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1 Indicate true (T) and false (F) statements below regarding gene control. Your answer
would be a four-letter string composed of letters T and F only, e.g. TTFT.
( ) Development of multicellular organisms from a fertilized egg only rarely involves DNA
rearrangements in specialized cells.
( ) A typical human cell expresses less than 1% of its approximately 30,000 genes at any
given time.
( ) Genes that are expressed in all cell types usually vary in their level of expression in
different cell types.
( ) Many differentiated plant cells can be fully de-differentiated and give rise to an entire
plant.
2 In the following schematic graph of a hypothetical set of RNA-seq data, the number of
reads is plotted for a region of chromosome containing two genes, from samples obtained from
two different tissues. Which gene (X or Y) do you think is more likely a “housekeeping” gene?
Which region (1 or 2) within gene Y most likely corresponds to an exon?
Number of reads
1 2
Liver
Brain
Gene X Gene Y
Position on chromosome
A. Gene X; region 1
B. Gene X; region 2
C. Both genes; region 1
D. Gene Y; region 1
E. Gene Y; region 2
3 Studying the expression of a transcription regulatory protein in two cell types, you have
performed experiments showing that the mRNA encoding the protein is present at comparable
levels in the cytosol of both cell types. However, based on the expression of its target genes, you
suspect that the protein activity might be significantly different in the two cell types. Which of the
following steps in expression of the gene encoding this protein is more likely to be differentially
controlled in these cell types?
A. Transcription
B. Translation
C. mRNA transport
D. mRNA degradation
5 What determines the time and place that a certain gene is transcribed in the cell?
A. The type of cis-regulatory sequences associated with it
B. The relative position of cis-regulatory sequences associated with it
C. The arrangement of various cis-regulatory sequences associated with it
D. The specific combination of transcription regulators present in the nucleus
E. All of the above
6 The majority of transcription regulators make sequence-specific contacts with DNA in the
major groove. In the two diagrams below, where are the contact surfaces that are exposed in the
major groove?
A. 1, 3
B. 1, 4
C. 2, 3
D. 2, 4
7 Considering the diagrams below that show hydrogen-bond donors and acceptors as well as
hydrophobic groups in four DNA base pairs, which of the following do you think is the most
difficult to accomplish by DNA-binding proteins?
9 Which of the following DNA-binding motifs uses β sheets to recognize DNA bases?
A. The helix–turn–helix motif
B. The leucine zipper
C. The zinc finger motif
D. The helix–loop–helix motif
E. None of the above
2 4 6 8 10 12 14 16
Position
13 Indicate true (T) and false (F) statements below regarding transcription regulators. Your
answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) About 10% of the protein-coding genes in most organisms encode transcription
regulators.
( ) The packaging of eukaryotic DNA into chromatin dampens the effect of cooperative
binding of transcription regulators.
( ) Some DNA-binding proteins can induce bends or kinks in their target DNA.
( ) Dimerization of transcription regulators increases the chance of binding to nonspecific
sequences.
14 The Trp operon in Escherichia coli encodes the components necessary for tryptophan
biosynthesis. In the presence of the amino acid in a bacterium, …
A. the tryptophan operator is bound to the tryptophan repressor.
B. the tryptophan repressor is bound to bacterial RNA polymerase.
C. the expression of the tryptophan repressor is shut off.
D. the operon genes are expressed.
E. All of the above.
15 Under which of the following conditions is the Lac operon in Escherichia coli fully turned
on?
A. Low glucose and lactose levels
B. Low glucose but high lactose levels
C. High glucose but low lactose levels
D. High glucose and lactose levels
E. Low cAMP and high glucose levels
A. the regulatory sequence encodes a regulatory protein that binds near the promoter of
the target gene and controls RNA polymerase binding.
B. the regulation of the target gene involves looping out of the intervening DNA, and the
promoter of the cis-regulatory sequence must be on the same chromosome.
C. the regulatory sequence can bind directly to the RNA polymerase.
D. the regulatory sequence cannot bind to a protein.
B
D
( ) Mediator
( ) cis-Regulatory sequence
( ) A general transcription factor
( ) “Spacer” DNA that may encode lncRNAs
Degree of methylation
A B
Transcribed region
Promoter
Genomic location
A B C D Heterochromatin
Bicoid
Hunchback
Giant
Krüppel
A B C D E
24 What would you expect to happen to the pattern of reporter expression in flies that lack
the gene encoding Giant?
