Campbell Biology Chapter 18 Review: Regulation of Gene Expression

18.1 Operons: how bacteria switch genes on and off

pp. 351–356

On the AP exam? Yes

Topic 6.5 tests inducible versus repressible operons (lac and trp are the usual examples) and how a repressor and an operator work together. CAP and cAMP aren't named in the course, so treat the positive control of lac as background.

In the course: Topic 6.5 Regulation of Gene Expression, Topic 3.2 Environmental Impacts on Enzyme Function (notes, videos and more questions)

Key points

A bacterium can control a pathway in two ways. The fast way tweaks enzymes it already has, as when a pathway's end product slows its first enzyme (feedback inhibition). The slower, longer-lasting way changes how much of each enzyme gets made, usually by controlling transcription.
Bacteria often keep the genes for one job side by side behind a single promoter. The whole cluster is copied into one mRNA with several coding stretches, so one control point runs them all. The promoter, the operator and the genes together are called an operon.
The operator is a short DNA sequence that overlaps the promoter or sits just after it. When a repressor protein sits on it, RNA polymerase can't transcribe the genes. The repressor is made from its own gene, the regulatory gene, which usually lies elsewhere on the chromosome and turns out a small, steady supply of it.
Repressors are allosteric: a small molecule binding to one flips its shape. In a repressible operon such as trp, the repressor is made inactive, and the pathway's end product (the corepressor) switches it on. The genes shut down once there's plenty of product. Pathways that build things usually work this way.
In an inducible operon such as lac, the repressor is made active and keeps the genes off. An inducer (for lac, allolactose, made from lactose) pulls the repressor away, so the enzymes appear only when their food is around. Pathways that break nutrients down usually work this way.
Both kinds are negative control, because the active repressor turns genes off. Positive control uses an activator instead. For lac, the activator CAP works only with cAMP bound, and cAMP climbs when glucose runs low, so the lac genes are read strongly only when there's lactose around but little glucose.
Making only the enzymes a cell needs at the moment saves energy and raw materials, which is why natural selection has favored these control systems.

Key terms (14)

operon: A stretch of bacterial DNA with one promoter, one operator and a set of genes for related jobs, all transcribed into a single mRNA.
operator: A short DNA sequence at or next to the promoter where a repressor can bind. Whether it's occupied decides whether the operon is read.
repressor: A protein that turns genes off by binding the operator and keeping RNA polymerase from transcribing.
regulatory gene: A gene that makes the repressor for an operon. It often lies apart from the operon and runs at a slow, steady rate, so a few repressor molecules are always around.
corepressor: A small molecule, often the end product of a pathway, that binds a repressor and switches it on so it can block the operator.
inducer: A small molecule that binds a repressor and makes it release the operator, so the genes turn on.
repressible operon: An operon that's normally on and gets switched off when a small molecule builds up. Typical of pathways that build something.
inducible operon: An operon that's normally off and gets switched on when a small molecule appears. Typical of pathways that break down food.
negative control: Gene regulation in which the active regulatory protein, a repressor, turns transcription off.
positive control: Gene regulation in which a regulatory protein, an activator, binds DNA and turns transcription up.
activator: A protein that binds DNA near a gene and helps RNA polymerase start transcribing it.
catabolite activator protein (CAP): A bacterial activator that works only when cAMP is bound to it. It boosts the lac operon and others when glucose is scarce.
cyclic AMP (cAMP): A small signaling molecule made from ATP. In bacteria its level climbs when glucose runs low.
feedback inhibition: When the end product of a pathway slows an enzyme early in that pathway. It acts within seconds on enzymes that already exist.

Check yourself: 18.1 Operons: how bacteria switch genes on and off

4 questions on 18.1 Operons: how bacteria switch genes on and off. Pick an answer to see if you got it, and why.

Question 1 of 4

In a soil bacterium, three genes code for the enzymes that break down a plant sugar. When the sugar is added, the amounts of all three enzymes rise together within minutes. In a mutant missing one short DNA sequence just upstream of the first gene, none of the three enzymes is ever made. Which explanation best fits these results?

