CHAPTER 3 Flashcards
(150 cards)
1
Q
a gene participates in three major activities:
- A gene is a ______ of information. That is, it holds the information for making one of the key molecules of life, an _____. The sequence of bases in the RNA depends directly on the sequence of bases in the gene. Most of these RNAs, in turn, serve as templates for making other critical cellular molecules, proteins. The production of RNAs and proteins from a DNA blueprint is called _______.
A
repository ; RNA ; gene
expression
2
Q
a gene participates in three major activities:
- A gene can be ______. This duplication is very _____, so the genetic information can be passed essentially unchanged from generation to generation.
A
replicated ; faithful
3
Q
a gene participates in three major activities:
- A gene can accept ______ or _____. This allows organisms to evolve. Sometimes, these changes involve recombination, exchange of DNA
between chromosomes or sites within a chromosome. A subset of recombination events involve
pieces of DNA (transposable elements) that move from one place to another in the genome.
A
occasional changes, or mutations ;
4
Q
(OVERVIEW OF GENE EXPRESSION)
As we have seen, producing a protein from information in a DNA gene is a two-step process.
The first step is synthesis of an RNA that is complementary to one of the strands of DNA called _______
In the second step, called ________, the information in the RNA is used to make a polypeptide. Such an informational RNA is called a _______ to denote the fact that it carries information —like a message —from a gene to the cell ’s protein factories
A
transcription ; translation ; messenger RNA (mRNA)
5
Q
Like DNA and RNA, ______ are polymers —long, chain-like molecules.
A
proteins
6
Q
The monomers, or links, in the protein chain are called ________
A
amino acids.
7
Q
DNA and protein have this informational relationship: Three nucleotides in the DNA gene stand for _________
A
one amino acid in a protein.
8
Q
The codeword (or _____) for methionine in this mRNA is the triplet _____; similarly, the codons for serine, asparagine, and alanine are _____, _____, and ____ respectively
A
codon ; AUG ; AGU, AAC, and GCG,
9
Q
The bottom DNA strand is complementary to the mRNA, which serve as the template for making the mRNA. Thus, we call the bottom strand the ________, or the ________
A
template strand ; transcribed strand
10
Q
The top strand is the _________ or the __________.
A
nontemplate strand ; non-transcribed strand
11
Q
The top strand has essentially the same coding properties as the corresponding mRNA, many geneticists call it the _______ and the opposite strand would therefore be the ________.
A
coding strand ; anti coding strand
12
Q
Since the top strand has the same sense as the mRNA, this same system of nomenclature refers to this top strand as the ________, and to the bottom strand as the _________.
A
sense strand ; antisense strand
13
Q
“coding strand ” and “sense strand” are opposite, so to avoid confusion, the terms _________ and ________ is used.
A
“template strand” ; “nontemplate strand”
14
Q
(PROTEIN STRUCTURE)
_______, like nucleic acids, are chain-like polymers of small subunits.
A
Proteins
15
Q
In DNA and RNA, the links in the chain are ________.
A
nucleotides
16
Q
The chain links of proteins are __________
A
amino acids
17
Q
DNA contains only four different _______
A
nucleotides
18
Q
Proteins contain ___ different amino acids
A
20
19
Q
Each amino acid has:
an _____ (NH3 +)
a ______ (COO2)
a ______ (H),
and ______ where the difference between 2 amino acids is their side chain (it is the arrangement as well the distinct side chain that makes protein unique)
A
amino group ; carboxyl group ; hydrogen atom ; side chain
20
Q
The amino acids join together in proteins via ________ which gives rise to the name ________ for a chain of amino acids.
A
peptide bonds ; polypeptide
21
Q
A polypeptide chain has ______, just as the DNA chain does.
A
polarity
22
Q
The dipeptide (two amino acids linked together) has a free amino group at its left end which is the _______ or ______. It also has a free carboxyl group at its right end, which is the ________ or _________
A
amino terminus, or N-terminus ; carboxyl terminus, or C-terminus.
23
Q
The linear order of amino acids constitutes a protein’s _________.