A. It would be expressed in all seven stripes.
B. It would be expressed in stripe 5 only.
C. It would expand to cover a broad anterior region of the embryo.
D. It would fail to express efficiently in the stripe 2 region.
E. It would be expressed throughout the whole embryo.
25 What would you expect to happen to the pattern of reporter expression in flies that lack
the gene encoding Bicoid?
A. It would be expressed in all seven stripes.
B. It would be expressed in stripe 5 only.
C. It would expand to cover a broad anterior region of the embryo.
D. It would fail to express efficiently in the stripe 2 region.
26 In the Eve regulatory modules, the binding sites for Giant and Krüppel are usually close
to, or even overlapping with, those of Bicoid and Hunchback. This implies that Eve expression is
regulated by … between the activators and regulators.
A. Feedback regulation
B. Cooperation
C. Competition
D. Feed-forward regulation
27 In the following schematic drawings showing four different network motifs in gene
transcription circuits, indicate whether each of the motifs 1 to 4 corresponds to a feed-forward
loop (E), flip-flop device (F), negative feedback loop (N), or positive feedback loop (P). Your
answer would be a four-letter string composed of letters E, F, N, or P only, e.g. PNEF.
A A A A
B B B B
C C C C
1 2 3 4
A A
B B
C C
Coherent Incoherent
28 Considering the two particular feed-forward designs shown, would you expect the
coherent (C) or the incoherent (I) loop to have a stable output and respond best to input signals
that are above a certain threshold? Write down C or I as your answer.
29 Considering coherent and incoherent feed-forward loops, eight different designs are
possible using three components and involving activation (positive) and inhibition (negative)
regulation only. In all such loops, A would regulate both B and C, and B would regulate only C.
How many of these designs constitute a coherent loop? Write down your answer as a number, e.g.
7.
30 Would you expect a coherent (C) or an incoherent (I) loop to generate the following
response pattern? In this example, A is stimulated by the input, and the transcription of C is
measured as the output. Write down C or I as your answer.
Signal
Input
Output
0
Time
31 Indicate true (T) and false (F) statements below regarding DNA methylation in humans.
Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) Methylation of adenines is the most common DNA methylation in humans.
( ) Methylated cytosine can be accidentally deaminated to produce thymine, leading to a
C-to-T transition.
( ) Cytosine methylation often occurs within a 5′-CG-3′ sequence.
( ) Shortly after fertilization, a genome-wide wave of demethylation takes place.
32 Indicate true (T) and false (F) statements below regarding DNA methylation in humans.
Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) DNA methylation makes repression of gene expression “leakier.”
( ) DNA methylation at the promoter region is usually an indication of active
transcription.
( ) CG islands are nonpermissive for RNA polymerase assembly.
( ) The dinucleotide 5′-GC-3′ is much more common than 5′-CG-3′ in the human genome.
C B
35 In the following pedigree, females and males are indicated by circles and squares,
respectively, and the presence of a rare disease caused by a loss-of-function mutation in an
imprinted autosomal gene is indicated by black color. Is the gene maternally imprinted (M; i.e. not
expressed from the maternally inherited chromosome) or paternally imprinted (P)? Write down M
or P as your answer.
37 You have engineered the X chromosomes in female mice such that one X chromosome
expresses green fluorescent protein when active, while the other expresses red fluorescent protein.
You have used these mice to study cancer in females. You know that each tumor is a clonal
cellular proliferation, meaning all of its proliferating cells are descendants of a single original
cancer-causing cell. It follows that, unless X-chromosome inactivation is perturbed in tumors, …
A. all tumor cells in one mouse should express the same fluorescent protein (either red or
green), but tumor cells from different mice can show either red or green fluorescence.
B. the cells in any tumor should all express the same fluorescent protein (either red or
green), but independently derived tumors in the same mouse can show either green or
red fluorescence.
C. different cells within each tumor can express different fluorescent proteins, and the
tumors would therefore show yellow fluorescence, but each cell shows either red or
green fluorescence.
D. each cell can express both fluorescent proteins and would therefore emit yellow
fluorescence, and the tumors would glow in yellow as well.
