1. Revision-Molecular Biology
PART-2
Professor (Dr.) NAMRATA CHHABRA
MHPE, MD, MBBS, FAIMER FELLOW
PRINCIPAL-IN-CHARGE, PROFESSOR & HEAD,
DEPARTMENT OF BIOCHEMISTRY
SSR MEDICAL COLLEGE, MAURITIUS
Transcription, Translation, Genetic code and Mutations
Case studies and Multiple-choice questions
3. DNA Transcription
•The synthesis of an RNA molecule from DNA is called Transcription.
• All eukaryotic cells have five major classes of RNA: ribosomal RNA
(rRNA), messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA
and microRNA (snRNA and miRNA).
•The first three are involved in protein synthesis, while the small RNAs are
involved in mRNA splicing and regulation of gene expression.
4. Similarities between Replication and Transcription
The processes of DNA and RNA synthesis
are similar in that they involve-
(1) the general steps of initiation,
elongation, and termination with 5' to
3' polarity;
(2) large, multicomponent initiation
complexes; and
(3) adherence to Watson-Crick base-
pairing rules.
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5. Differences between Replication and Transcription
(1) Ribonucleotides are used in RNA synthesis rather than deoxy
ribonucleotides;
(2) U replaces T as the complementary base pair for A in RNA;
(3) A primer is not involved in RNA synthesis;
(4) Only a portion of the genome is transcribed or copied into RNA,
whereas the entire genome must be copied during DNA replication;
and
(5) There is no proofreading function during RNA transcription.
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6. Template strand
Except for T for U changes, coding strand corresponds exactly to the
sequence of the RNA primary transcript, which encodes the (protein)
product of the gene.
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8. Bacterial DNA-Dependent RNA Polymerase
The DNA-dependent RNA polymerase (RNAP) of
the bacterium Escherichia coli exists as an
approximately 400 kDa core complex consisting
of-
•two identical α subunits,
•similar but not identical β and β ' subunits, and
•an ω subunit and a
•A sigma subunit (σ)
•Beta is thought to be the catalytic subunit.
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9. Bacterial DNA-Dependent RNA Polymerase
• RNAP, a metalloenzyme, also contains two zinc molecules.
• The core RNA polymerase associates with a specific protein factor
(the sigma σ factor) that helps the core enzyme recognize and bind to
the specific deoxynucleotide sequence of the promoter region to
form the preinitiation complex (PIC)
• Bacteria contain multiple factors, each of which acts as a regulatory
protein.
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10. Mammalian DNA-Dependent RNA Polymerases
Mammalian cells possess three distinct nuclear DNA-Dependent RNA
Polymerases
• RNA polymerase I is for the synthesis of r RNA
• RNA polymerase II is for the synthesis of m RNA and miRNA
• RNA polymerase III is for the synthesis of tRNA/5S rRNA, snRNA
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12. Termination of transcription (contd.)
•Beyond the hair pin, the RNA
transcript contains a strings of
Us, the bonding of Us to the
corresponding As is weak.
•This facilitates the dissociation
of the primary transcript from
DNA.
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13. Modifications of primary transcript of mRNA in
prokaryotes
Transcription and translation are coupled in prokaryotic cells
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14. Post Transcriptional modifications of
Ribosomal RNA (r- RNA)
• The 23S,16S, and 5S ribosomal RNAs of prokaryotes are produced form a single
RNA precursor molecule
• Cleavage and trimming are the mechanisms involved,
• Similar modifications are observed in the processing of eukaryotic r-RNA.
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15. Post Transcriptional modifications of
Transfer RNA(t- RNA)
The extra nucleotides at both 5'
and 3' ends of t- RNA are
removed, an intron from the
anticodon arm is removed,
bases are modified and CCA
arm is attached to form the
mature functional t RNA.
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16. Post Transcriptional modifications of
pre m- RNA
•The addition of the Guanosine
triphosphate (part of the cap is catalyzed
by the nuclear enzyme guanylyl
transferase.
•Methylation of the terminal guanine
occurs in the cytoplasm. and is catalyzed
by guanine-7-methyl transferase.
