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Chapter 10 Gene Action: From DNA to Protein

READINGS

Chapter Opener
An Inborn Error of Arginine Production

CHAPTER OVERVIEW

Information flow is at the root of all genetics. This chapter discusses the
transcription of genetic information to messenger RNA molecules and
then the utilization of that information as several types of RNA and
protein molecules assemble, transiently, in the cytoplasm to translate
the information into the amino acid sequence of a protein. The final
protein is the result of processing. Most of the genome’s information
does not lead to protein production, and those genes that are
transcribed and translated do so as part of an unfolding program of
development or in response to certain signals, discussed in depth in the
next chapter. All organisms use the same genetic code to transcribe
DNA to RNA and to translate RNA to protein. The universality of the
genetic code is an important part of the abundant evidence that life on
earth evolved from a common ancestor.

CHAPTER OUTLINE

10.1 Transcription Copies the Information in DNA

1. The coding portion of our genome is termed the exome.

2. The exome constitutes approximately 1.5 percent of our genome and encodes about
20,325 proteins. Most of the rest of the genome controls gene expression.
3. Transcription copies the information from DNA; translation uses the RNA’s
information to construct amino acid chains that comprise proteins.
4. Transcription copies the information from one strand of the DNA double helix, called
the template strand, into RNA.
5. Proteins must fold into their functional 3 dimensional shapes.

RNA Structure and Types

1. The DNA strand from which RNA is copied is the template strand, and the other
strand of DNA is the coding strand.
2. RNA polymerase catalyzes the synthesis of RNA.
3. RNA differs from DNA in that it is generally single-stranded, has uracil instead of
thymine, and has the sugar ribose instead of deoxyribose.
4. These differences enable RNA to fold into 3 dimensional conformations.
5. There are three main classes of RNA.
6. Messenger RNA (mRNA) carries the information that specifies a particular amino
acid sequence. Each three mRNA bases in a row form a codon.
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
7. Ribosomal RNA (rRNA) joins with certain proteins to form ribosomes.
8. Ribosomes physically support the other structures involved in protein synthesis, and
some rRNA catalyzes formation of peptide bonds.
9. Transfer RNA (tRNA) folds into a cloverleaf-shape. It carries a specific amino acid at
one end. One of its loops forms an anticodon, which is complementary to a specific
mRNA codon.

Transcription Factors

1. Transcription factors are proteins that control which genes are transcribed in a cell
under certain conditions by binding DNA in response to signals from outside the cell.
2. Transcription factors bind DNA at specific binding domains, forming a pocket that
allows RNA polymerase to start building an mRNA molecule.
3. Defects in transcriptional factors can cause disease.

Steps of Transcription

1. In transcription initiation, transcription factors bind promoter sequences in a gene.

This attracts RNA polymerase.
2. In transcription elongation, enzymes unwind the DNA, and RNA polymerase inserts
complementary free RNA bases opposite the template strand of the DNA double
helix, synthesizing RNA in a 5’ to 3’ direction.
3. A specific sequence in the DNA terminates transcription.

RNA Processing

1. mRNA is modified before it enters the cytoplasm. It gains a modified nucleotide cap
and a poly A tail.
2. Introns are sequences that are transcribed but then cut themselves out before exiting
the nucleus. The protein-encoding exons of the mRNA join and are proofread.
3. Alternate splicing cuts mRNA in different ways, forming slightly different
combinations of exons for some genes.
4. The mRNA must be exported from the nucleus before it is translated.

10.2 Translation of a Protein

The Genetic Code

1. The genetic code is the correspondence between mRNA codons and the 20 amino
acids of life.
2. Crick and coworkers confirmed the triplet nature of the genetic code.
3. The reading frame of a gene is the amino acid sequence that is encoded from a
certain point in a gene. Adding or subtracting 1 or 2 DNA bases to a gene disrupts
the reading frame. Adding or deleting 3 contiguous bases adds or deletes one amino
acid to the protein product but does not disrupt the reading frame.
4. The genetic code is nonoverlapping, but a gene can be read in three reading frames.
An open reading frame is a sequence of DNA that does not include a “stop” codon.
5. The genetic code is universal, with exceptions in mitochondria and a few single-
celled organisms.
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
6. Experiments that translated synthetic RNA molecules revealed the 61 codons that
specify amino acids. The other 3 codons signify “stop” and one signifies methionine
and “start.”
7. The genetic code is degenerate in that some amino acids are specified by more than
one codon (termed synonymous). Codons that specify different amino acids are
termed non-synonymous.

