Molecular Biology and Genomics Practice Questions

Q: Which of the following statements about nucleotide excision repair is FALSE?

Only the damaged nucleotides are removed.. **Explanation:** **1. Why Option D is the Correct (False) Statement:** In Nucleotide Excision Repair (NER), the repair mechanism does not just remove the single damaged nucleotide. Instead, an **exinuclease** (excision endonuclease) makes two incisions on the damaged strand—one on the 5' side and one on the 3' side of the lesion. This results in the removal of an **oligonucleotide fragment** (a short stretch of about 12–13 nucleotides in prokaryotes and 24–32 in eukaryotes). Therefore, the statement that "only the damaged nucleotides are removed" is incorrect. **2. Analysis of Incorrect Options:** * **Option A:** NER is highly specific for bulky lesions on a **single strand**. The complementary undamaged strand serves as a template for DNA polymerase to fill the gap. * **Option B:** This is the classic function of NER. It identifies and repairs bulky, helix-distorting lesions, most notably **pyrimidine dimers (thymine dimers)** caused by UV radiation. * **Option C:** After the oligonucleotide fragment is removed, **DNA Polymerase (δ/ε)** fills the gap using the opposite strand as a template, and **DNA Ligase** seals the final phosphodiester bond. **3. Clinical Pearls & High-Yield Facts:** * **Xeroderma Pigmentosum (XP):** A classic NEET-PG topic. It is caused by a genetic deficiency in NER proteins (e.g., XP-A to XP-G). Patients present with extreme photosensitivity and a 1000-fold increased risk of skin cancers. * **Cockayne Syndrome:** Another disorder linked to a subtype of NER (Transcription-Coupled Repair), characterized by growth retardation and neurological degeneration. * **Contrast with BER:** Base Excision Repair (BER) uses **glycosylases** to remove a single "wrong" base, whereas NER removes a "patch" of nucleotides.

Q: Which one of the following disorders is due to maternal disomy of chromosome 15?

Prader-Willi syndrome. This question tests your knowledge of **Genomic Imprinting** and **Uniparental Disomy (UPD)** involving Chromosome 15 (region 15q11-q13). ### **Explanation of the Correct Answer** **Prader-Willi Syndrome (PWS)** occurs when there is a loss of function of the **paternally** derived genes on chromosome 15. While the most common cause (70%) is a microdeletion on the paternal chromosome, approximately 25–30% of cases are caused by **Maternal Uniparental Disomy (UPD)**. In maternal UPD, the offspring inherits two copies of chromosome 15 from the mother and none from the father. Since the maternal genes in this region are normally silenced (imprinted), the absence of the active paternal contribution leads to the disease. ### **Analysis of Incorrect Options** * **B. Angelman Syndrome:** This is the "sister" condition caused by the loss of the **maternally** inherited *UBE3A* gene. It is most commonly due to maternal deletion or **Paternal UPD** (inheriting two paternal copies where the gene is silenced). * **C. Hydatidiform Mole:** A complete mole is an example of **androgenesis**, where all 46 chromosomes are of paternal origin (usually due to fertilization of an empty egg by two sperm or one sperm that duplicates). * **D. Klinefelter’s Syndrome:** This is a numerical chromosomal aberration (47, XXY) resulting from nondisjunction, not imprinting or uniparental disomy. ### **High-Yield Clinical Pearls for NEET-PG** * **PWS Clinical Triad:** Neonatal hypotonia ("floppy baby"), hyperphagia leading to early-onset obesity, and hypogonadism. * **Angelman Clinical Triad:** "Happy Puppet" posture (inappropriate laughter), seizures, and ataxia/jerky movements. * **Mnemonic:** **P**rader-Willi = **P**aternal deletion / **M**aternal Disomy. **A**ngelman = **M**aternal deletion / **P**aternal Disomy. (Remember: **P**ader-Willi is **P**ops' gene missing).

Q: Which of the following activities is associated with 5' to 3' exonuclease activity?