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18. Post Transcriptional modifications of
Pre m RNA
Introns are removed from the primary transcript in the nucleus, exons
(coding sequences) are ligated to form the mRNA molecule
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20. Clinical significance of Splicing
1) Antibodies against snRNPs
In systemic Lupus Erythematosus (SLE), an auto
immune disease, the antibodies are produced
against host proteins, including sn RNPs.
• 2) Mutations at the splice site
• Mutations at the splice site can lead to improper
splicing and the production of aberrant proteins .
• For example, some cases of Beta thalassemia are as
a result of incorrect splicing of beta globin m- RNA
due to mutation at the splice site.
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21. Biological significance of Splicing
Tissue specific proteins are produced from the same primary transcript by
alternative splicing 2112-Jan-21 Our Biochemistry- Namrata Chhabra
22. Inhibitors of Transcription
• Rifampicin- binds with Beta subunit of prokaryotic
RNA polymerase,
• It is an inhibitor of prokaryotic transcription initiation.
• It binds only to bacterial RNA polymerase but not to
eukaryotic RNA polymerases.
• Therefore, Rifampicin is a powerful drug for treatment
of bacterial infections.
• Used for the treatment of tuberculosis and leprosy
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23. Mechanism of action of Actinomycin D
• Actinomycin D- Intercalates with DNA strands
• Actinomycins inhibit both DNA synthesis and RNA
synthesis by blocking chain elongation.
• They interact with G·C base pairs as they require
the 2-amino group of guanine for binding.
• Actinomycins are used as anticancer drugs
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24. Mitomycin and Alpha amanitin
• Mitomycin- Intercalates with DNA strands
• blocks transcription,
• used as anticancer drug
• Alpha amanitin is a molecule made from the “death
cap” mushroom and is a known potent inhibitor RNA
polymerase.
• One single mushroom could very easily lead to a fast
death in 10 days.
• The mechanism of action is that alpha amanitin inhibits
RNA polymerase –II at both the initiation and
elongation states of transcription.
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25. Question-1
A promoter site on DNA :
a) Transcribes repressor
b) Initiates transcription
c) Codes for RNA Polymerase
d) Regulates termination
e) Translates specific proteins
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27. Question 2
The removal of introns and subsequent self-splicing of adjacent exons
occurs in some portions of primary ribosomal RNA transcripts. The
splicing of messenger RNA precursor is :
a) RNA catalyzed in the absence of proteins
b) Self-splicing
c) Carried out by spliceosomes
d) Controlled by RNA polymerase
e) Regulated by RNA helicase
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29. Question 3
In bacterial RNA synthesis, the function of factor Rho is to :
a) Increase the rate of RNA synthesis
b) Allow accurate initiation of transcription
c) Participate in termination of transcription
d) Allow the binding of RNA polymerase to the promoter
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30. Answer
c) Participate in termination of transcription
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31. Question 4
Two couples present to the emergency room with severe nausea,
vomiting, and diarrhea. One of the patients admits that she served a
salad at a dinner party to which she had added a few mushrooms. With
this information, it is likely that their symptoms are as a result of
inhibition of:
a) RNA Polymerase II
b) RNA Polymerase I
c) RNA splicing
d) RNA Polyadenylation
e) RNA Polymerase III
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33. Question 5
A second-year student isolates nucleic acids from the cell, and finds
that some of the nucleic acids are pseudouridine and ribothymidine.
Which type of nucleic acid might have been isolated?
a) t RNA
b) rRNA
c) m RNA
d) Sn RNA
e) Mi RNA
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35. Question 6
A 35-year-old female develops fever, night sweats, weight loss, and a
blood-tinged cough. An infectious disease doctor prescribed
Rifampicin. Which of the following enzymes is inhibited by Rifampicin?