A
primary structure
24
Q
The way these amino acids interact with their neighbors gives a protein its ________
A
secondary structure.
25
The ______ is a common form of secondary structure. It results from hydrogen bonding among near-neighbor amino acids.
a-helix
26
___________ is another common secondary structure found in proteins which involves extended protein chains, packed side by side, that interact by _______. The packing of the chains next to each other creates the sheet apperance — _____ is a protein very rich in B-pleated sheets
B-pleated sheet ; hydrogen bonding ; silk
27
third example of secondary structure is _____ — connects the a-helices and B- pleated sheet elements in a protein.
turn
28
The total three-dimensional shape of a polypeptide is its ________
tertiary structure
29
Elements of secondary structure are apparent, especially the several a-helices of the molecule. Note the overall roughly spherical shape of myoglobin. Most polypeptides take this form, which we call _____.
globular
30
ribbon model depicts the tertiary structure of an enzyme known as ________ or ____________
GAMT or the guanidinoacetate methyl transferase.
31
three types of secondary structure:
- a- helices, represented by ________;
- b- pleated sheets, represented by _____ laid side by side;
- and ______ between the structural elements, represented by strings.
- helical ribbons
- flat arrows
- turns
32
Both ______ and ______ are composed of a single, more or less globular, structure, but other proteins can contain more than one compact structural region where each of these regions is called a ______
myoglobin and GAMT ; domain
33
______ or the proteins that white blood cells make to repel invaders provide a good example of domains.
Antibodies
34
Each of the four polypeptides in the IgG- type antibody contains __________
domains contain common structural- functional motifs such as finger-shaped motif called a _____ that is involved in DNA binding.
- globular domains.
- zinc finger
35
The highest level of protein structure — _________ — which is the way two or more individual polypeptides fit together in a complex protein
quaternary structure
36
The forces that hold a protein in its proper shape are _______, but most are noncovalent.
covalent bonds
37
The principal covalent bonds within and between polypeptides are __________ between cysteines.
disulfide (S–S) bonds
38
The noncovalent bonds are primarily _______ and ________
hydrophobic and hydrogen bonds
39
__________ cluster together in the interior of a polypeptide, or at the interface between polypeptides, so they can avoid contact with water (hydrophobic, meaning water-fearing).
Hydrophobic amino acids
40
______________ play a major role in tertiary and quaternary structures of proteins.
Hydrophobic interactions
41
(PROTEIN FUNCTION)
Some proteins provide the structure that helps give cells _____ and ______
ntegrity and shape
42
Other proteins serve as _______ to carry signals from one cell to another.
hormones
43
________ can also bind and carry substances.
Proteins
44
The __________ carries oxygen from the lungs to remote areas of the body.
protein hemoglobin
45
________ stores oxygen in muscle tissue until it is used.
Myoglobin
46
_______ also control the activities of genes.
Proteins
47
_________ serve as enzymes that catalyze the hundreds of chemical reactions necessary for life.
Proteins
48
(THE RELATIONSHIP BETWEEN GENES AND PROTEINS)
1902, ________ noticed that a human disease, _______ behaved as if it were caused by a single recessive gene
Archibald Garrod ; alcaptonuria
49
Patients with alcaptonuria excrete copious amounts of _________, which has the startling effect of coloring their urine black
homogentisic acid
50
Garrod reasoned that the abnormal buildup of this compound resulted from a ____________
defective metabolic pathway.
51
Somehow, a blockage somewhere in the _______ was causing the intermediate, homogentisic acid, to accumulate to abnormally high levels, much as a dam causes water to accumulate behind it.
pathway
52
Several years later, Garrod proposed that the problem came from a defect in the pathway that degrades the amino acid ___________
phenylalanine
53
By that time, metabolic pathways had been studied for years and were known to be controlled by enzymes — ___________. Thus, it seemed that alcaptonuria patients carried a defective _______
one enzyme catalyzing each step ; enzyme
54
Because the disease was inherited in a simple Mendelian fashion, Garrod concluded that a gene must control the enzyme ’s production so when that gene is defective, it gives rise to a __________
defective enzyme
55
1940s, ______ and _______, carried the argument further with their studies of a common bread mold, the _________
George Beadle and E.L Tatum ; Neurospora crassa
56
They performed their experiments as follows:
First, they bombarded the ______ (spore-forming parts) of Neurospora with ______ to cause mutations.