39 Two copies of the gene A exist in a diploid mammal. However, only one copy is expressed
in every somatic cell. Different somatic cells in the body of each organism have inactivated one or
the other allele in a seemingly random fashion, but when they divide, the daughter cells inherit the
choice of the inactive allele faithfully. This is an example of …
A. X-inactivation
B. Genomic imprinting
C. Loss of heterozygosity
D. Monoallelic gene expression
E. Alternative gene splicing
40 Indicate true (T) and false (F) statements below regarding riboswitches. Your answer
would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) A riboswitch permits transcription elongation only when bound to its small-molecule
ligand.
( ) Riboswitches appear to be a modern evolutionary invention.
( ) Riboswitches are often located near the 3′ end of mRNAs, and therefore fold after the
rest of the mRNA.
( ) Riboswitches are exclusively found in prokaryotes.
41 In the following schematic diagram of five pairs of alternative RNA splicing patterns,
which pair depicts exon skipping only? In exon skipping, an exon is spliced out of the RNA
transcript along with its flanking introns. In the diagram, exons are colored dark blue and introns
are colored yellow. Light blue indicates possible exons.
42 Imagine a gene encoding a pre-mRNA with twelve exons, ten of which can be alternatively
spliced in vivo. Assuming that alternative splicing for this RNA only occurs through exon
skipping, how many different proteins can possibly be made from this pre-mRNA as a result of
alternative splicing?
A. About 10
B. About 20
C. About 100
D. About 200
E. About 1000
43 The alternative splicing of a certain transcript can result in the production of two mRNA
isoforms, one predominant in muscle cells and the other in neurons. The gene contains an exon
that is skipped in muscle cells but retained in neurons. You create a mutant version of the gene in
which the 3′ splice site near this exon is deleted. However, when you introduce this into a culture
of neural cells, an even longer pre-mRNA is produced, consistent with the activation of a
secondary splice site located near the deleted one. Is the secondary splice site within the exon (E)
or its neighboring intron (I)? Write down E or I as your answer.
45 Indicate true (T) and false (F) statements below regarding RNA editing. Your answer
would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) RNA editing in animal cells mainly takes place through adenine or cytosine
deamination.
( ) RNA editing can change the pattern of pre-mRNA splicing.
( ) RNA editing in coding regions can result in changes in the protein sequence.
( ) Retroviruses such as HIV encode RNA-editing components to confront the host
defense mechanisms.
46 You have transfected HeLa cells with a gene encoding the human immunodeficiency virus
(HIV) protein Rev and have induced the expression of the protein. You incubate the cell culture in
the presence or absence of leptomycin B and later measure the localization of Rev inside the cells
by immunofluorescence microscopy. Leptomycin B specifically inhibits the cellular Crm1 protein,
a nuclear transport receptor that is essential for the normal function of Rev in the HIV life cycle.
Your results are tabulated below. Which condition (1 or 2) do you think corresponds to the
presence of leptomycin B?
2 3 97
47 When unfolded proteins accumulate in the lumen of the endoplasmic reticulum due to
inefficient folding conditions, a membrane-bound protein kinase is activated and phosphorylates a
subunit of the translation initiation factor eIF2. Indicate which of the following events would (Y)
or would not (N) occur as a result. Your answer would be a four-letter string composed of letters
Y and N only, e.g. YYYY.
( ) eIF2 binds tightly to the ribosome.
( ) Translation initiation is stimulated.
( ) The GDP-bound form of eIF2 accumulates.
( ) eIF2B is activated.
48 A researcher studying the human immunodeficiency virus (HIV) has infected human T
cells with wild-type or Rev-deficient viruses. She extracts cytoplasmic RNA from the cells and
separates each isolated RNA mixture by agarose-gel electrophoresis. She then uses northern
analysis using HIV-specific probes to identify those bands that contain viral RNA. The results are
presented in the following schematic drawing. Which lane (1 or 2) corresponds to cells infected
with the Rev-deficient virus? What is the size of the full-length HIV genome?
1 2
Apparent length
(×1000 nt)
49 Some viruses encode a protease that cleaves the translation initiation factor eIF4G,
rendering it unable to bind to eIF4E. What is the consequence of this cleavage?
A. It shuts down most of the cellular translation machinery, which causes the release of
virus particles.
B. It favors viral protein synthesis because IRES-dependent translation initiation is
inhibited.