a) DNA-dependent DNA polymerase
b) DNA-dependent RNA polymerase
c) RNA-dependent DNA polymerase
d) RNA-dependent RNA polymerase
e) Reverse transcriptase
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37. Question 6
Actinomycin D, is an inhibitor of transcription, which acts as by
inhibiting-
a) β- subunit of prokaryotic RNA polymerase
b) Movement of RNA polymerase along the DNA template
c) Sigma subunit of RNA polymerase
d) Prokaryotic Topoisomerase II
e) Prokaryotic helicase
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38. Answer
b) Movement of RNA polymerase along the DNA template
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39. Question 7
The initial RNA produced during the translation of DNA to RNA, which
contains both the coding exons and the non-coding introns, is known as
which of the following?
a) Amino acyl transfer RNA
b) m RNA
c) Ribosomal RNA
d) Heterogeneous nuclear RNA
e) Small nuclear RNA
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41. Question 8
Which of the following processes is not involved in the post
transcriptional processing of t-RNA?
A) Attachment of poly A tail
B) Trimming
C) Splicing
D) Attachment of CCA arm
E) Base modification
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44. Genetic Code
Genetic code is a dictionary that corresponds with sequence of
nucleotides and sequence of Amino Acids.
Words in dictionary are in the form of codons
Each codon is a triplet of nucleotides
64 codons in total and three out of these are Non Sense
codons.
61 codons for 20 amino acids
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46. Genetic Code-Characteristics
Specificity- Genetic code is specific (Unambiguous)
A specific codon always codes for the same amino acid.
e.g., UUU codes for Phenyl Alanine, it can not code for any other
amino acid.
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47. Genetic Code-Universal
Universal- In all living organism Genetic code is the same.
The exception to universality is found in mitochondrial codons
where AUA codes for methionine and UGA for tryptophan,
instead of isoleucine and termination codon respectively of
cytoplasmic protein synthesizing machinery.
AGA and AGG code for Arginine in cytoplasm but in
mitochondria they are termination codons.
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48. Genetic Code-Redundant
Redundant- Genetic code is
Redundant, also called
Degenerate.
Although each codon
corresponds to a single amino
acid, but a single amino acid
can have multiple codons.
Except Tryptophan and
Methionine each amino acid
has multiple codons.
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49. Genetic Code- Non-Overlapping and Non-
Punctuated
All codons are independent sets of 3 bases.
There is no overlapping ,
Codon is read from a fixed starting point as a continuous
sequence of bases, taken three at a time.
The starting point is extremely important, and this is called
Reading frame.
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50. Non-Sense Codons
There are 3 codons out of 64 in
genetic code which do not encode
for any Amino Acid.
These are called termination
codons or stop codons or
nonsense codons. The stop
codons are UAA, UAG, and
UGA. They encode no amino
acid. The ribosome pauses and
falls off the mRNA.
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51. Initiator codon
AUG is the initiator codon in majority of proteins-
In a few cases GUG may be the initiator codon
Methionine is the only amino acid specified by just one codon,
AUG.
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52. Wobbling phenomenon
The rules of base pairing are relaxed
at the third position, so that a base can
pair with more than one
complementary base.
Some tRNA anticodons
have Inosine at the third position.
Inosine can pair with U, C, or A. This
means that we don't need 61 different
tRNA molecules, only half as many
are required.
52
t RNA (first
base)
m RNA
(Third base)
Base pairing
C G Traditional
A U Traditional
U A Traditional
U G Nontraditio
nal
G C Traditional
G U Nontraditio
nal
I U Nontraditio
nal
I C Nontraditio
nal
I A Nontraditio
nal
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53. Question 9
The following are all characteristics of genetic code except:
a. Universal
b. Degenerate
c. Non-overlapping
d. Ambiguous
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57. Question 10
Which statement about genetic code is most accurate?
a) Information is stored as sets of dinucleotide repeats called codons
b) The code is degenerate (more than one codon may exist for a single
amino acid)
c) Information is stored as sets of trinucleotide repeats called codons.
d) There are 64 codons, all of which code for amino acids.
e) The sequence of the codons that make up a gene exhibits an exact
linear correspondence to the sequence of amino acids in the
translated protein.
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58. Answer
e) The sequence of the codons that make up a gene exhibits an exact
linear correspondence to the sequence of amino acids in the translated
protein.
