELL 2 Signal molecule 3 Receptor protein Relay proteins Transcription factor (activated) Nucleus Transcription 5 New protein m. RNA 6 Translation © 2016 Pearson Education, Inc. Figure 11. 8

Animation: Cell Signaling © 2016 Pearson Education, Inc.

Homeotic Genes • Master control genes called homeotic genes regulate groups of other genes that determine what body parts will develop in which locations. • Mutations in homeotic genes can produce bizarre effects. For example, fruit flies with mutations in homeotic genes may have extra sets of legs growing from their head (Figure 11. 9). Normal head due to presence of normal homeotic gene Normal fruit fly Mutant fly with extra wings Head with extra legs growing due to presence of mutant homeotic gene

Homeotic genes in two different animals Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism examined so far, including yeasts, plants, earthworms, frogs, chickens, mice, and humans. Fruit fly chromosome Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Adult fruit fly Adult mouse

DNA Microarrays: Visualizing Gene Expression • Scientists who study gene regulation often want to determine which genes are switched on or off in a particular cell. • A DNA microarray is a glass slide with thousands of different kinds of single-stranded DNA fragments attached to wells in a tightly spaced array (grid) to allows visualization of gene expression. • Complementary DNA (c. DNA) is synthesized using nucleotides that have been modified to fluoresce (glow) • The pattern of glowing spots enables the researcher to determine which genes were being transcribed in the starting cells. • Researchers can thus learn which genes are active in different tissues or in tissues from individuals in different states of health

Visualizing gene expression using a DNA microarray 1 m. RNA isolated Reverse transcriptase combined with fluorescent DNA nucleotides 2 c. DNA made from m. RNA 3 c. DNA mixture Fluorescent c. DNA microarray (each spot contains DNA from a particular gene) added to spots 4 Unbound c. DNA rinsed away Nonfluorescent spot Fluorescent c. DNA microarray (6, 400 genes) © 2016 Pearson Education, Inc. Figure 11. 10 DNA of an expressed gene unexpressed gene

Cloning Plants and Animals : The Genetic Potential of Cells • Gene regulation affects two important processes: 1. cloning and 2. cancer. • All body cells contain a complete complement of genes, even if they are not expressing all of them. • Differentiated cells • All contain a complete genome • Have the potential to express all of an organism’s genes • A single differentiated plant cell can undergo cell division and give rise to a complete adult plant. • The technique described in Figure 11. 11 can be used to produce hundreds or thousands of genetically identical organisms—clones— from the cells of a single plant

Test-tube cloning of an orchid Single cell Cells removed from orchid plant © 2016 Pearson Education, Inc. Cells in growth Cell division in culture medium Young plant Adult plant Figure 11. 11

The Genetic Potential of Cells • Plant cloning is now used extensively in agriculture. • Demonstrates that cell differentiation in plants does not cause irreversible changes in the DNA • For some plants, such as orchids, cloning is the only commercially practical means of reproducing plants. • In other cases, cloning has been used to reproduce a plant with specific desirable traits, such as high fruit yield or resistance to disease. • Seedless plants (such as seedless grapes, watermelons, and oranges) cannot reproduce sexually, leaving cloning as the sole means of massproducing these common foods.

The Genetic Potential of Cells • Regeneration is the regrowth of lost body parts. • When a salamander loses a leg, certain cells in the leg stump reverse their differentiated state, divide, and then differentiate again to give rise to a new leg. • Many other animals, especially among the invertebrates, can regenerate lost parts. • Isolated pieces of a few relatively simple animals can dedifferentiate and then develop into an entirely new organism.

Reproductive Cloning of Animals • Nuclear transplantation üInvolves replacing nuclei of egg cells with nuclei from differentiated cells üHas been used to clone a variety of animals • In 1997, Scottish researchers produced Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell in a procedure called reproductive cloning, because it results in the birth of a new animal.

Cloning by nuclear transplantation Reproductive cloning Donor cell Nucleus from donor cell Implant embryo in surrogate mother Clone of donor is born Therapeutic cloning Remove nucleus from egg cell Add somatic cell from adult donor © 2016 Pearson Education, Inc. Figure 11. 12 Grow in culture to produce a ball of cells Remove embryonic stem cells from embryo and grow in culture Induce stem cells to form specialized cells for therapeutic use

Reproductive Cloning of Animals • In 1996, researchers used reproductive cloning to produce the first mammal cloned from an adult cell, a sheep named Dolly. • The researchers fused specially treated sheep cells with eggs from which they had removed the nuclei. • After several days of growth, the resulting embryos were implanted in the uteruses of surrogate mothers. • One of the embryos developed into Dolly—and as expected, Dolly resembled the nucleus donor, not the egg donor or the surrogate mother.

Practical Applications of Reproductive Cloning • Since the first success in 1996, researchers have cloned many species of mammals, including mice, horses, dogs, mules, cows, pigs, rabbits, ferrets, camels, goats, and cats. (a) The first clone (b) Cloning for medical use (c) Clones of endangered animals Mouflon lamb with mother Banteng Gaur Figure 11. 13

Practical Applications of Reproductive Cloning • Why is reproductive cloning used? • In agriculture, farm animals with specific sets of desirable traits might be cloned to produce identical herds. • In research, genetically identical animals can provide perfect “control animals” for experiments. • Reproductive cloning is used to restock populations of endangered animals.