Building a Protein

1. As translation begins, mRNA, tRNA with bound amino acids, ribosomes, energy
molecules, and protein factors assemble.
2. To initiate translation, the mRNA leader sequence binds to rRNA in the small subunit
of a ribosome, and the first codon attracts a tRNA to form the initiation complex.
3. In elongation, the large ribosomal subunit attaches to the initiation complex. Then the
large ribosomal subunit attaches and tRNAs bring in amino acids. The tRNA anticodons
bind their codons in the mRNA, bringing in amino acids that align. Then peptide bonds form
between the amino acids, building a polypeptide.
4. Protein synthesis halts when a stop codon is reached.
5. Translation is efficient and economical, because RNA, ribosomes, enzymes, and key
proteins are recycled. Transcription produces many copies of an mRNA, and each
mRNA can bind dozens of ribosomes.

10.3 Processing a Protein

1. A protein folds into its three-dimensional conformation as translation proceeds, which

is essential for its function.
2. The primary structure is the sequence of amino acids, which determines the
secondary structure, which consists of closely-knit folded sheets, loops, coils,
barrels, and helices.
3. The primary and secondary structures, in turn, enable the protein to fold into complex
three-dimensional shapes (tertiary structure).
4. Some proteins consist of two or more polypeptides joined into a quaternary structure.
5. Mutations in DNA may result in errors in protein sequence and conformation.

Protein Folding and Misfolding

1. Enzymes and chaperone proteins assist growing amino acid chains in assuming their
final functional (three-dimensional) conformations.
2. Signal sequences guide forming proteins to particular sites within the cell, such as
the secretory network.
3. Chaperone proteins stabilize partially folded parts of proteins, assisting them in
attaining the correct conformation.
4. Proteasomes identify and degrade misfolded or excess proteins.
5. Malfunctioning proteasomes lead to protein aggregation that can cause disease.

Prion Diseases

1. A protein can fold into more than one conformation. A misfolded protein that is
infectious is called a prion.
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
2. Prion diseases cause brain degeneration.

IDEAS FOR CLASSROOM DISCUSSION

1. Consult the rare disease websites listed for previous chapters. Have students
describe an inborn error of metabolism and identify the protein that is absent or
abnormal.
2. Skip ahead to Chapter 20 and discuss how enzyme replacement therapy works.
Find information about a disease that is treated this way.
3. Research the RNA Tie club. Discuss the fact that no women were involved.
4. Discuss how researchers used actual experiments and thought experiments to
decipher the genetic code.
5. Find examples in the popular media about individuals having their own genetic
codes, and discuss how this is incorrect. (This won’t be hard to do!) What is really
meant? Why would a headline trumpeting “cracking the genetic code” as news be
incorrect?
6. The author uses parts of the genetic code for passwords! An example: 19CAUhis53
means the structure of DNA was published in 1953, and a codon for histidine is
CAU. Have the class come up with their own passwords.
7. In an episode of TV show The X-Files, agent Skully studied alien genetic material. It
had 5 types of nucleotide bases. Have students invent a genetic code.

DNA SCIENCE BLOG POSTS (http://blogs.plos.org/dnascience/)

Black Pee Disease Offers New View of Arthritic Joints

http://blogs.plos.org/dnascience/2014/09/11/black-pee-disease-offers-new-view-arthritic-
joints/

How Ebola Kills

http://blogs.plos.org/dnascience/2014/08/14/ebola-kills/

Celebrating DNA Day, 2014

http://blogs.plos.org/dnascience/2014/04/24/celebrating-dna-day-2014/

WEBSITES

“The Genetic Codes” (http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi) allows

students to explore organisms and organelles that use slight variations on the nearly-
universal genetic code.

Francis Crick remembers the “RNA Tie Club.”

http://www.webofstories.com/play/francis.crick/84;jsessionid=6E36C3D8632D32C0DD0
AE5DDE97FD2C1

Dr. Marshall Nirenberg on deciphering the genetic code.

http://www.youtube.com/watch?v=8NIcBtTKLy0
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
Ribosome-targeting antibiotics and mechanisms of bacterial resistance
http://www.nature.com/nrmicro/journal/v12/n1/full/nrmicro3155.html Many antibiotic
drugs work because their ribosomes are different from ours. Understanding these
distinctions is important in developing new drugs to combat multidrug resistant bacterial
infections.