Repair of damaged DNA. **Explanation:** In prokaryotes, **DNA Polymerase I** is unique because it possesses three distinct enzymatic activities: 5'→3' polymerase, 3'→5' exonuclease, and **5'→3' exonuclease**. **1. Why "Repair of damaged DNA" is correct:** The 5'→3' exonuclease activity is specifically designed to remove nucleotides in the same direction as DNA synthesis. This is essential for: * **Primer Removal:** It excises RNA primers during lagging strand synthesis. * **DNA Repair (Nick Translation):** It removes damaged DNA segments or mismatched bases ahead of the polymerase, allowing DNA Polymerase I to simultaneously fill the gap with correct nucleotides. This dual action is vital for Base Excision Repair (BER) and Nucleotide Excision Repair (NER). **2. Why other options are incorrect:** * **A. Proofreading:** This is the function of **3'→5' exonuclease activity**. It allows the enzyme to "backspace" and remove an incorrectly incorporated base at the 3' end. * **C. DNA synthesis:** This refers to the **5'→3' polymerase activity**, which adds dNTPs to the growing chain. * **D. DNA polymerase:** This is a general term for the enzyme. While it *has* the activity, the question asks which specific *biological process* is associated with the 5'→3' exonuclease function. **High-Yield Clinical Pearls for NEET-PG:** * **DNA Polymerase III:** The primary enzyme for elongation; it lacks 5'→3' exonuclease activity. * **Klenow Fragment:** A proteolytic fragment of DNA Pol I that retains polymerase and 3'→5' exonuclease (proofreading) but **lacks** 5'→3' exonuclease activity. * **Xeroderma Pigmentosum:** A clinical condition caused by a defect in Nucleotide Excision Repair (NER), highlighting the importance of DNA repair mechanisms.

Q: Enzymatic activity of RNA is involved in all of the following EXCEPT?

RNA-Aptamer binding to cognate small molecules. ### Explanation The question tests the distinction between **Ribozymes** (catalytic RNA) and **RNA Aptamers** (binding RNA). **1. Why Option A is the Correct Answer:** An **RNA Aptamer** is a short, single-stranded nucleic acid molecule that folds into a specific 3D structure to bind to a target molecule (like a protein or small metabolite) with high affinity and specificity. This is a **binding/recognition** function, similar to an antibody-antigen interaction, and does **not** involve the chemical transformation of a substrate. Therefore, it lacks enzymatic (catalytic) activity. **2. Analysis of Incorrect Options (Catalytic Functions):** * **B. Cleavage of nucleic acids:** Ribozymes like **RNase P** (involved in tRNA processing) and **Hammerhead ribozymes** catalyze the phosphodiester bond cleavage of RNA. * **C. Peptide bond formation:** The **23S rRNA** (in prokaryotes) or **28S rRNA** (in eukaryotes) of the large ribosomal subunit acts as a **Peptidyl transferase**. It catalyzes the formation of peptide bonds during translation. This is a classic example of a ribozyme. * **D. RNA splicing:** **Small nuclear RNAs (snRNAs)** within the spliceosome catalyze the transesterification reactions required to remove introns and join exons. **3. High-Yield Facts for NEET-PG:** * **Ribozyme Definition:** RNA molecules that accelerate chemical reactions without being consumed. * **Thomas Cech & Sidney Altman:** Awarded the Nobel Prize for discovering the catalytic properties of RNA. * **Clinical Pearl:** **Macugen (Pegaptanib)** is an FDA-approved **RNA Aptamer** used in the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD) by binding to VEGF. * **Riboswitch:** A regulatory segment of an mRNA molecule that binds a small molecule (aptamer domain), resulting in a change in production of the proteins encoded by the mRNA.

Q: A sample of human DNA is subjected to increasing temperature until a major portion of the sample melts. A small portion of the DNA requires even higher temperature for melting compared to the rest of the sample. This suggests that the higher melting temperature portion has a higher content of which of the following nucleotide pairs?

Cytosine and Guanine. ### Explanation **1. Why Cytosine and Guanine (C-G) is Correct:** The stability of the DNA double helix is primarily determined by the hydrogen bonds between complementary base pairs. * **Guanine (G) and Cytosine (C)** are held together by **three hydrogen bonds**. * **Adenine (A) and Thymine (T)** are held together by only **two hydrogen bonds**. The **Melting Temperature ($T_m$)** is the temperature at which 50% of double-stranded DNA denatures into single strands. Because C-G pairs have a higher density of hydrogen bonds, they require more thermal energy to break. Therefore, DNA sequences with a high **G-C content** exhibit a higher $T_m$ compared to A-T rich regions. **2. Why Other Options are Incorrect:** * **Option D (Adenine and Thymine):** These pairs only have two hydrogen bonds. A high A-T content actually *lowers* the melting temperature. For example, the TATA box in promoter regions is A-T rich specifically to allow easier unwinding of DNA for transcription. * **Options A & C (A-G and C-T):** These options pair a purine with a purine or a pyrimidine with a pyrimidine. In a normal B-DNA structure, base pairing occurs between a purine and a pyrimidine (A with T, G with C). These combinations do not represent standard complementary base pairs in the double helix. **3. High-Yield Clinical Pearls for NEET-PG:** * **Hyperchromicity:** When DNA melts (denatures), its absorbance of UV light at **260 nm** increases. This is known as the hyperchromic effect. * **Factors increasing $T_m$:** High G-C content and high salt concentration (cations like $Na^+$ neutralize the negatively charged phosphate backbone, stabilizing the helix). * **Factors decreasing $T_m$:** High A-T content, formamide, and urea (which disrupt hydrogen bonds). * **TATA Box:** Found in promoters; its high A-T content facilitates the "melting" required for RNA polymerase to initiate transcription.