Practical Applications of Reproductive Cloning • Cloning may also create new problems. • Conservationists argue that cloning • may detract from efforts to preserve natural habitats. • does not increase genetic diversity, and • is therefore not as beneficial to endangered species as natural reproduction. • An increasing body of evidence suggests that cloned animals are less healthy than animals produced via fertilization.

Human Cloning • The cloning of various mammals has heightened speculation that humans could be cloned. • Critics point out the many practical and ethical objections to human cloning. • Practically, cloning of mammals is extremely difficult and inefficient. • Only a small percentage of cloned embryos develop normally and • they appear less healthy than naturally born kin.

Therapeutic Cloning and Stem Cells • The purpose of therapeutic cloning is not to produce a living organism but rather to produce embryonic stem cells.

Embryonic Stem Cells • In mammals, embryonic stem cells (ES cells) are obtained by • removing cells from an early embryo and • growing them in laboratory culture. • Embryonic stem cells can divide indefinitely and, under the right conditions, can (hypothetically) develop into a wide variety of different specialized cells. • If scientists can discover the right conditions, they may be able to grow cells for the repair of injured or diseased organs.

Differentiation of embryonic stem cells in culture Adult stem cells in bone marrow Embryonic stem cells in early embryo Blood cells Nerve cells Cultured embryonic stem cells Heart muscle cells Different culture conditions Figure 11. 14 © 2016 Pearson Education, Inc. Different types of differentiated cells

Umbilical Cord Blood Banking • Another source of stem cells is blood collected from the umbilical cord and placenta at birth. • Cord blood stem cells appeared to cure some babies of Krabbe’s disease, a fatal inherited disorder of the nervous system, and have been used as a treatment for leukemia. • To date, however, most attempts at umbilical cord blood therapy have not been successful. • At present, the American Academy of Pediatrics recommends cord blood banking only for babies born into families with a known genetic risk.

© 2016 Pearson Education, Inc. Figure 11. 15

Adult Stem Cells • Unlike embryonic ES cells, Adult stem cells are cells in adult tissues • are further along the road to differentiation than ES cells, • can therefore give rise to only a few related types of specialized cells, and • can also generate replacements for some of the body’s cells. • Because no embryonic tissue is involved in their harvest, adult stem cells are less ethically problematic than ES cells. © 2016 Pearson Education, Inc.

The Genetic Basis of Cancer • Cancer includes a variety of diseases in which cells escape from the control mechanisms that normally limit their growth and division. • This escape involves changes in gene expression. • One of the earliest clues to the role of genes in cancer was the discovery in 1911 of a virus that causes cancer in chickens. • Viruses that cause cancer can become permanent residents in host cells by inserting their nucleic acid into the DNA of host chromosomes.

Oncogenes and Tumor-Suppressor Genes • A gene that causes cancer is called an oncogene. • A cell can acquire an oncogene from • a virus or • the mutation of one of its own proto-oncogenes. • A normal gene with the potential to become an oncogene is called a proto-oncogene. • Many proto-oncogenes code for growth factors, proteins that stimulate cell division, or for other proteins that affect the cell cycle. • When they malfunction, cancer (uncontrolled cell growth) may result.

Oncogenes and Tumor-Suppressor Genes • For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA. • Figure 11. 16 illustrates three kinds of changes in DNA that can produce active oncogenes. In all three cases, abnormal gene expression stimulates the cell to divide excessively. © 2016 Pearson Education, Inc.

How a proto-oncogene can become an oncogene Proto-oncogene DNA Mutation within the gene Oncogene Hyperactive growth-stimulating protein © 2016 Pearson Education, Inc. Multiple copies of the gene Gene moved to new DNA position, under new controls New promoter Normal growth-stimulating protein in excess Figure 11. 16

Oncogenes and Tumor-Suppressor Genes • Changes in genes whose products inhibit cell division are also involved in cancer. • These genes are called tumor-suppressor genes because the proteins they encode normally help prevent uncontrolled cell growth. © 2016 Pearson Education, Inc.

Tumor-suppressor genes Tumor-suppressor gene Normal growthinhibiting protein Defective, nonfunctioning protein Cell division under control Cell division not under control (a) Normal cell growth © 2016 Pearson Education, Inc. Mutated tumor-suppressor gene (b) Uncontrolled cell growth (cancer) Figure 11. 17

The Progression of a Cancer • Nearly 150, 000 Americans will be stricken by cancer of the colon (the main part of the large intestine) this year. • Colon cancer, like many cancers, • is a gradual process and • is produced by more than one mutation.