C. It shuts down most host-cell protein synthesis and diverts the translation machinery to
IRES-dependent initiation, thus favoring viral protein synthesis.
D. It favors viral protein synthesis by shutting down translation from uORFs.
E. It shuts down IRES-dependent translation, forcing the virus into latency.
50 Gcn4 is a protein kinase that can phosphorylate and inactivate the initiation factor eIF2.
The Gcn4 mRNA contains several short upstream open reading frames (uORFs) that negatively
regulate its translation initiation. The phosphorylation of eIF2 by Gcn4, therefore, can control
Gcn4 expression …
A. in a negative feedback loop.
B. in a positive feedback loop.
C. in a feed-forward loop.
51 Indicate true (T) and false (F) statements below regarding mRNA stability and
degradation. Your answer would be a four-letter string composed of letters T and F only, e.g.
TTFT.
( ) Any factor that affects the translation efficiency of an mRNA tends to have the
opposite effect on its degradation.
( ) Decapping of mRNA normally occurs after poly-A tail shortening removes the poly-A
tail and starts chewing into the 3′-UTR.
( ) Most mRNA decay in the cells generally proceeds via endonucleolytic cleavage.
( ) As a general rule, eukaryotic mRNAs have a shorter half-life compared to bacterial
mRNAs.
53 Indicate true (T) and false (F) statements below regarding P-bodies. Your answer would
be a four-letter string composed of letters T and F only, e.g. TTFT.
( ) P-bodies are membrane-enclosed organelles scattered throughout the cytoplasm.
( ) mRNAs that are to be degraded are transferred from P-bodies to stress granules
containing decapping and exonuclease enzymes.
( ) When translation initiation is blocked, stress granules typically shrink.
( ) mRNAs associated with stress granules are primed for translation.
54 Which of the following classes of noncoding RNAs is NOT directly involved in RNA
interference?
A. miRNA
B. snoRNA
C. piRNA
D. siRNA
55 Indicate whether each of the following descriptions better matches miRNAs (M) or
siRNAs (S) in animal cells. Your answer would be a four-letter string composed of letters M and
S only, e.g. MMMM.
( ) They usually cleave their target RNAs using the slicing activity of the Argonautes.
( ) They typically show perfect complementarity with their target RNA.
( ) They can bind to the RITS as well as the RISC complex.
( ) They seem to be the more ancient form of small noncoding RNAs.
56 Which strand in an miRNA precursor will serve as the guide strand in the RNA-induced
silencing complex (RISC)? Analysis of miRNA sequences has revealed an asymmetry in the
stability of the double-stranded RNA precursor. The strand showing lower thermodynamic
stability near its 5′ end (nucleotides 2 to 6 in the mature guide strand) is normally selected as the
guide strand, and the other strand is usually degraded. In the following miRNA precursor, which
strand (1 or 2) do you think will be incorporated into the active RISC? Write down 1 or 2 as your
answer.
1 5′ CAAAGUGCUUACAGCGCAGGUAG 3′
2 3′ GAUGUUCACGGAAGUGGCGUC-A 5′
57 The schematic diagram below shows the processing of a class of small RNAs that are
involved in RNA interference (RNAi). Which of the following is true regarding these RNAs?
59 A certain region of a mammalian genome is transcribed at low but sustained levels using
two flanking promoters. The RNA products are annealed together, processed, and used to recruit
the RITS complex to this region, as well as chromatin modifying enzymes, RNA-dependent RNA
polymerase, and a Dicer enzyme. Indicate whether this pathway is more closely related to that
seen in miRNA (M), piRNA (P), or siRNA (S) interference pathways. Write down M, P, or S as
your answer.
60 In many animals, siRNAs can only function within the cell in which the siRNA is
introduced. In contrast, the worm Caenorhabditis elegans can be fed with bacteria that synthesize
double-stranded RNAs, and the RNAi spreads throughout the animal. A genetic screen to identify
genes involved in systemic RNAi led to the discovery of Sid-1, a transmembrane protein
expressed in most tissues in the adult worm. Loss-of-function mutations in the gene encoding Sid-
1 restrict the RNAi activity to the cells surrounding the digestive tract after siRNA feeding.