Q: What is the primary purpose of gene therapy?

Replacement of an abnormal gene with a normal gene.. **Explanation:** **1. Why Option A is Correct:** Gene therapy is a therapeutic technique that aims to treat or prevent diseases by modifying the expression of a person’s genes. The primary mechanism involves the **introduction of a functional (normal) copy of a gene** into a patient’s cells to compensate for a defective or missing gene. By replacing or supplementing the abnormal gene, the cell can produce the necessary functional protein, thereby correcting the underlying biochemical defect of the disease. **2. Why Other Options are Incorrect:** * **Option B:** This is counter-intuitive; introducing an abnormal gene would induce disease rather than treat it. * **Option C:** While "gene silencing" or "knockout" (using CRISPR/Cas9 or RNA interference) is a *subset* of gene therapy used for dominant-negative mutations, the **primary and classical definition** remains the restoration of function via a normal gene. * **Option D:** Viral genes are used as **vectors** (delivery vehicles) to carry the therapeutic human gene into the host cell, but the goal is not the introduction of the viral gene itself. **3. NEET-PG High-Yield Pearls:** * **First Gene Therapy:** Performed in 1990 for **Adenosine Deaminase (ADA) deficiency** (a type of SCID). * **Vectors:** Commonly use **Retroviruses** (integrate into the genome) or **Adenoviruses** (remain episomal). * **Ex-vivo vs. In-vivo:** Ex-vivo involves modifying cells outside the body (e.g., bone marrow) and re-injecting them; In-vivo involves direct delivery into the patient (e.g., subretinal injection for Leber Congenital Amaurosis). * **Germline vs. Somatic:** Current clinical gene therapy is strictly **somatic**; germline therapy (affecting offspring) is ethically prohibited in humans.

Q: DNA Gyrase is:

Prokaryotic DNA Topoisomerase II. ### Explanation **DNA Gyrase** is a specialized enzyme found in **prokaryotes** that belongs to the **Type II Topoisomerase** family. Its primary function is to introduce **negative supercoils** into DNA, which helps relieve the positive superhelical tension that builds up ahead of the replication fork. Unlike Type I topoisomerases, Type II enzymes (like DNA Gyrase) catalyze the breakage of both strands of the DNA double helix and require ATP for their activity. #### Analysis of Options: * **Option D (Correct):** DNA Gyrase is the bacterial version of Topoisomerase II. It is unique because it is the only enzyme capable of introducing negative supercoils, which is essential for compacting the bacterial chromosome and facilitating replication. * **Option A:** Eukaryotic Topoisomerase I relaxes supercoils by cutting a single strand of DNA and does not require ATP. * **Option B:** Prokaryotic Topoisomerase III is a Type I topoisomerase involved primarily in recombination and resolving "knots" in DNA. * **Option C:** Prokaryotic Topoisomerase I (also known as Omega protein) relaxes negative supercoils but cannot introduce them. #### Clinical Pearls for NEET-PG: * **Pharmacological Target:** DNA Gyrase is the primary target of **Quinolones and Fluoroquinolones** (e.g., Ciprofloxacin, Nalidixic acid). These drugs inhibit the A-subunit of the enzyme, leading to bacterial cell death. * **Subunit Structure:** It is a tetramer composed of two **GyrA** subunits (involved in DNA breakage/rejoining) and two **GyrB** subunits (possessing ATPase activity). * **Eukaryotic Counterpart:** Humans possess Topoisomerase II, but it lacks the ability to introduce negative supercoils; it only relaxes them. This structural difference allows for selective toxicity of antibiotics.

Q: What does the amber codon refer to?

Stop codon. **Explanation:** The correct answer is **B. Stop codon**. In molecular biology, translation termination is signaled by specific nucleotide triplets called **Stop codons** (or nonsense codons). There are three stop codons in the universal genetic code: 1. **UAG (Amber)** 2. **UGA (Opal)** 3. **UAA (Ochre)** These codons do not code for any amino acid. Instead, they are recognized by release factors that trigger the hydrolysis of the ester bond between the tRNA and the polypeptide chain, effectively terminating protein synthesis. The name "Amber" was a whimsical designation given by researchers (specifically Caltech's Richard Epstein and Charles Steinberg) based on the German translation of the last name of their colleague, Harris Bernstein. **Analysis of Incorrect Options:** * **A. Mutant codon:** While a mutation can create a stop codon (known as a **nonsense mutation**), the term "Amber" specifically refers to the UAG sequence itself, not the process of mutation. * **C. Initiating codon:** The universal initiation codon is **AUG**, which codes for Methionine (in eukaryotes) or N-formylmethionine (in prokaryotes). * **D. Codon for more than one amino acid:** This describes **ambiguity**. However, the genetic code is **unambiguous**, meaning one codon always codes for only one specific amino acid. **NEET-PG High-Yield Pearls:** * **Mnemonic to remember stop codons:** **U** **A**re **G**one (UAG), **U** **G**o **A**way (UGA), **U** **A**re **A**way (UAA). * **Nonsense Mutation:** A point mutation that changes an amino acid codon into a stop codon, leading to a truncated, usually non-functional protein. * **Exceptions:** In human mitochondria, UGA codes for Tryptophan rather than acting as a stop codon. * **Selenocysteine:** Known as the 21st amino acid, it is encoded by the UGA codon when a specific insertion sequence (SECIS) is present.