Stepwise development of colon cancer Colon wall Cellular changes: DNA changes: © 2016 Pearson Education, Inc. 1 2 3 Increased cell division Growth of benign tumor Growth of malignant tumor Oncogene activated Tumor-suppressor gene inactivated Second tumor-suppressor gene inactivated Figure 11. 19

The Progression of a Cancer • The development of a malignant tumor is accompanied by a gradual accumulation of mutations that – convert proto-oncogenes to oncogenes and – knock out tumor-suppressor genes. Chromosomes Normal © 2016 cell Pearson Education, Inc. 1 mutation 2 mutations 3 mutations Figure 11. 20 4 mutations Malignant cell

Inherited Cancer • Multiple genetic changes are required to produce a cancer cell. • This helps explain the observation that cancers can run in families. • An individual inheriting an oncogene or a mutant version of a tumor-suppressor gene is one step closer to accumulating the necessary mutations for cancer. • Geneticists are therefore devoting much effort to identifying inherited cancer mutations so that predisposition to certain cancers can be detected early in life.

Inherited Cancer • About 15% of colorectal cancers involve inherited mutations. • There is also evidence that inheritance plays a role in 5– 10% of patients with breast cancer, a disease that strikes one out of every Breast cancer • Is usually not associated with inherited mutations • In some families can be caused by inherited, BRCA 1 cancer genes

Cancer Risk and Prevention • Cancer is the second leading cause of death (after heart disease) in most industrialized countries. • Most cancers arise from mutations that are caused by carcinogens, cancer-causing agents found in the environment, including • ultraviolet (UV) radiation and • tobacco products. © 2016 Pearson Education, Inc.

Table 11. 1 © 2016 Pearson Education, Inc.

Cancer Risk and Prevention • Some food choices significantly reduce a person’s cancer risk, including eating • 20– 30 g of plant fiber daily, • less animal fat, and • cabbage and its relatives, such as broccoli and cauliflower. • Determining how diet influences cancer has become an important focus of nutrition research.

Evolution Connection: The Evolution of Cancer in the Body • Medical researchers have been using an evolutionary perspective to gain insight into the development of tumors, such as the bone tumor shown in Figure 11. 22. • First, all evolving populations have the potential to produce more offspring than can be supported by the environment. Cancer cells, with their uncontrolled growth, clearly demonstrate such overproduction.

Figure 11. 22 © 2016 Pearson Education, Inc.

Evolution Connection: The Evolution of Cancer in the Body • Second, there must be variation among individuals of the population. • Third, variations in the population must affect survival and reproductive success. Indeed, the accumulation of mutations in cancer cells renders them less susceptible to normal mechanisms of reproductive control. • Mutations that enhance survival of malignant cancer cells are passed on to that cell’s descendants. In short, a tumor evolves.

Evolution Connection: The Evolution of Cancer in the Body • Viewing the progression of cancer through the lens of evolution helps explain why there is no easy “cure” for cancer but may also pave the way for novel therapies. • For example, some researchers are attempting to “prime” tumors for treatment by increasing the reproductive success of only those cells that will be susceptible to a chemotherapy drug. • Our understanding of cancer, like all other aspects of biology, benefits from an evolutionary perspective.

The Process of Science: Are Childhood Tumors Different? • Observations: Specific mutations can lead to cancer. • Question: Are different kinds of cancer associated with specific mutations? • Hypothesis: Young patients with medulloblastoma (MB) harbor unique mutations. (MB is the most common pediatric brain cancer and the deadliest form of childhood cancer. ) © 2016 Pearson Education, Inc.

The Process of Science: Are Childhood Tumors Different? • Prediction: The genetic map of MB cells from childhood tumors would have cancer-associated mutations not found in adult brain cancer tissue. • Experiment: Researchers sequenced all the genes in tumors from 22 pediatric MB patients and compared the genes with normal tissue from these same patients. © 2016 Pearson Education, Inc.

The Process of Science: Are Childhood Tumors Different? • Results: • Each tumor had an average of 11 mutations. • This is 5– 10 times fewer mutations than are found in adult MB patients. • Young MB patients therefore seem to have fewer, but deadlier, mutations. © 2016 Pearson Education, Inc.

Figure 11. 18 Tumor © 2016 Pearson Education, Inc.

Figure 11. UN 06 A typical operon Regulatory Promoter Operator gene Gene 1 DNA Produces repressor that in active form attaches to operator © 2016 Pearson Education, Inc. RNA polymerase binding site Gene 2 Gene 3 Switches operon Code for proteins on or off

Figure 11. UN 07 DNA unpacking Transcription RNA processing RNA transport m. RNA breakdown Translation Protein activation Protein breakdown © 2016 Pearson Education, Inc.

Figure 11. UN 08 Nucleus from donor cell © 2016 Pearson Education, Inc. Early embryo resulting from nuclear transplantation Embryo implanted in surrogate mother Clone of nucleus donor

Figure 11. UN 09 Nucleus from donor cell © 2016 Pearson Education, Inc. Early embryo resulting from nuclear transplantation Embryonic stem cells in culture Specialized cells

Figure 11. UN 10 Proto-oncogene (normal) Oncogene Mutation Normal protein Mutant protein Out-of-control growth (leading to cancer) Normal regulation of cell cycle Normal growth-inhibiting protein Defective protein Mutation Tumor-suppressor gene (normal) © 2016 Pearson Education, Inc. Mutated tumor-suppressor gene