Then, they collected the spores from the irradiated mold and germinated them separately to give pure strains of ______.
They screened many thousands of strains to find a _______.
The mutants revealed themselves by their inability to grow on minimal medium composed only of ______, _____, ____ and _______
Wild-type Neurospora grows readily on such a medium; the mutants had to be fed something extra —a _______, for example —to survive.
- peritheca ; x-rays
- mold
- few mutants
- sugar, salts, inorganic nitrogen, and the vitamin biotin.
- vitamin
57
Next, Beadle and Tatum performed biochemical and genetic analyses on their mutants. By carefully adding ______, one at a time, to the mutant cultures, they pinpointed the biochemical defect.
For example, the last step in the synthesis of the vitamin pantothenate involves putting together the two halves of the molecule: pantoate and b-alanine where one “pantothenateless” mutant would grow on pantothenate, but not on the two halves of the vitamin. This demonstrated that the last step (step 3) in the biochemical pathway leading to pantothenate was blocked, so the _______________.
The genetic analysis was just as straightforward. Neurospora is an ascomycete, in which nuclei of two different mating types fuse and undergo meiosis to give eight haploid ascospores, borne in a fruiting body called an _____.
Beadle and Tatum collected the spores, germinated them separately, and checked the phenotypes of the resulting molds and they found that four of the eight spores gave rise to mutant molds, demonstrating that the mutant phenotype was controlled by a _______
The event happened over and over again, leading these investigators to the conclusion that each enzyme in a biochemical pathway is controlled by one gene.
__________ - a subsequent work has shown that many enzymes contain more than one polypeptide chain and that each polypeptide is usually encoded in one gene.
- substances
- enzyme that carries out that step must have been defective
- ascus
- single gene.
- one-gene/one-polypeptide hypothesis
58
(DISCOVERY OF MESSENGER RNA)
______ carry information from gene to ribosome.
mRNA
59
1958, Crick proposed that ______ serves as an intermediate carrier of genetic information where he based his hypothesis in part on the fact that the DNA resides in the nucleus of eukaryotic cells, whereas ______ are made in the cytoplasm which means that something must carry the information from one place to the other
RNA ; proteins
60
Crick noted that ribosomes contain RNA and suggested that this _________ is the information bearer.
ribosomal RNA (rRNA)
61
________ proposed an alternative hypothesis calling for nonspecialized ribosomes that translate unstable RNAs called _________ — are independent RNAs that bring genetic information from the genes to the ribosomes.
François Jacob and colleagues ; messengers
62
1961, ____, ______, and _____, published their proof of the messenger hypothesis.
Jacob, Sydney Brenner and Mathew Meselson
63
The premise of the experiments was this: When phage ____ infects E. coli, it subverts its host from making bacterial proteins to making _____
If Crick’s hypothesis were correct, this switch to phage protein synthesis should be accompanied by the production of new ______ equipped with phage- specific RNAs
T2 ; phage proteins
ribosomes
64
To distinguish new ribosomes from old, these investigators labeled the ribosomes in uninfected cells with heavy isotopes of ________ and ________.
This made “_____” ribosomes heavy. Then they infected these cells with phage T2 and simultaneously transferred them to medium containing light nitrogen (14 N) and carbon (12 C).
Any “_____ ” ribosomes made after phage infection would therefore be light and would separate from the old, heavy ribosomes during ________
- nitrogen (15 N) and carbon (13 C)
- old
- new ; density gradient centrifugation.
65
________ also labeled the infected cells with 32P to tag any phage RNA as it was made.
Brenner and colleagues
66
Then they asked this question: Was the radio actively labeled phage RNA associated with new or old ribosomes?