Ectopic expression of Sid-1 in Drosophila melanogaster cells that normally lack systemic RNAi
and are unable to take up siRNAs from the medium, enables these cells to passively take up
siRNA . These findings suggest that …
A. Sid-1 is necessary and sufficient for systemic RNAi and siRNA uptake, respectively.
B. Sid-1 is necessary but not sufficient for systemic RNAi and siRNA uptake,
respectively.
C. Sid-1 is not necessary but is sufficient for systemic RNAi and siRNA uptake,
respectively.
D. Sid-1 is not necessary and not sufficient for systemic RNAi and siRNA uptake,
respectively.
61 Comparing the bacterial CRISPR system and the eukaryotic RNAi mediated by siRNAs,
indicate whether each of the following CRISPR components is most analogous to Argonaute (A),
siRNA (S), or target mRNA (T) in the RNAi pathway. Your answer would be a three-letter string
composed of letter A, S, and T only.
( ) Cas
( ) Viral DNA
( ) crRNA
62 Consider the descriptions below for three different lncRNAs, and determine whether they
function in cis (C) or in trans (T). Your answer would be a three-letter string composed of letters
C and T only, e.g. CCT.
( ) The tsiX RNA is transcribed from the X-inactivation center in the X chromosome that
will not be inactivated. It is antisense with respect to Xist, repressing its transcription
and function.
( ) The ANRIL lncRNA is an antisense transcript in a gene cluster expressing inhibitors of
cell-cycle proteins. It silences the entire cluster by recruiting heterochromatin proteins
of the Polycomb group.
( ) The PTENP1 lncRNA is similar to an mRNA that encodes the protein PTEN, and
contains many of the miRNA response elements present in PTEN mRNA; it therefore
protects the PTEN mRNA from miRNA-mediated silencing by acting as a decoy.
Answers:
1. Answer: TFTT
Difficulty: 1
Section: An Overview of Gene Control
Feedback: The changes in gene expression that underlie the development of multicellular
organisms do not generally involve changes in the DNA sequence of the genome. At any
one time, a typical human cell expresses 30–60% of its approximately 30,000 genes at
some level. But even those genes that are expressed in all cell types usually vary in their
level of expression from one cell type to the next. Under the right conditions,
differentiated plant cells can regenerate an entire adult plant.
2. Answer: D
Difficulty: 3
Section: An Overview of Gene Control
Feedback: A housekeeping gene is expected to be expressed in nearly all cells, including
brain and liver cells. This is the case for gene Y, for which the mRNA levels are significant
in both cell types, according to the RNA-seq data. The regions with higher numbers of
reads in the RNA-seq results correspond to exons.
3. Answer: B
Difficulty: 2
Section: An Overview of Gene Control
Feedback: Since the mRNA levels are similar in both cell types, difference in protein
activity can be attributed to differences in translation or in post-translational control.
4. Answer: A
Difficulty: 2
Section: An Overview of Gene Control
Feedback: Ubiquitously expressed gene products include ribosomal proteins, DNA and
RNA polymerases, and DNA repair enzymes, among others.
5. Answer: E
Difficulty: 2
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: The expression of a gene can be determined by its cis-regulatory sequences and
transcription regulators that function in trans.
6. Answer: B
Difficulty: 2
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: Nearly all transcription regulators make the majority of their contacts with the
major groove (1 and 4 in the drawings) because the major groove is wider and displays
more molecular features than does the minor groove (2 and 3).
7. Answer: D
Difficulty: 2
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: In the minor groove, precise recognition of A-T versus T-A (or C-G versus G-
C) is not readily feasible. However, an A-T can still be distinguished from C-G, for
example.
8. Answer: B
Difficulty: 1
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: DNA-binding proteins typically recognize specific sequences that are 5 to 10
nucleotide pairs in length. This involves forming 20 or so weak interactions at the
interface, including hydrogen-bonding, ionic bonding, and hydrophobic interactions. The
sum of all protein–DNA interactions can result in high affinity and specificity.
9. Answer: E
Difficulty: 1
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: All of the examples presented in A to D use α helices to interact with DNA. A
limited number of DNA-binding motifs use β sheets to recognize DNA bases.
10. Answer: T
Difficulty: 3
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: Homodimeric transcription regulators typically have a symmetrical arrangement
which is reflected in their target DNA sequence in the form of an inverted repeat. The
sequence logo shown is not in agreement with an inverted repeat, or even a direct repeat;
the DNA is therefore expected to be recognized by a heterodimer.