Question 2 of 4

A purified bacterial repressor protein is mixed with a short DNA fragment that contains its operator. The repressor binds the operator only when molecule M is also added. M is the final product of the pathway whose enzymes are coded by the operon. Which description fits this operon?

Question 3 of 4

In a hypothetical bacterial operon, RNA polymerase transcribes the genes well only while protein P is bound to a site next to the promoter. When small molecule X binds P, P changes shape and falls off the DNA, and transcription drops. Which statement correctly describes this system?

Question 4 of 4

A bacterium's operon for using sugar S is controlled by a repressor and also by an activator protein that works only when cAMP is bound to it. cAMP is high when glucose is scarce. Enzyme activity was measured in wild-type cells (invented data). Glucose | Sugar S | Enzyme activity (units) Absent | Absent | 2 Absent | Present | 900 Present | Present | 60 Present | Absent | 2 A mutant strain makes an activator that cannot bind cAMP; everything else is normal. If the mutant is grown with sugar S and no glucose, its enzyme activity would most likely be closest to which value?

0 of 4 answered

18.2 The many control points in eukaryotic cells

pp. 356–364

On the AP exam? Yes

Topics 6.5 and 6.6 cover chromatin marks (acetylation and methylation) as reversible epigenetic changes, transcription factors, promoters and enhancers, and the shared control of genes scattered across chromosomes; alternative splicing is in Topic 6.3. Mediator proteins, transcription factories and the ubiquitin–proteasome system are background.

In the course: Topic 6.5 Regulation of Gene Expression, Topic 6.6 Gene Expression and Cell Specialization, Topic 6.3 Transcription and RNA Processing (notes, videos and more questions)

Key points

Almost every cell in your body has the same genes. A nerve cell and a skin cell differ because each switches on its own set, and at any moment a cell uses only a small share of its genes.
Eukaryotes can adjust a gene's output at many steps: how tightly its DNA is packed, the start of transcription, RNA processing and export, how long the mRNA lasts, translation, and the activation and breakdown of the protein. The start of transcription is the most common control point.
Packing matters. Acetyl groups on histone tails cancel the tails' positive charge, loosening chromatin and making genes easier to transcribe, while removing them tightens it. Methyl groups on DNA cytosines usually keep genes quiet. These marks can be copied when cells divide and can also be removed, so they're reversible epigenetic changes that don't alter the DNA sequence.
RNA polymerase II and a set of general transcription factors gather at the promoter, but on their own they give only a trickle of RNA. Specific transcription factors (activators and repressors) set the real rate by binding control elements, some close to the promoter and some grouped into distant enhancers. The DNA loops so that activators on an enhancer can reach the promoter.
Control works by combinations. A small number of control-element types is mixed and matched, and a gene is transcribed strongly only in cells that contain the right set of activators. Genes scattered on different chromosomes can be switched on together if they share a control element, for example one recognized by a hormone bound to its receptor.
After transcription, alternative splicing lets one gene code for several proteins, and sequences in an mRNA's untranslated regions help set how long it lasts and whether ribosomes can start on it.
After translation, many proteins must be cut, chemically tagged (for example with phosphates) or shipped to the right place before they work. Cells also decide how long each protein lasts: ubiquitin tags mark a protein for a proteasome to chop up.

Key terms (15)