It was shown that the phage RNA was found on _______ whose rRNA was made before infection even began.
Clearly, this old rRNA could not carry phage genetic information; by extension, it was very unlikely that it could carry host genetic information, either. Thus, the ______ are constant.
- old ribosomes
- ribosomes
67
_______, unlike host rRNA, has a base composition similar to that of host DNA. This lends further weight to the hypothesis that _____, not rRNA, is the informational molecule.
Host mRNA ; mRNA
68
(TRANSCRIPTION)
Transcription follows the same base pairing rules as DNA replication: _______ in the DNA pair with ________ respectively, in the RNA product.
T, G, C, and A ; A, C, G, and U,
69
Highly directed chemical reactions such as transcription do not happen at significant rates by themselves—they are enzyme-catalyzed and the enzyme that directs transcription is called ________.
RNA polymerase
70
THREE PHASES OF TRANSCRIPTION
1. Initiation
2. Elongation
3. Termination
71
(iNITIATION)
First, the enzyme recognizes a region called a _______, which lies just “upstream” of the gene. The polymerase binds tightly to the promoter and causes localized melting, or separation, of the two DNA strands within the promoter. At least ______ are melted.
Next, the polymerase starts building the RNA chain. The substrates, or building blocks, it uses for _____, ______, _____ and ______.
- promoter ; 12 bp
- ATP, GTP, CTP, and UTP.
72
The first, or initiating, substrate is usually a _______.
After the first nucleotide is in place, the polymerase joins a second nucleotide to the
first, forming the initial _______ in the RNA chain. Several nucleotides may be joined before the polymerase leaves the promoter and elongation begins.
- purine nucleotide
- phosphodiester bond
73
(ELONGATION)
During the elongation phase of transcription, ________ directs the sequential binding of ribonucleotides to the growing RNA chain in the 5’ → 3’ direction (from the 5’-end toward the 3’-end of the RNA).
As it does so, it moves along the _______, and the “_____" of melted DNA moves with it. This melted region exposes the bases of the template DNA one by one so they can pair with the bases of the incoming ribonucleotides.
As soon as the transcription machinery passes, the two DNA strands wind around each other again, re-forming the _______
- RNA polymerase
- DNA template ; bubble
- double helix
74
This points to two fundamental differences between transcription and DNA replication:
(a) ________makes only one RNA strand during transcription, which means that it copies only one DNA strand in a given gene. (However, the opposite strand may be transcribed in another gene.) Transcription is therefore said to be _________. This contrasts with semiconservative DNA replication, in which both DNA strands are copied.
(b) In transcription, DNA melting is limited and transient. Only enough strand separation occurs to allow the polymerase to “read ” the DNA template strand. However, during replication, the two parental DNA strands ___________.
(a) RNA polymerase ; asymmetrical
(b) separate permanently
75
(TERMINATION)
Just as promoters serve as initiation signals for transcription, other regions at the ends of genes, called ________, signal termination.
These work in conjunction with RNA polymerase to loosen the association between _______ and _______
The result is that the RNA dissociates from the RNA polymerase and DNA, thereby _________
- terminators
- RNA product and DNA template.
- stopping transcription
76
RNA sequences are usually written ______, left to right. This feels natural to a molecular biologist because RNA is made in a 5’-to-3’ direction.
5’ to 3’
77
mRNA is also translated _________. Thus, because ribosomes read the message 5’ to 3’, it is appropriate to write it 5’ to 3’ so that we can read it like a sentence.
5’ to 3’
78
Genes are also usually written so that their transcription proceeds in a __________ direction.
left-to-right
79
This “______” of transcription from one end to the other gives rise to the term _______, which refers to the DNA close to the start of transcription (near the left end when the gene is written conventionally).
flow ; upstream
80
Thus, we can describe most promoters as lying just _______ of their respective genes.
upstream
81
By the same convention, we say that genes generally lie _______ of their promoters.
downstream
82
Genes are also conventionally written with their _________ on top.
nontemplate strands
83
(TRANSLATION)
TWO SUBSTANCES THAT PLAY KEY ROLES IN TRANSLATION:
Ribosomes
tRNA
84
protein-synthesizing machines.