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60. Translation
• The pathway of protein synthesis is called Translation
because the ‘language’ of the nucleotide sequence on the
mRNA is translated into the language of the amino acid
sequence.
• The mRNA is translated from its 5’end to its 3’end , producing
a protein synthesized from its amino terminal end to its
carboxyl terminal end.
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61. Components required for Translation
• Amino acids
• Transfer RNA
• Messenger RNA
• Aminoacyl t RNA synthetase
• Functionally competent ribosomes
• Protein factors
• ATP and GTP as a source of energy
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62. Steps of Protein Synthesis
The process of protein
synthesis is divided into 3
stages-
- Initiation
- Elongation
- Termination
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64. The small subunit/IF3 complex binds to the mRNA.
Specifically, it binds to the sequence AGGAGG, known as the
Shine-Delgarno sequence, which is found in all prokaryotic
mRNAs.
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65. Meanwhile, the fmet tRNA binds to Initiation Factor 2 (IF2), which
promotes binding of the tRNA to the start codon.
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66. The small subunit/IF3 complex scans along the mRNA until it
encounters the start codon. The tRNA/IF2 complex also binds
to the start codon. This complex of the small ribosomal
subunit, IF3, initiator tRNA, and IF2 is called the initiation
complex.
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67. At this point, the large ribosomal subunit joins in. A molecule of
GTP is hydrolyzed, and the initiation factors are released. The
ribosomal complex is now ready for protein synthesis.
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68. When the ribosome is assembled, two tRNA binding sites are created;
these are designated 'P' and 'A' (P stands for peptidyl, A stands for
amino acyl). The initiator tRNA is in the P site, and the A site will be
filled by the tRNA with the anticodon that is complementary to the
codon next to the start. (In this case, it is the tRNA that binds proline.)
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69. When the second tRNA base pairs with the appropriate codon in the mRNA,
an enzyme called peptidyl transferase catalyzes the formation of a peptide
bond between the two amino acids present (while breaking the bond
between fmet and its tRNA).This activity is intrinsic to the 23S r RNA found in
the large subunit. Since the r RNA catalyzes this process , it is referred to as
the Ribozyme
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70. Elongation
At this point, the whole ribosome shifts over one codon. This shift
requires several elongation factors (not shown) and energy from the
hydrolysis of GTP. The result of the shift is that the uncharged tRNA that
was in the P site is ejected, and the tRNA that was in the A site is now in
the P site. The A site is free to accept the tRNA molecule with the
appropriate anticodon for the next codon in the mRNA.
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71. The next tRNA base pairs with the next codon, and peptidyl transferase
catalyzes the formation of a peptide bond between the new amino acid
and the growing peptide chain.
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72. Termination
When a termination codon enters the A site, translation halts. This is because there
is no tRNA with an anti codon that is complementary to any of the stop codons.
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73. Inhibitors of protein synthesis
• The tetracyclines (tetracycline, doxycycline, demeclocycline,
minocycline, etc.) block bacterial translation by binding reversibly to
the 30S subunit and distorting it in such a way that the anticodons of
the charged tRNAs cannot align properly with the codons of the
mRNA.
• Puromycin structurally binds to the amino acyl t RNA and becomes
incorporated into the growing peptide chain thus causing inhibition of
the further elongation.
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74. Inhibitors of protein synthesis
• Chloramphenicol inhibits prokaryotic peptidyl transferase
• Clindamycin and Erythromycin bind irreversibly to a site on
the 50 s subunit of the bacterial ribosome thus inhibit
translocation.
• Diphtheria toxin inactivates the eukaryotic elongation
factors thus prevent translocation.
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75. Post Translational Modifications
The newly synthesized protein is modified to become functionally
active. The various post translational modifications are as follows-
-Trimming
-Covalent Alterations
a)Phosphorylation
b) Glycosylation
c) Hydroxylation
d) Gamma carboxylation
e) Isoprenylation
-Protein degradation 7512-Jan-21 Our Biochemistry- Namrata Chhabra
76. Post Translational Modifications
Trimming removes excess amino acids.