differential gene expression: Different cells using different sets of genes from the same genome. It's why a nerve cell and a skin cell look and work so differently.
chromatin: DNA together with the proteins, mainly histones, that package it in a eukaryotic nucleus.
heterochromatin: Chromatin that stays tightly packed; genes inside it are mostly kept off.
histone acetylation: Attaching acetyl groups to lysines in histone tails. It cancels their positive charge, loosens chromatin and makes nearby genes easier to transcribe.
DNA methylation: Adding methyl groups to DNA bases, usually cytosine. Heavily methylated genes are generally switched off.
epigenetic inheritance: Passing gene-expression patterns that don't depend on the DNA sequence, such as methylation marks, from a cell to its daughter cells. These marks can be reversed.
genomic imprinting: Silencing of one parent's copy of a gene by marks set in the egg or sperm, so only the other parent's copy is used.
control element: A short noncoding DNA sequence that a transcription factor binds in order to regulate a gene.
enhancer: A cluster of control elements that can sit thousands of bases from its gene, upstream, downstream or in an intron, and still boost that gene's transcription.
general transcription factors: Proteins every protein-coding gene needs for RNA polymerase to start at its promoter. On their own they give only a low rate.
specific transcription factor: An activator or repressor made only in certain cells or at certain times. It binds control elements to raise or lower a gene's transcription.
alternative RNA splicing: Joining different combinations of exons from the same pre-mRNA, so one gene can code for more than one protein.
untranslated region (UTR): The stretch at either end of an mRNA that isn't translated. Sequences here can control how long the mRNA lasts and whether ribosomes can start on it.
ubiquitin: A small protein that cells attach to other proteins as a 'destroy me' tag.
proteasome: A large barrel-shaped protein complex that unfolds ubiquitin-tagged proteins and chops them into short pieces.

Check yourself: 18.2 The many control points in eukaryotic cells

4 questions on 18.2 The many control points in eukaryotic cells. Pick an answer to see if you got it, and why.

Question 1 of 4

Lysines in histone tails carry a positive charge that helps the tails grip DNA's negatively charged backbone and pack nucleosomes tightly. Adding an acetyl group removes that charge. Researchers make yeast in which several tail lysines are replaced by another amino acid. In these yeast, genes near the altered histones fail to switch on when the cells are stressed, even though the right transcription factors are present. Which replacement was most likely made?

Question 2 of 4

Honeybee larvae with the same genes develop into queens if fed royal jelly throughout their growth and into workers otherwise. When researchers reduced the activity of a DNA methylation enzyme in young larvae, most developed into queen-like adults even without the special diet. Which conclusion do these results best support?

Question 3 of 4

An enhancer that drives a gene's expression in kidney cells normally sits 25,000 base pairs upstream of the promoter. Researchers move it to 25,000 base pairs downstream of the gene and also flip it end to end. Kidney cells still express the gene at a high level, and other cell types still don't. Which explanation fits best?

Question 4 of 4

0 of 4 answered

18.3 Noncoding RNAs that regulate genes

pp. 364–366

On the AP exam? Yes

Topic 6.6 says small RNAs help regulate gene expression, so know that miRNAs and siRNAs pair with mRNAs to block translation or trigger breakdown. Dicer, piRNAs and the details of RNA-guided chromatin silencing are background.

In the course: Topic 6.6 Gene Expression and Cell Specialization, Topic 6.5 Regulation of Gene Expression (notes, videos and more questions)

Key points

Only a tiny slice of the human genome, around 1–2%, codes for proteins, yet much more of it is transcribed. Many of those transcripts are noncoding RNAs (ncRNAs), and a lot of them help control other genes.
MicroRNAs (miRNAs) are about 22 nucleotides long. They come from RNA that folds back on itself into hairpins; an enzyme called Dicer trims each hairpin, and one strand of the short duplex is loaded into a protein complex.
The miRNA guides that complex to mRNAs with matching bases. A near-perfect match usually gets the mRNA cut; a partial match, the common case in animals, mainly blocks translation and speeds the mRNA's breakdown. Because only a short stretch has to match, one miRNA can quiet many different mRNAs.
Small interfering RNAs (siRNAs) are the same size and use the same machinery, but many are cut from one long double-stranded RNA, which can come from a virus or from the cell itself. Researchers use this RNA interference (RNAi) to switch off a chosen gene.
Some small RNAs work in the nucleus, steering proteins that pack chromatin into silent heterochromatin. In animals, piRNAs do this to transposons ('jumping genes') in the cells that make eggs and sperm.
Longer noncoding RNAs regulate genes too. For example, XIST RNA coats one X chromosome in female mammals and helps shut most of it down.
Extra layers of RNA-based control may have helped more complex body forms evolve. That idea is still being tested.