Protein misfolding diseases http://neurophage.com/science/protein-misfolding-diseases/

Prion diseases, from the Centers for Disease Control and Prevention
http://www.cdc.gov/ncidod/dvrd/prions/

ANSWERS TO REVIEW QUESTIONS

1. a. H bonds between A and T and G and C join the strands of the double helix.
b. In DNA replication, a new strand is synthesized semi-conservatively, with new
bases inserted opposite their complementary bases to form a new strand.
c. An mRNA is transcribed by aligning RNA nucleotides against their complements
in one strand of the DNA.
d. The sequence preceding the protein-encoding sequence of the mRNA base pairs
with rRNA in the ribosome.
e. A tRNA binds to mRNA by base pairing between the 3 bases of its anticodon and
the 3 mRNA bases of a codon.
f. The cloverleaf of tRNA arises from H bonding between complementary bases.

2. The direction of the flow of genetic information in retroviruses is opposite that of the
central dogma.

3. a. Adds RNA nucleotides to the growing RNA molecule.

b. Binds misfolded proteins to mark them for refolding or destruction.
c. Assists an amino acid chain in assuming its final functional conformation.
d. Binds DNA at the promoter, attracts and binds RNA polymerase, which begins
transcription.

4. Hydrogen bonds form between RNAs and peptide bonds form between amino acids.

5. RNA contains ribose and uracil and is usually single-stranded. DNA contains
deoxyribose and thymine and is double-stranded. DNA preserves and transmits
genetic information; RNA expresses genetic information to manufacture proteins.

6. DNA replication occurs in the nucleus. Prokaryotes have no nucleus so replication

and transcription occur in the cytoplasm. Translation occurs in the cytoplasm of all
cell types. In eukaryotes, some ribosomes are attached to the ER.

7. Transcription controls cell specialization by turning different sets of genes on and off
in different cell types.

8. The same mRNA codon can be at the A site and the P site because the ribosome
moves.

Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
9. In transcription initiation, the DNA double helix unwinds locally, transcription factors
bind near the promoter, and RNA polymerase binds to the promoter.

10. mRNA is the intermediate between DNA and protein, carrying genetic information to
ribosomes. tRNA connects mRNA to amino acids, and transfers amino acids to
ribosomes for incorporation into protein. rRNA associates with proteins to form
ribosomes.

11. Adding a cap and poly A tail and removing introns.

12. Ribosomes consist of several types of proteins and rRNAs assembled into two
subunits of unequal size.

13. An overlapping code constrains protein structure because certain amino acids would
always be followed by the same amino acids in every protein.

14. A 2-nucleotide code would encode 16 different amino acids, and there are 20 in life.

15. Transcription and translation recycle tRNAs and ribosomes. Many transcripts are
made at a time, and mRNAs are used over and over.

16. The amino acid sequence determines a protein's conformation by causing attractions
and repulsions between different parts of the molecule.

17. The primary structure creates attractions and repulsions between different parts of
the molecule. This results in a secondary structure of helices, sheets, or various
distinct shapes which give a larger tertiary structure. When more than one
polypeptide unit bonds, a complex quaternary structure forms which may be large.

18. A protein is “infectious” when it converts another non-infectious protein into the
infectious conformation with touch.

ANSWERS TO APPLIED QUESTIONS

1. A A U G U G A A C G A A C U C U C A G

2. C G A T A G A C A G T A T T T T C T C C T

3. Answers combine his (CAU or CAC), ala (CGU, GCC, GCA, GCG), arg (CGU, CGC,
CGA, CGG), ser (AGU, AGC, AGA, AGG), leu (CUU, CUC, CUA, CUG), val (GUC,
GUG) and cys (UGU, UGC).

4. Several answers are possible because of the redundancy of the genetic code. One
answer is: C A T A C C T T T G G G A A A T G G

5. There is only one genetic code.

6. 26,927

Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
7. 125, but this doesn’t account for synonymous codons.

8. 1

9. Alternative splicing of the insulin receptor pre-mRNA.

10. The jarring motions that happen during football and combat may cause and then
stabilize a protein capable of forming prions to do so. As prions clog proteasomes,
other types of proteins can no longer be processed either, leading to brain
degeneration.

