Question

Introduction to Gene Expression
Excerpted and adapted from Carl Zimmer, “How One Child’s
Sickle Cell Mutation Helped Protect the World from Malaria.”
From The New York Times. © 2018 The New York Times
Company. All rights reserved. Used under license.
The Origins of Sickle Cell Anemia
1 Over 7,000 years ago, a special child was born
in the Sahara in Africa. At the time, this was
not a desert; it was a green belt of savannas,
woodlands, lakes, and rivers. Bands of hunter-
gatherers thrived there, catching fish and spearing
hippos. A genetic mutation had altered the child’s
hemoglobin, the molecule in red blood cells
that ferries oxygen through the body. It was not
harmful; there are two copies of every gene, and
the child’s other hemoglobin gene was normal.
The child survived, had a family, and passed down
the mutation to future generations.
2 As the greenery turned to desert, the descendants
of the hunter-gatherers became cattle-herders and
farmers and moved to other parts of Africa. The
mutation endured over generations, and for good
reason. People who carried one mutated gene
were protected against one of the biggest threats
to humans in the region: malaria. There was just
one problem with this genetic advantage: From
time to time, two descendants of that child would
meet and start a family. Some of their children
inherited two copies of the mutant hemoglobin
gene instead of one. These children could no
longer produce normal hemoglobin. As a result,
their red blood cells took on a sickle shape and
became defective, and this led to clogged blood
vessels. The condition, now known as sickle cell
anemia, leads to extreme pain, difficulty with
breathing, kidney failure, and even strokes.
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3 Today, over 250 generations later, the sickle
cell mutation has been inherited by millions of
people. While the majority of carriers live in
Africa, many others live in southern Europe,
the Near East, and India. Those carriers have
about 300,000 children each year with sickle cell
anemia. Today, sickle cell anemia remains a heavy
burden on public health. In many poor countries,
most children with the disease still die young.
However, access to improved healthcare in some
nations, such as the United States, has increased
the life expectancy for people with sickle cell
disease.
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Flow Charts
FLOW CHART OF TRANSCRIPTION
FLOW CHART OF TRANSLATION
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Decoding the Sickle Cell Mutation
U
U
UAU
UAC
UAA
UAG
Tyr
Stop
Stop
UGU
UGC
UGA
UGG
Cys
Stop
Trp
CGU
CGC
CGA
CGG
Arg
CAU
CAC
CAA
CAG
His
Gln
AAU
AAC
AAA
AAG
Asn
Lys
AGU
AGC
AGA
AGG
Ser
Arg
GAU
GAC
GAA
GAG
Asp
Glu
Ser
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
Pro
ACU
ACC
ACA
ACG
Thr
GCU
GCC
GCA
GCG
Ala
GGU
GGC
GGA
GGG
Gly
UUU
UUC
UUA
UUG
Phe
Leu
Leu
CUU
CUC
CUA
CUG
Ile
Met
AUU
AUC
AUA
AUG
Val
GUU
GUC
GUA
GUG
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
C
Second position
First position [5’ end]
Third position [3’ end]
A G
Amino acid chart
1. Examine the partial DNA sequences in the tables below. Then do the following:
(a) Transcribe the partial DNA sequences.
(b) Translate the partial RNA sequences by referencing the amino acid chart
above.
(c) Compare the amino acid sequences and circle any differences in the second
table.
PARTIAL SEQUENCE OF
TYPICAL β-GLOBIN GENE
Partial DNA Sequence T GAGGAC T C C T C
mRNA Sequence
Amino Acid Sequence
PARTIAL SEQUENCE OF
SICKLE CELL β-GLOBIN GENE
Partial DNA Sequence T GAGGAC AC C T C
mRNA Sequence
Amino Acid Sequence
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2. DNA is a double-stranded molecule, so why is only one strand shown in the
tables?
3. How could the changes made to the amino acid sequence influence phenotype
changes?

Answer 1

1. Transcription and translation (showing the changed codon)

- Typical β‑globin (relevant codon):
- DNA (coding strand): ...GAG...
- mRNA (replace T → U on coding strand): ...GAG...
- Amino acid: GAG → Glutamic acid (Glu, E)

- Sickle‑cell β‑globin (single base change in the same codon):
- DNA (coding strand): ...GTG...
- mRNA: ...GUG...
- Amino acid: GUG → Valine (Val, V)

Difference to circle in the amino‑acid sequence: Glu (E) → Val (V) at that one position.

(If you transcribe the whole short sequences given in the handout by using the coding strand as shown and replacing T with U, you will get the mRNA that includes the codon change above. Translation of that codon gives the single amino‑acid difference shown.)

2. Why only one DNA strand is shown?
DNA is double‑stranded, but when showing a gene sequence it is common to show only the coding (sense or non‑template) strand. The mRNA sequence is identical to the coding strand except T is replaced by U, so showing the coding strand is enough for transcription/translation exercises.

3. How the amino‑acid change can influence phenotype
- Chemical difference: Glutamic acid is polar and negatively charged; valine is nonpolar and hydrophobic. Replacing Glu with Val changes the local chemistry of the protein.
- Structural/functional consequence: That single substitution makes deoxygenated hemoglobin stick to other hemoglobin molecules, forming long fibers. These fibers distort red blood cells into the sickle shape.
- Physiological effects: Sickle cells are fragile and block small blood vessels, causing anemia, pain crises, organ damage and reduced oxygen delivery.
- Population effect: Although harmful in homozygotes (two mutant copies), heterozygotes (one mutant copy) have some resistance to malaria, which explains why the mutation persists at higher frequency in some populations.