Phosphorylation may activate or inactivate the protein
Glycosylation targets a protein to become a part of the plasma
membrane or lysosomes or be secreted out of the cell
Hydroxylation such as seen in collagen is required for acquiring the
three-dimensional structure and for imparting strength
Defective proteins or destined for turn over are marked for destruction
by attachment of a Ubiquitin protein. Proteins marked in this way are
degraded by a cellular component known as the Proteasome.
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77. Question 11
The initiation of translation in eukaryotes requires which of the
following:
a. Initiation factor (IF-2)
b. Elongation factor (EF)-2
c. A 40-S ribosomal subunit
d. Methionyl-tRNA (f Met).
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78. Answer
c) A 40-S ribosomal subunit
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79. Question 12
Which of the following statements about prokaryotic translation is
incorrect?
a. Transcription and translation are simultaneous
b. Initiation takes place with the help of Methionyl-tRNA (f Met)
c. 20 S and 60 S subunits together form a ribosome of 80 S
d. Chloramphenicol inhibits prokaryotic translation.
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80. Answer
c. 20 S and 60 S subunits together form a ribosome of 80 S
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81. Question 13
Which of the following components is required in prokaryotic protein
synthesis?
a. Aminoacyl t RNA synthetase
b. Helicase
c. Topoisomerase
d. Primase.
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83. Question 14
A 34-year-old female develops a nonproductive cough and a low-grade
fever. The attending physician suspects Mycoplasma pneumonia and
starts empirically with Erythromycin.
Which of the following describes the mechanism of action of
Erythromycin?
a) Inhibits the 50S ribosomal subunit.
b) Inhibits the initiation factor- 1(IF-1).
c) Binds to shine Dalgarno sequence.
d) Inhibits the incoming aminoacyl tRNA.
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84. Answer
a) Inhibits the 50S ribosomal subunit
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85. Question 15
A -4-year-old girl has been brought to the Pediatric OPD with fever and
cough that sounds like a “whoop”. The pediatrician learns that the child
has not been properly immunized and has yet to receive Pertussis
vaccination.
The mechanism by which the pertussis toxin causes cell death is
through the inhibition of:
a. Translocase
b. Peptidyl transferase
c. Elongation factor (EF)-2
d. Aminoacyl t-RNA synthetase.
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87. Question 16
An 18-year-old girl has been advised to start with Tetracycline for the
treatment for her acne. Which of the following statements best
describes the mechanism of action of Tetracycline?
Tetracycline:
a. binds reversibly to the 30S subunit and distorts it.
b. inhibits prokaryotic Peptidyl Transferase
c. inactivates the prokaryotic elongation factors
d. structurally binds to the aminoacyl t RNA.
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88. Answer
a. binds reversibly to the 30S subunit and distorts it.
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89. Question 17
A 34-year-old has reported to the Medical OPD with a high -grade fever,
dry cough, headache, loss of appetite, and pain abdomen lasting from
the past seven days. She has been diagnosed with typhoid fever, for
which she has been started with Chloramphenicol.
The drug acts by inhibiting prokaryotic :
a. Translocase
b. Peptidyl transferase
c. Initiation factor (IF)-2
d. Aminoacyl t-RNA synthetase.
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91. Question 18
Immunoglobulins, hemoglobin, and collagen are modified post-
translationally by the process of:
a) Hydroxylation
b) Subunit aggregation
c) Methylation
d) Trimming.
e) Carboxylation
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94. INTRODUCTION
● A mutation is a permanent change in the
nucleotide sequence of a gene.
● Mutations may be either gross, so that
large areas of chromosome are changed,
● or may be subtle with a change in one or a
few nucleotides.