11. a. G A A A A C C U U b. glu-asn-leu

12. a. AAA to ACA b. UCA to CUA c. GCU to GUU

13. a. nonsynonymous b. GAU to AAU and GAC to AAC c. in the brain

ANSWERS TO WEB ACTIVITIES

1. Many technical articles are behind paywalls, but students can answer the question
using the abstracts at NCBI.

Alzheimer disease: disrupted protein repair and degradation and protein

oxidation.http://www.ncbi.nlm.nih.gov/pubmed/21383047

Parkinson disease: protein misfolding and aggregation, resulting in inclusion bodies and
other aggregates within cells http://www.ncbi.nlm.nih.gov/pubmed/15564047

Huntington disease: clearance of Huntington protein.

http://www.ncbi.nlm.nih.gov/pubmed/21145396

ALS: proteasomes, not autophagy in lysosomes, causes ALS.

http://www.ncbi.nlm.nih.gov/pubmed/23095749

Lewy body dementia: a proteasome component is reduced in LBD but not in the similar
Alzheimer disease. http://www.ncbi.nlm.nih.gov/pubmed/18401540

ANSWERS TO CASE STUDIES AND RESEARCH RESULTS

1. a. Shortens b. No change. c. Shortens d. Lengthens. e. No protein made

2. Alternate splicing of pre-mRNA.

3. tRNA

4. A prion formed and became active.

Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
ANSWERS TO KEY CONCEPTS QUESTIONS

10.1
1. RNA differs from DNA in that it is generally single-stranded, has uracil instead of
thymine, and has the sugar ribose instead of deoxyribose.
2. Each contiguous 3 bases of an mRNA encode an amino acid.
3. Transfer RNAs bring amino acids to the complementary 3-base sequence (the
codon) on the mRNA.
4. Transcription factors bind a promoter sequence in the DNA, which attracts RNA
polymerase. Then DNA unwinds locally, and RNA polymerase attaches RNA
bases that are complementary to the template strand of the DNA. A termination
sequence in the DNA ends the process.
5. Alternate splicing refers to combining the exons of a gene in different ways, to
form slightly different versions of a protein.

10.2
1. The genetic code is triplet, usually nonoverlapping, universal, and degenerate.
2. In translation initiation, the mRNA leader sequence binds to rRNA in the small
ribosomal subunit and the first codon attracts a tRNA. Then the large ribosomal
subunit attaches and tRNAs bring in amino acids, with the tRNA anticodon
binding their codons in the mRNA. Peptide bonds form between the amino acids
attached to the aligned tRNAs, building a polypeptide. Protein synthesis halts at
a stop codon.
3. RNA, ribosomes, enzymes, and key proteins are recycled. Transcription
produces many copies of an mRNA, and each mRNA can bind several
ribosomes.

10.3
1. The primary sequence of a protein largely determines the way that it folds into
small-scale local motifs (secondary structure) as well as larger-scale three-
dimensional forms. Chaperone proteins assist in protein folding.
2. Proteasomes are spool-like structures that function like a wood chipper in
destroying misfolded proteins.
3. A prion is a conformation of a protein that can make other copies of that protein
folded into non-infectious forms become infectious. Prions cause similar brain
diseases in different mammalian species.

ADDITIONAL QUESTIONS

1. In the autosomal recessive polyglandular syndrome, the immune system attacks

several glands, causing hair and nail loss, high blood sugar, disrupted calcium
metabolism, slow metabolism, chronic yeast infections in the mouth, flaky skin, and
loss of skin pigment. The responsible mutation changes a CGA DNA triplet to TGA,
and the gene encodes a transcription factor.
a. How is the protein gene product abnormal?
b. How can one gene exert such varied effects?

2. Apolipoprotein B carries cholesterol and is manufactured in the liver and small

intestine. Liver cells secrete a long form, and cells in the small intestine secrete a
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
 short form by changing a CAA mRNA codon into a stop codon. What is the base
change?

3. A controversial hypothesis proposes that many cases of Alzheimer disease are not
inherited, because the sequences of genes known to cause the disorder are wild
type. However, the mRNA from these genes can contain errors that cause the build-
up of gummy amyloid protein in the brain that characterizes the disease. What
process must be disrupted for this to occur?

4. A gene consisting of 4,892 nucleotides encodes a protein of 1455 amino acids.

Account for the extra DNA bases.

5. mRNA encoding a type of keratin protein is found in the cornea, but not elsewhere.
What does this mean?

6. Explain why a mutation that disrupts the reading frame would likely be devastating.

7. Why might disabling proteasomes cause symptoms of more than one disease?

ANSWERS TO ADDITIONAL QUESTIONS

1. a. The protein is shortened.

b. A transcription factor affects the expression of several other genes, causing
different symptoms.

2. CAA changed to UAA, which is a stop codon.

3. The error must be in transcription.

4. Extra DNA bases are introns.

5. The gene is expressed only in the cornea.

6. Disrupting the reading frame alters multiple amino acids in the encoded protein.

7. A disabled proteasome could not process any protein, not just the one associated
with a particular disease.

Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the
prior written consent of McGraw-Hill Education.
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