11. Answer: E
Difficulty: 3
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: The expected number of target 8-mer sequences is calculated as:
(6 × 109 8-mer/genome) × (2 orientations per double strand) / (48 8-mers/target sequence)
= ~200,000 target sequences/genome.
Similarly, the expected number of target 16-mer sequences is calculated as:
(6 × 109 16-mer/genome) × (2 orientations per double strand) / (416 16-mers/target
sequence)
= ~3 target sequences/genome.
12. Answer: D
Difficulty: 1
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: Cooperative binding creates a sigmoidal binding curve with two main states: at
low protein concentrations, the protein is mostly a monomer and the binding site on DNA
is mostly unoccupied; at high protein concentrations, the great majority of the DNA sites
are occupied by the protein dimer.
13. Answer: TFTF
Difficulty: 1
Section: Control of Transcription by Sequence-specific DNA-binding Proteins
Feedback: Nucleosome packaging of DNA and dimerization of transcription regulators
promote cooperative DNA binding by these proteins. Some proteins that bind to DNA can
significantly bend the DNA molecule. About 10% of protein-coding genes in most cells
encode transcription regulators, making them one of the largest classes of proteins in the
cell.
14. Answer: A
Difficulty: 1
Section: Transcription Regulators Switch Genes On and Off
Feedback: When tryptophan is present, it binds to the repressor which then binds to the
operator to turn off the operon.
15. Answer: B
Difficulty: 1
Section: Transcription Regulators Switch Genes On and Off
Feedback: The Lac operon is fully turned on when glucose is absent AND lactose is
present.
16. Answer: B
Difficulty: 2
Section: Transcription Regulators Switch Genes On and Off
Feedback: DNA looping can occur during bacterial gene regulation, where the intervening
DNA acts as a tether to enormously increase the probability that the proteins bound near
the promoter and those bound to the cis-regulatory sequences will collide with each other.
This effect requires that both sequences be on the same DNA molecule, or be somehow
linked physically.
17. Answer: B
Difficulty: 2
Section: Transcription Regulators Switch Genes On and Off
Feedback: Variation in transcription rates across the genome is much greater in eukaryotic
cells (about one million-fold) compared to prokaryotic cells (about one thousand-fold). In
eukaryotes, genes are often transcribed and regulated individually, and DNA looping
occurs in the regulation of nearly every gene. In these cells, transcription regulators often
assemble in groups and do not directly contact RNA polymerases. The default state of
most eukaryotic DNA packaged into nucleosomes is off.
18. Answer: E
Difficulty: 1
Section: Transcription Regulators Switch Genes On and Off
Feedback: Eukaryotic transcription activator proteins can direct local alterations in
chromatin structure. This can be achieved through covalent histone modifications,
nucleosome remodeling or removal, and histone replacement.
19. Answer: DBAC
Difficulty: 2
Section: Transcription Regulators Switch Genes On and Off
Feedback: Please refer to Figure 7–17.
20. Answer: B
Difficulty: 3
Section: Transcription Regulators Switch Genes On and Off
Feedback: The methylation mark would be found in the body of actively transcribed genes
(but not near their promoter, which requires a more open nucleosome packaging).
21. Answer: D
Difficulty: 2
Section: Transcription Regulators Switch Genes On and Off
Feedback: The combined effect of two transcription activators binding to the same
regulatory sequence in DNA is synergistic, not simply additive.
22. Answer: C
Difficulty: 3
Section: Transcription Regulators Switch Genes On and Off
Feedback: Gene D is not protected from heterochromatin expansion by any barrier
sequence, while genes A and B are repressed by the cis-regulatory element bound to a
repressor. Gene C, however, is not under these repressive effects, thanks to its flanking
insulator elements and barrier sequences.
23. Answer: B
Difficulty: 1
Refer to: Even-skipped Regulatory Module
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: This module is normally activated in the second stripe, where inhibition is weak
and activation is strong.
24. Answer: C
Difficulty: 2
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: As expected, lack of Giant or Krüppel results in a broad expression pattern for
the second stripe.
25. Answer: D
Difficulty: 2
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: As expected, lack of Bicoid or Hunchback results in an inefficient expression of
the second stripe.
26. Answer: C
Difficulty: 2
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: This helps sharpen the boundaries flanking the Eve stripes.