Mutations
Large scale
Point
mutations
94
101. Mutagens
● Chemicals
o Nitroso compounds
o Hydroxylamine NH2OH
o Base analogs
o Simple chemicals (e.g. acids)
○ Alkylating & methylating agents (e.g. N-
ethyl-N-nitrosourea (ENU)
101
102. Mutagens
● Chemicals
o Polycyclic aromatic hydrocarbons e.g. benzopyrenes
o DNA intercalating agents (e.g. ethidium bromide)
o DNA cross linker (e.g. platinum)
o Oxidative damage caused by oxygen(O)radicals
102
103. Mutagens
❖ Radiations
● Ultraviolet radiation (non-ionizing radiation) - excites electrons to a higher
energy level. DNA absorbs ultraviolet light. Two nucleotide bases in DNA -
cytosine and thymine-are most vulnerable to excitation that can change base-
pairing properties. UV light can induce adjacent thymine bases in a DNA strand
to pair with each other, as a bulky dimer.
● Ionizing radiation
103
107. Insertional
mutagenesis
● Insertions in the coding
region of a gene may
alter splicing of the
mRNA (splice site
mutation), or
● cause a shift in the
reading frame (frame
shift), both of which can
significantly alter the
gene product.
107
108. A) Point mutations
iii) Deletions remove one
nucleotide from the DNA.
Like insertions, these
mutations can alter the
reading frame of the gene.
108
109. B) Large-scale mutations
B) Large-scale mutations in chromosomal structure, including:
Amplifications (or gene duplications) leading to multiple copies of all
chromosomal regions, increasing the dosage of the genes located within
them.
109
111. B) Large-scale mutations
c) Chromosomal Mutations:
○ Chromosomal translocations: interchange of genetic parts from
nonhomologous chromosomes.
○ Interstitial deletions: an intra-chromosomal deletion that removes a
segment of DNA from a single chromosome, thereby apposing
previously distant genes.
○ Chromosomal inversions: reversing the orientation of a
chromosomal segment.
111
112. Effects of point mutations
Single-base changes in the mRNA molecules may have one of several effects
when translated into protein:
1. Silent mutations-There may be no detectable effect because of the
degeneracy of the code.
2. This would be more likely if the changed base in the mRNA molecule
were to be at the third nucleotide of a codon.
112
113. Effects of point mutations
(2) A missense effect will occur when a different amino acid is incorporated
at the corresponding site in the protein molecule. This mistaken amino
acid—or missense, depending upon its location in the specific protein—
might be acceptable, partially acceptable, or unacceptable to the function
of that protein molecule.
Most single-base changes would result in the replacement of one amino acid
by another with rather similar functional groups. This is an effective
mechanism to avoid drastic change in the physical properties of a protein
molecule.
113
114. a) Acceptable Missense mutations
● The sequencing of a large number of hemoglobin mRNAs and genes from many
individuals has shown that the codon for valine at position 67 of the chain of
hemoglobin is not identical in all persons who possess a normally functional chain of
hemoglobin.
● The codon changes by point mutation from GUU (of valine) to GAU of Aspartic acid
in Hb Bristol.
● Similarly in Hb Sydney the codon changes from GUU to GCU for Alanine.
● Both Hb Bristol and Hb Sydney are normal Hb variants with normal oxygen carrying
capacity.
● Thus these are acceptable mutations.
114
115. Partially acceptable Missense mutations
● Clearly, this missense mutation hinders normal function and
results in sickle cell anemia when the mutant gene is present in
the homozygous state.
● The glutamate-to-valine change may be considered to be
partially acceptable because hemoglobin S does bind and
release oxygen, although abnormally.
115
116. c) Unacceptable Missense Mutations
● The hemoglobin M mutations generate molecules that allow the Fe2+ of the heme
moiety to be oxidized to Fe3+, producing methemoglobin.
● Here the single nucleotide change alters the properties of a protein to such an extent
that it becomes non- functional.
● Hb M results from histidine to tyrosine substitution.
● Distal Histidine of alpha chain of Globin is replaced by Tyrosine.
● The codon CAU is changed to UAU with the resultant incorporation of Tyrosine and
formation of MetHb.
● Met hemoglobin cannot transport oxygen.
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117. (3) A nonsense mutation
A nonsense codon may appear that would then result in the premature
termination of a peptide chain and the production of only a fragment of the
intended protein molecule.