Ribosomes
85
Ribosomes 2 subunits
50s and 30s
86
refer to the sedimentation coefficients of the two subunits.
50S and 30S
87
These __________ are a measure of the speed with which the particles sediment through a solution when spun in an ultracentrifuge.
coefficients
88
The ___________, with a larger sedimentation coefficient, migrates more rapidly to the bottom of the centrifuge tube under the influence of a centrifugal force.
50S subunit
89
The ________ are functions of the mass and shape of the particles.
coefficients
90
______ sediment more rapidly than light ones; ______ migrate faster than extended or flattened ones
Heavy particles ; spherical particles
91
The 50S subunit is actually about _____ as massive as the 30S.
twice
92
Together, the 50S and 30S subunits compose a ______ where the numbers do not add up that is because the sedimentation coefficients are not proportional to the particle mass; in fact, they are roughly proportional to the two- thirds power of the particle mass.
70S ribosome
93
Each ribosomal subunit contains ____ and ______.
The _____includes one molecule of ribosomal RNA (rRNA) with a sedimentation coefficient of ____, plus ___ ribosomal proteins.
The ____ is composed of 2 rRNAs (_______) and ___ proteins.
- RNA and protein
- 30S subunit ; 16S ; 21
- 50S subunit ; 23S + 5S ; 34
94
________ are gene products thus, a ribosome is produced by dozen of genes.
Ribosomal proteins
95
_____ participate in protein synthesis but do not code for proteins.
rRNAs
96
_______ is the only step in expression of the genes for rRNAs, aside from some trimming of the transcripts.
Transcription
97
the adapter molecule
tRNA
98
The adapter molecule in translation is indeed a small RNA that recognizes both RNA and amino acids; it is called __________
transfer RNA (tRNA).
99
the molecule has two “business ends.”
One end (the ____ of the model) attaches to an amino acid. Because this is a tRNA specific for ______, only _______ will attach. An enzyme called ______ catalyzes this reaction. The generic name for such enzymes is _________
The other end (the _____ of the model) contains a 3-bp sequence that pairs with a complementary 3-bp sequence in an mRNA. Such a triplet in mRNA is called a _____; naturally enough, its complement in a tRNA is called an ______.
- top ; phenylalanine (tRNA Phe) ; phenylalanine-tRNA synthetase ; phenylalanine ; aminoacyl-tRNA synthetase.
- bottom; codon ; anticodon
100
______ contains 3 letter words.
Actually, three of the possible codons (____, _____ and ____) code for termination; that is, they tell the ribosome to stop.
All of the other codons ________. This means that most amino acids have more than one codon; the genetic code is therefore said to be degenerate.
- Genetic code
- UAG, UAA, and UGA)
- specify amino acids
101
(INITIATION OF PROTEIN SYNTHESIS)
three codons terminate _______
translation.
102
three termination codons interact with protein factors, whereas the initiation codon interacts with a special aminoacyl tRNA. In eukaryotes this is methionyl-tRNA (a tRNA with methionine attached); in bacteria it is a derivative called ________ which is just methionyl tRNA with a formyl group attached to the amino group of methionine.
N formylmethionyl-tRNA
103
We find _____ codons not only at the beginning of mRNAs, but also in the middle of messages.
When they are at the beginning, AUGs serve as ________, but when they are in the middle, they simply _______
- AUG
- initiation codons ; code for methionine
104
Bacterial messages have a special sequence, called a ________, named for its discoverers, just upstream of the initiating AUG.
The Shine – Dalgarno sequence attracts _________ to the nearby AUG so translation can begin.
Eukaryotes, by contrast, do not have Shine – Dalgarno sequences. Instead, their mRNAs have a special methylated nucleotide called a _____ at their 5’ends.
A cap-binding protein known as _____ binds to the cap and then helps attract ribosomes.