27. Answer: PENF
Difficulty: 2
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: The circuits 1 and 3 include indirect feedback loops (with positive and negative
feedback, respectively). Circuit 4 has two interconnected flip-flop switches.
28. Answer: C
Difficulty: 3
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: This also depends on the particular parameters of the system. However,
coherent feed-forward motifs are generally more stable and more robust to perturbations.
29. Answer: 4
Difficulty: 2
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: Half of the possible designs yield coherent loops.
30. Answer: I
Difficulty: 3
Section: Molecular Genetic Mechanisms that Create and Maintain Specialized Cell Types
Feedback: The two-phase response reflects the incoherent nature of this feed-forward
motif.
31. Answer: FTTT
Difficulty: 1
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: The most common DNA methylation in vertebrate DNA occurs on cytosine (C)
nucleotides largely in the sequence 5′-CG-3′. The accidental deamination of the methylated
cytosine can then potentially lead to a mutation. Shortly after fertilization in mammals, a
genome-wide wave of cytosine demethylation takes place and the vast majority of methyl
groups are lost from the DNA.
32. Answer: FFFT
Difficulty: 2
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: DNA methylation helps to make repression of gene expression less leaky. RNA
polymerase is often found bound to promoters within unmethylated CG islands, even when
the associated gene is not being actively transcribed. Except in CG islands, 5′-CG-3′
dinucleotides are rare in vertebrate genomes.
33. Answer: CAB
Difficulty: 2
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: Arrow A represents the maintenance of DNA methylation after DNA
replication, while arrows B and C represent de novo DNA methylation and DNA
demethylation, respectively.
34. Answer: P
Difficulty: 3
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: On the maternally inherited chromosome, H19 is transcribed and silences Igf2.
This does not occur on the paternal chromosome. As a result, Igf2 is maternally imprinted
with no maternal-specific methylation.
35. Answer: M
Difficulty: 3
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: If a disease-causing gene is maternally imprinted, carrier females silently pass it
to the next generation; their sons may have affected children, but their daughters would
not.
36. Answer: A
Difficulty: 2
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: Genomic imprinting, observed in placental mammals and some flowering plants,
is an epigenetic form of inheritance. It is mediated through DNA methylation in mammals,
but it does not always involve gene inactivation by direct methylation. It can unmask
recessive alleles or mask dominant alleles.
37. Answer: B
Difficulty: 2
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: Since different cells in the female body have randomly inactivated one or the
other X chromosome, tumors derived from them will inherit the inactivation pattern and
can therefore express one or the other fluorescent protein. However, all cells within each
tumor are expected to express the same fluorescent protein.
38. Answer: dosage compensation
Difficulty: 2
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: Dosage compensation allows mammals to equalize the dosage of X-
chromosome gene products between males and females.
39. Answer: D
Difficulty: 1
Section: Mechanisms that Reinforce Cell Memory in Plants and Animals
Feedback: Monoallelic expression can result from genomic imprinting, but not all
examples of monoallelic expression are due to imprinting.
40. Answer: FFFF
Difficulty: 2
Section: Post-transcriptional Controls
Feedback: Riboswitches are short RNA sequences that can change conformation upon
ligand binding and regulate transcription. These ancient regulators are common in bacteria
as well as in eukaryotes. They are often found near the 5′ end of mRNAs and fold co-
transcriptionally.
41. Answer: A
Difficulty: 2
Section: Post-transcriptional Controls
Feedback: The alternative splicing event shown in A is exon skipping: the third exon is
missing (together with its flanking introns) in one of the two mRNA variants. Shown in B
is the retention of a single intron (together with its flanking exons) in one of the mRNA
variants.
42. Answer: E
Difficulty: 2
Section: Post-transcriptional Controls
Feedback: Each alternative exon is either skipped or retained, possibly creating 210 (=
~1000) different mature mRNAs.
43. Answer: I
Difficulty: 2
Section: Post-transcriptional Controls
Feedback: The cryptic splice site resides within the upstream intron, resulting in the
production of a longer mRNA when this splice site is chosen.
44. Answer: B
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: The suboptimal cleavage/poly-A addition site in the transcript is encountered
first but is usually skipped in unstimulated B lymphocytes, leading to production of a
longer antibody molecule that is anchored in the plasma membrane. When activated to
produce antibodies, the B lymphocyte increases its CstF concentration; as a result,
cleavage now occurs at the suboptimal site, and the shorter transcript is produced.