Key terms (10)

noncoding RNA (ncRNA): An RNA that does its job as RNA and is never translated into protein. Many help control other genes.
microRNA (miRNA): A single-stranded RNA about 22 nucleotides long, cut from a hairpin-shaped precursor, that guides a protein complex to matching mRNAs to block or destroy them.
small interfering RNA (siRNA): A short RNA like a miRNA, but cut from long double-stranded RNA, often many from one molecule. It silences mRNAs with a matching sequence.
RNA interference (RNAi): Silencing a gene with double-stranded RNA that matches it. Cells use it naturally, and scientists use it to switch genes off in experiments.
Dicer: The enzyme that trims double-stranded RNA into short pieces about 20–25 nucleotides long while miRNAs and siRNAs are being made.
hairpin: A stretch of RNA that folds back and pairs with itself, making a short double-stranded stem with a loop at one end.
piRNA: A class of small RNA in animals, made mostly in the cells that form eggs and sperm, that helps silence transposons.
transposon: A DNA segment that can move or copy itself to new spots in a genome, sometimes breaking a gene where it lands.
long noncoding RNA: A noncoding RNA longer than about 200 nucleotides. Some help pack chromatin, like XIST, which coats and silences one X chromosome in female mammals.
gene silencing: Shutting down a gene's output, either by blocking its transcription or by stopping its mRNA from being used.

Check yourself: 18.3 Noncoding RNAs that regulate genes

4 questions on 18.3 Noncoding RNAs that regulate genes. Pick an answer to see if you got it, and why.

Question 1 of 4

A mouse gene codes for a microRNA about 22 nucleotides long. Mice lacking this gene make far more of protein K, even though the gene for protein K is transcribed at the normal rate. How does the microRNA most likely keep protein K low in normal mice?

Question 2 of 4

When a plant virus copies its RNA genome, double-stranded viral RNA forms. Plant cells cut this RNA into many short pieces that guide the destruction of matching viral RNAs. Many plant viruses make a protein that binds tightly to these short RNA duplexes. What is the most likely effect of this viral protein?

Question 3 of 4

A biologist wants to test whether gene K is needed for flatworms to regrow a head after being cut in half. Flatworms take up double-stranded RNA from their food. Which experiment is best?

Question 4 of 4Calculator allowed

A microRNA usually recognizes its targets through a stretch of about 7 bases. Suppose the 3′ untranslated regions of all the different mRNAs in a cell add up to 25 million nucleotides, and assume the four bases occur at random. About how many places would match one particular 7-base sequence by chance?

0 of 4 answered

18.4 How one fertilized egg makes many cell types

pp. 366–373

On the AP exam? Yes

Topic 6.5 covers tissue-specific proteins and transcription factors switched on in sequence during development, and Topics 4.1 and 4.3 give morphogens and Hox genes as examples of signaling. You won't need maternal effect genes, the fruit fly experiments or any gene names.

In the course: Topic 6.5 Regulation of Gene Expression, Topic 6.6 Gene Expression and Cell Specialization, Topic 4.1 Cell Communication, Topic 4.3 Signal Transduction Pathways (notes, videos and more questions)

Key points

A zygote becomes an organism through three linked processes: cell division makes more cells, cell differentiation makes them specialized, and morphogenesis gives the body its shape. All three depend on which genes each cell expresses.
The first differences come from the egg. The mother's cells stock it with mRNAs and proteins (cytoplasmic determinants) that aren't spread evenly, so the first divisions hand different daughter cells different mixes, and those mixes switch on different genes.
Later, neighboring cells talk. Signals passed by contact or by secreted molecules change gene expression in the cells that receive them. This is induction, and it works through receptors and signal transduction pathways like those in Unit 4.
A cell is committed to its fate (determination) before it looks any different. Differentiation shows when tissue-specific proteins appear. Master regulatory genes often code for transcription factors that set off a chain of other genes, and some keep their own gene switched on, which locks the choice in.
Pattern formation puts each tissue in the right place. Positional information, often from morphogen gradients, tells a cell where it sits along the body's axes (head to tail, back to belly, left to right).
Maternal effect genes are the mother's genes whose products, placed in the egg, set up the early axes, so the offspring's early phenotype follows the mother's genotype. Later, homeotic genes (Hox genes in animals) tell each body region what to become, and mutations in them put body parts in the wrong place.
Much of this toolkit, including Hox genes, is shared by very different animals, which is strong evidence of common ancestry.