- Shine–Dalgarno sequence
- ribosomes
- cap
- eIF4E
105
(TRANSLATION ELONGATION)
At the end of the initiation phase of translation, the initiating aminoacyl-tRNA is bound to a site on the ribosome called the _____
P site.
106
For elongation to occur, the ribosome needs to add amino acids one at a time to the __________
initiating amino acid
107
Elongation begins with the binding of the second aminoacyl-tRNA to another site on the ribosome called the ______
A site
108
This process requires an elongation factor called ______, where EF stands for “elongation factor, ” and energy provided by GTP.
EF-Tu
109
Next, a peptide bond must form between the two amino acids. The large ribosomal subunit contains an enzyme known as ________, which forms a peptide bond between the amino acid or peptide in the P site (formylmethionine [fMet] in this case) and the amino acid part of the aminoacyl tRNA in the A site.
peptidyl transferase
110
The result is a ______ in the A site. The dipeptide is composed of fMet plus the second amino acid, which is still bound to its tRNA. The large ribosomal RNA contains the peptidyl transferase active center.
dipeptidyl tRNA
111
The third step in elongation, _________, involves the movement of the mRNA one codon’s length through the ribosome. This maneuver transfers the dipeptidyl-tRNA from the A site to the P site and moves the deacetylated tRNA from the P site to another site, the _____, which provides an exit from the ribosome. Translocation requires another elongation factor called ______ and _______.
translocation ; E site ; EF-G and GTP
112
(TERMINATION OF TRANSLATION AND mRNA STRUCTURE)
Three different codons (____, ____ and _____) cause termination of
UAG, UAA, and UGA
113
Protein factors called _______ recognize these termination codons (or stop codons) and cause translation to stop, with release of the polypeptide chain.
release factors
114
The initiation codon at one end, and the termination codon at the other end of a coding region of a gene identify an ________. It is called “open ” because it contains no _______ to interrupt the translation of the corresponding mRNA.
open reading frame (ORF) ; internal termination codons
115
The “_______ ” part of the name refers to the way the ribosome can read the mRNA in three different ways, or “frames,” depending on where it _____.
reading frame ; starts
116
This _____ (shorter than any gene you would expect to find) contains a start codon (___) and a stop codon (____). (Remember that these DNA codons will be transcribed to mRNA with the corresponding codons AUG and UAG.) In between (and including these codons) we have a short open reading frame that can be translated to yield a tetrapeptide (a peptide containing four amino acids): fMet-Gly-Tyr-Arg.
minigene ; ATG ; TAG
117
_______ may also have more than one open reading frame, but the largest is usually the one that is used.
natural mRNA
118
_____ begins with the first G and _______ begins 9 bp downstream at the start codon (AUG). Thus, the mRNA produced from this gene has a 9-bp leader, which is also called the _____ or ______
Transcription ; translation ; 5’ -untranslated region, or 5’-UTR.
119
Similarly, a _____ is present at the end of the mRNA between the stop codon and the transcription termination site. The trailer is also called the ____ or _____. In a eukaryotic gene, the transcription termination site would probably be farther downstream, but the mRNA would be cleaved downstream of the translation stop codon and a string of A ’s [poly(A)] would be added to the 3’-end of the mRNA. In that case, the trailer would be the stretch of RNA between the stop codon and the poly(A)
trailer ; 3’-untranslated region, or 3’-UTR ;
120
(REPLICATION)
second characteristic of genes is that they _________.
replicate faithfully
121
The Watson–Crick model for DNA replication assumes that as new strands of DNA are made, they follow the usual base-pairing rules of ______ and ______
A with T and G with C.
122
The model also presupposes that the two parental strands _____ and that each then serves as a ______ for a new progeny strand.
separate ; template
123
This is called ________ because each daughter double helix has one parental strand and one new strand.
semiconservative replication
124
In other words, one of the parental strands is _______ in each daughter double helix.