45. Answer: TTTF
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Two principal types of mRNA editing in animals are the deamination of adenine
to produce inosine and, less frequently, the deamination of cytosine to produce uracil.
Both types can have profound effects on the meaning of the RNA message, including
changing the pattern of pre-mRNA splicing or changing the amino acid sequence of the
protein coded by the mRNA. RNA from some retroviruses, including the human
immunodeficiency virus (HIV), is extensively edited by the host cell, presumably as part of
a defense mechanism to hold the virus in check.
46. Answer: 2
Difficulty: 2
Section: Post-transcriptional Controls
Feedback: By inhibiting Crm1, leptomycin B inhibits the nuclear export of Rev, resulting in
its nuclear accumulation.
47. Answer: NNYN
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Under stress conditions, eIF2 phosphorylation prevents its release from the
guanine nucleotide exchange factor eIF2B, sequestering the latter in a nonfunctional form,
and consequently preventing further eIF2 guanine nucleotide exchange and activation. As
a result, translation initiation is largely inhibited.
48. Answer: D
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: In the absence of a functional Rev protein (lane 2), only the fully spliced viral
RNAs are exported from the nucleus to the cytosol. Rev is required for the export of the
full-length viral RNA.
49. Answer: C
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Translation of internal ribosome entry site (IRES)-containing mRNAs does not
rely on the common cap-dependent initiation mechanism.
50. Answer: B
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Since phosphorylated eIF2 promotes the skipping of the uORFs in favor of the
translation of the main Gcn4 ORF, the kinase activity of Gcn4 provides a possible positive
feedback control mechanism.
51. Answer: TFFF
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Eukaryotic mRNAs are generally more stable than bacterial mRNA. Eukaryotic
mRNA decay is mediated by 5′ exonucleases (after decapping) or 3′ exonucleases, usually
after poly-A tail shortening leaves only about 25 nucleotides of the tail. Since the poly-A
shortening and the translation machinery compete for the same components, factors that
affect one of them also affect the other one in an opposite direction. Some mRNAs are
destroyed by specific endonucleases.
52. Answer: A
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: The iron-sensitive RNA-binding protein aconitase can bind to the 3′
untranslated region (UTR) of the transferrin receptor mRNA and increase production of
the receptor by blocking endonucleolytic cleavage of the mRNA. The addition of iron to
cells results in the release of aconitase from the mRNA and thus decreases the stability of
the mRNA.
53. Answer: FFFT
Difficulty: 1
Section: Post-transcriptional Controls
Feedback: Even though they somehow function as “organelles,” P-bodies are not
membrane-enclosed. Many mRNAs are degraded in P-bodies, but some mRNAs move
from P-bodies to stress granules, which contain mRNA-binding proteins that prime the
mRNAs for translation. Translation itself, however, does not occur in stress granules.
When translation initiation is blocked, stress granules enlarge as more and more
nontranslated mRNAs are stored in them.
54. Answer: B
Difficulty: 1
Section: Regulation of Gene Expression by Noncoding RNAs
Feedback: The small nucleolar RNAs do not function in RNA interference.
55. Answer: SSSS
Difficulty: 2
Section: Regulation of Gene Expression by Noncoding RNAs
Feedback: The small interfering RNAs (siRNAs) appear to be the most ancient form of
RNA interference. Having an exact match to their target RNA molecules, they direct the
cleavage of the target. siRNAs can also control transcription of target genes by binding to
the RNA-induced transcriptional silencing (RITS) complex.
56. Answer: 1
Difficulty: 2
Section: Regulation of Gene Expression by Noncoding RNAs
Feedback: Note the presence of mismatches and even a bulge along the duplex. Strand 1
contains mostly A-U base pairs, as well as a mismatch, near its 5′ end (left). Strand 2
contains mostly C-G pairs near its 5′ end (right).
57. Answer: C
Difficulty: 2
Section: Regulation of Gene Expression by Noncoding RNAs
Feedback: These are miRNAs
58. Answer: C
Difficulty: 1
Section: Regulation of Gene Expression by Noncoding RNAs
Feedback: The RNA interference (RNAi) response can be amplified in some organisms
using RNA-dependent RNA polymerases. In these cases, RNA-dependent RNA