Key terms (13)

cell differentiation: The process by which a cell becomes specialized, making the proteins that give it its structure and job.
morphogenesis: The physical shaping of an organism and its parts, as cells change shape, move and organize into tissues.
cytoplasmic determinants: Maternal mRNAs and proteins placed unevenly in the egg. Cells that inherit different ones switch on different genes.
induction: When signals from nearby cells change a cell's gene expression and push it toward a particular fate.
determination: The point at which a cell becomes committed to its fate, before any outward sign of specialization appears.
tissue-specific protein: A protein made only in one kind of cell, like the insulin made by certain pancreas cells. Its appearance is the first clear sign that a cell has differentiated.
master regulatory gene: A gene whose protein, usually a transcription factor, can launch the whole program for one cell type by switching on many other genes.
pattern formation: Setting up the arrangement of tissues and organs so each one forms in the right place.
positional information: Molecular cues that tell a cell where it is along the body's axes and relative to its neighbors.
morphogen: A substance that forms a concentration gradient in an embryo. Cells respond differently to different concentrations, which sets their position-based fates.
maternal effect gene: A gene in the mother whose product, placed in the egg, shapes the offspring's early development, so the offspring's phenotype matches the mother's genotype.
homeotic gene: A master gene that decides what a body region becomes. When it's mutated, one body part can form where another belongs.
Hox genes: The homeotic genes of animals. They code for transcription factors switched on in order along the head-to-tail axis and are shared by very distantly related animals.

Check yourself: 18.4 How one fertilized egg makes many cell types

4 questions on 18.4 How one fertilized egg makes many cell types. Pick an answer to see if you got it, and why.

Question 1 of 4

In an amphibian embryo, a patch of cells that would normally become belly skin is moved into the brain-forming region of an early-stage host embryo. Patches taken from early-stage donors form brain tissue in their new spot. Patches taken from donors a day older form belly skin there, even though the hosts are the same age. At the time of the move, both kinds of patch look alike and make no skin-specific proteins. What best explains the difference?

Question 2 of 4

In the egg of a sea squirt, a patch of yellow cytoplasm ends up in the cells that later form tail muscle. Which observation would best show that this patch holds cytoplasmic determinants, rather than that muscle forms because of signals from neighboring cells?

Question 3 of 4

In an embryo, cells of group A release a signal protein that causes neighboring group B cells to become gland cells. Group B cells from a mutant have a receptor that binds the signal normally but can't start the relay pathway inside the cell. These mutant B cells are placed next to normal A cells. What is the most likely result?

Question 4 of 4

In a pond snail, shell coiling is set by a maternal effect gene: the right-coiling allele (D) is dominant to the left-coiling allele (d), and each snail's coiling depends on its mother's genotype, not its own. A dd female is crossed with a DD male. Which describes the coiling of the F₁ snails and of the offspring of an F₁ female?

0 of 4 answered

18.5 Cancer: when cell-cycle genes go wrong

pp. 373–377

On the AP exam? Yes

Topic 4.6 says broken cell-cycle control can lead to cancer, and Topic 6.7 covers the mutations behind it, so know proto-oncogenes versus tumor-suppressor genes and why several mutations are needed. The CED leaves out specific growth factors and cyclin–CDK pairs, so Ras, p53 and BRCA are background examples.

In the course: Topic 4.6 Regulation of Cell Cycle, Topic 6.7 Mutations, Topic 4.3 Signal Transduction Pathways (notes, videos and more questions)