The probability is high that a prematurely terminated protein molecule or
peptide fragment will not function in its assigned role.
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118. (3) A nonsense mutation
● The codon UAC for Tyrosine may be mutated to UAA or UAG, both are stop
codons. Beta Thalassemia is an example of nonsense mutation.
● In certain conditions as a result of mutational event the stop codon may be
changed to normal codon (UAA to CAA) .
● This results in the elongation of protein to produce “Run on polypeptides”.
The resultant protein is a functionally abnormal protein.
118
119. Frameshift Mutations
● A frame shift mutation is a mutation caused by inserts or deletes of a number of
nucleotides from a DNA sequence.
● Due to the triplet nature of gene expression by codons, the insertion or deletion
can disrupt the reading frame, or the grouping of the codons, resulting in a
completely different translation from the original.
● The earlier in the sequence the deletion or insertion occurs, the more altered
the protein produced is.
119
120. Triplet deletion
A triplet deletion removes exactly
one amino acid from the
polypeptide ,the most common
mutation in cystic fibrosis is Delta
F508 (i.e. deletion of amino acid
number 508 (a phenylalanine, F).
120
121. Trinucleotide expansion
● The commonest inherited cause of mental retardation is a
syndrome originally known as Martin-Bell syndrome.
● Patients are most usually male, have a characteristic
elongated face and numerous other abnormalities
including greatly enlarged testes.
● In 1969 the name of the syndrome was changed to the
fragile X syndrome.
121
122. Trinucleotide expansion
● The mutation was tracked down to a trinucleotide expansion in
the gene now named FMR1 (Fragile site with Mental
Retardation).
● A number of diseases have now been ascribed to trinucleotide
expansions.
● These include Huntington's disease and Myotonic dystrophy.
122
123. Gene deletions
● Alpha Thalassemia is an
example of Gene
deletion.
● The clinical
manifestations are as per
the number of genes
deleted.
123
124. Consequences of Mutations
Harmful mutations
● Changes in DNA caused by mutation can cause errors in protein
sequence, creating partially or completely non-functional proteins.
● To function correctly, each cell depends on thousands of proteins to
function in the right places at the right times.
● When a mutation alters a protein that plays a critical role in the body, a
medical condition can result.
● A condition caused by mutations in one or more genes is called a genetic
disorder.
124
125. Consequences of Mutations
● If a mutation is present in a germ cell, it can give rise to
offspring that carries the mutation in all of its cells.
● This is the case in hereditary diseases.
● On the other hand, a mutation can occur in a somatic cell of an
organism.
● Such mutations will be present in all descendants of this cell,
and certain mutations can cause the cell to become malignant,
and thus cause cancer.
125
126. Consequences of Mutations
Beneficial mutations
● A very small percentage of all mutations actually have a positive effect.
● These mutations lead to new versions of proteins that help an organism
and its future generations better adapt to changes in their environment.
● For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32)
confers HIV resistance to homozygotes and delays AIDS onset in
heterozygotes.
● The CCR5 mutation is more common in those of European descent.
126
127. Question 19
Triple repeat sequence disease occurs in:
a) Alzheimer’s disease
b) Cystic fibrosis
c) Ataxia telangiectasia
d) Huntington’s chorea
12712-Jan-21 Our Biochemistry- Namrata Chhabra
129. Question 20
Which of the following changes in mRNA (resulting form point
mutation) would result in the synthesis of a protein identical to the
normal protein?
a. UCA – UAA
b. UCA- CCA
c. UCA- UCU
d. UCA- ACA
12912-Jan-21 Our Biochemistry- Namrata Chhabra
131. Question 21
A-58-year-old male has recently been diagnosed with
hemochromatosis. He presents with bronze discoloration of the skin
and is found to have elevated plasma glucose and ferritin levels. The
physician finds that he is carrying a mutation where tyrosine is
substituted for Cysteine of the HFE gene. This disease results from
which of the following mutations?
a. Silent
b. Nonsense
c. Missense
d. Frameshift.
13112-Jan-21 Our Biochemistry- Namrata Chhabra