“conserved ”
125
Another potential mechanism is ________, in which the two parental strands stay together and somehow produce another daughter helix with two completely new strands.
conservative replication
126
Another possibility is ________, in which the DNA becomes fragmented so that new and old DNA regions coexist in the same strand after replication.
dispersive replication
127
_______ and ______proved that DNA really does replicate by a semiconservative mechanism.
Matthew Meselson and Franklin Stahl
128
A third characteristic of genes is that they accumulate changes, or _______
mutations
129
By this process, life itself can change, because _____ is essential for evolution.
mutation
130
If a nucleotide in a gene changes, it is likely that a corresponding change will occur in an ______ in that gene’s protein product. Sometimes, because of the degeneracy of the genetic code, a nucleotide change will not affect the protein.
amino acid
131
For example, changing the codon ____ to _____ is a mutation, but it would probably not be detected because both AAA and AAG code for the same amino acid: lysine.
Such innocuous alterations are called _______
AAA to AAG ; silent mutations
132
changed ______ in a gene results in an altered _______ in the protein.
nucleotide ; amino acid
133
This may be harmless if the amino acid change is ______ (e.g., a leucine changed to an isoleucine). But if the new amino acid is much different from the old one, the change frequently impairs or destroys the function of the protein.
conservative
134
An excellent example of a disease caused by a defective gene is ________
sickle cell disease
135
The shape of normal cells is a ______; that is, the disc is concave viewed from both the top and bottom. However, when these people exercise, or otherwise deplete the oxygen in their blood, their red blood cells change dramatically to a _____ or ______
biconcave disc ; sickle, or crescent, shape
136
The _______ cannot fit through tiny capillaries, so they clog and rupture them, starving parts of the body for blood and causing internal bleeding and pain.
sickle cells
137
_______ are so fragile that they burst, leaving the patient anemic. Without medical attention, patients undergoing a sickling crisis are in mortal danger.
Sickle cells
138
(What causes this sickling of red blood cells?)
The problem is in _______, the red, oxygen- carrying protein in the red blood cells.
hemoglobin
139
Normal hemoglobin remains soluble under ordinary physiological conditions, but the hemoglobin in sickle cells precipitates when the blood oxygen level falls, forming _____, _____ that distort the blood cells into the sickle shape.
long, fibrous aggregates
140
(What is the difference between normal hemoglobin (HbA) and sickle cell hemoglobin (HbS)?)
Vernon Ingram answered this question in 1957 by determining the amino acid sequences of parts of the two proteins using a process that was invented by Frederick Sanger and is known as ______.
protein sequencing
141
Ingram focused on the ______ of the two proteins. _________ is one of the two different polypeptide chains found in the tetrameric (four- chain) hemoglobin protein.
b-globin
142
First, Ingram cut the two polypeptides into pieces with an enzyme that breaks selected peptide bonds. These pieces, called ______, can be separated by a two-dimensional method called _______.
peptides ; fingerprinting
143
The peptides are separated in the first dimension by _________
paper electrophoresis
144
Then the paper is turned 90 degrees and the peptides are subjected to _______ to separate them still farther in the second dimension. The peptides usually appear as ____ on the paper.
paper chromatography ; spots
145
Different proteins, because of their different amino acid compositions, give different patterns of spots. These patterns are aptly named _______
fingerprints
146
When Ingram compared the fingerprints of ____ and _____, he found that all the spots matched except for one where his spot had a different mobility in the HbS fingerprint than in the normal HbA fingerprint, which indicated that it had an altered
HbA and HbS
147
(What change in the b-globin gene caused the change Ingram detected in its protein product?)
The two codons for glutamate (Glu) are ____ and ____; two of the four codons for valine (Val) are ____ and _____
GAA and GAG ; GUA and GUG
148
If the glutamate codon in the HbA gene is GAG, a single base change to GTG would alter the mRNA to GUG, and the amino acid inserted into HbS would be ____ instead of _____. A similar argument can be made for a GAA→GTA change.
valine ; glutamate
149
(Why has this deleterious mutation spread so successfully through the population?)
Although the _________ can be lethal, heterozygotes have little if any difficulty because their normal allele makes enough product to keep their blood cells from sickling.
homozygous condition
150