Key points

Cancer starts when mutations in body (somatic) cells damage the genes that control the cell cycle. The mutations can come from chance copying errors, from carcinogens such as tobacco chemicals, UV light and X-rays, or from certain viruses.
Proto-oncogenes are normal genes whose products push the cell cycle forward, like growth factors, their receptors and relay proteins. A change that makes too much of the protein, or makes it overactive, turns a proto-oncogene into an oncogene. That can happen by moving the gene next to strong control elements, by copying it many times (amplification) or by a point mutation.
Tumor-suppressor genes code for proteins that hold division back, repair DNA, keep cells anchored or trigger apoptosis. Cancer can follow when their function is lost, which usually means both copies have to be knocked out.
Many of these genes code for parts of signaling pathways. A Ras protein stuck in the 'on' state sends a 'divide' message with no growth factor present. p53 is a transcription factor switched on by DNA damage; it turns on genes that pause the cycle, repair DNA or start apoptosis.
Usually several mutations have to pile up in one line of cells before it becomes cancerous (the multistep model), which is why cancer risk climbs with age.
Inheriting one mutant allele, such as a faulty BRCA1 or BRCA2 tumor-suppressor gene, gives a head start, so some cancers run in families. Even then, more mutations are needed in the body cells.
Some viruses promote cancer, for example by inserting their DNA near a proto-oncogene or by making proteins that disable tumor-suppressor proteins such as p53.

Key terms (12)

proto-oncogene: A normal gene whose product encourages cell division. Cells need it; it becomes dangerous only when a mutation makes it overactive.
oncogene: A gene that promotes cancer, usually a changed proto-oncogene that makes too much of a growth-promoting protein or a version that's always on.
tumor-suppressor gene: A gene whose product holds back cell division, repairs DNA or triggers cell death. Cancer can follow when both copies stop working.
gene amplification: The making of many extra copies of a gene in a cell, which can lead to far more of its protein.
translocation: A broken piece of one chromosome joining a different chromosome. It can put a gene under new control elements.
Ras: A small G protein that, while holding GTP, switches on a series of kinases after a growth factor binds its receptor. Mutant forms stuck 'on' drive many cancers.
p53: A transcription factor switched on by DNA damage. It turns on genes that pause the cell cycle, repair DNA or start apoptosis, which is why its loss is so common in cancer.
apoptosis: Programmed cell death: a controlled self-destruct that removes damaged or unneeded cells.
multistep model of cancer: The idea that a normal cell becomes cancerous only after several mutations add up in its line of descendants, which is why risk rises with age.
carcinogen: Anything that causes cancer, usually by damaging DNA, such as UV light, X-rays and chemicals in tobacco smoke.
somatic mutation: A mutation in a body cell rather than in an egg or sperm. It's passed to that cell's descendants but not to the person's children.
inherited predisposition: A higher cancer risk that comes from inheriting a mutant allele, such as a faulty tumor-suppressor gene, so fewer new mutations are needed.

Check yourself: 18.5 Cancer: when cell-cycle genes go wrong

4 questions on 18.5 Cancer: when cell-cycle genes go wrong. Pick an answer to see if you got it, and why.

Question 1 of 4

Cells from a certain tumor divide without limit and form tumors when injected into mice. When these tumor cells are fused with normal cells, the hybrid cells divide normally and don't form tumors. Which explanation fits best?

Question 2 of 4

Retinoblastoma is an eye tumor in young children. Some affected children inherited one mutant copy of the tumor-suppressor gene involved; others inherited two normal copies. Typical findings (invented data based on the real pattern): Group | Average age at diagnosis | Children with tumors in both eyes | Tumors per affected eye Inherited one mutant copy | 12 months | 70% | Often several No inherited mutation | 24 months | 0% | One Which explanation best accounts for these differences?

Question 3 of 4

In a growth pathway, growth factor F binds receptor R, R switches on relay protein G, G switches on kinase K1, K1 switches on kinase K2, and K2 activates a transcription factor that turns on genes for cell division. A new drug blocks K1. Tumors with each of the following mutations are treated with it. Which tumor's cells would most likely keep dividing despite the drug?

Question 4 of 4

Tumors from three patients are tested for a gene that codes for a growth-factor receptor (invented data). Normal cells have 2 copies of the gene. Sample | Gene copies per cell | Receptor protein (relative to normal) | Receptor's amino acid sequence Normal tissue | 2 | 1 | Normal Tumor 1 | 2 | 1 | One amino acid changed Tumor 2 | 18 | 10 | Normal Tumor 3 | 2 | 1 | Normal Which change most likely turned this proto-oncogene into an oncogene in tumor 2?

0 of 4 answered