Q: Which of the following is NOT a characteristic of the genetic code?

Contains punctuation signals. The genetic code is the set of rules by which information encoded in genetic material is translated into proteins. Understanding its properties is fundamental for NEET-PG biochemistry. ### **Explanation of the Correct Answer** **C. Contains punctuation signals:** This is the correct answer because the genetic code is **commaless**. Once translation begins at the start codon (AUG), the mRNA is read continuously, three nucleotides at a time, without skipping any bases or using "punctuation" marks between codons. There are no spacers between the triplets. While there are "Stop" codons (UAA, UAG, UGA) that signal the end of translation, they do not act as internal punctuation between individual amino acids. ### **Analysis of Incorrect Options** * **A. Degenerate:** This is a true characteristic. Most amino acids are coded by more than one codon (e.g., Leucine has six). This provides a buffer against mutations (often at the 3rd "wobble" position). * **B. Universal:** The code is consistent across almost all organisms, from bacteria to humans. *Exception:* Mitochondrial DNA (e.g., UGA codes for Tryptophan instead of Stop). * **D. Non-overlapping:** Each nucleotide is part of only one codon. In a sequence ABCDEF, the codons are ABC and DEF, never BCD. ### **High-Yield Clinical Pearls for NEET-PG** * **Wobble Hypothesis:** Proposed by Francis Crick; explains why the 3rd base of a codon can have non-traditional pairing, allowing one tRNA to recognize multiple codons. * **Initiation Codon:** **AUG** (codes for Methionine in eukaryotes and N-formylmethionine in prokaryotes). * **Nonsense Mutations:** Occur when a point mutation changes an amino acid codon into a **Stop codon** (UAA, UAG, UGA), leading to premature protein termination. * **Frameshift Mutations:** Result from the insertion or deletion of nucleotides (not in multiples of three), which alters the entire reading frame because the code is commaless and non-overlapping.

Question 1

What is true about ribosomes?

Accepted Answer

They are conserved in nature.

Answer

Their role is to bring tRNA and mRNA together.

Answer

DNA forms RNA, and proteins are formed from RNA.

Answer

They are always free.

Question 2

Which of the following statements about nucleotide excision repair is FALSE?

Accepted Answer

Only the damaged nucleotides are removed.

Answer

Removal of damaged bases occurs only on one strand of the DNA.

Answer

It removes thymine dimers generated by UV light.

Answer

Requires ligase and polymerase.

Question 3

Which one of the following disorders is due to maternal disomy of chromosome 15?

Accepted Answer

Prader-Willi syndrome

Answer

Angelman syndrome

Answer

Hydatidiform mole

Answer

Klinefelter's syndrome

Question 4

Which of the following activities is associated with 5' to 3' exonuclease activity?

Accepted Answer

Repair of damaged DNA

Answer

Proofreading

Answer

DNA synthesis

Answer

DNA polymerase

Question 5

Enzymatic activity of RNA is involved in all of the following EXCEPT?

Accepted Answer

RNA-Aptamer binding to cognate small molecules

Answer

Cleavage of nucleic acids

Answer

Peptide bond formation

Answer

RNA splicing

Question 6

A sample of human DNA is subjected to increasing temperature until a major portion of the sample melts. A small portion of the DNA requires even higher temperature for melting compared to the rest of the sample. This suggests that the higher melting temperature portion has a higher content of which of the following nucleotide pairs?

Accepted Answer

Cytosine and Guanine

Answer

Adenine and Guanine

Answer

Cytosine and Thymine

Answer

Adenine and Thymine

Question 7

What is the primary purpose of gene therapy?

Accepted Answer

Replacement of an abnormal gene with a normal gene.

Answer

Replacement of a normal gene with an abnormal gene.

Answer

Knockout of an abnormal gene.

Answer

Introduction of a viral gene.

Question 8

DNA Gyrase is:

Accepted Answer

Prokaryotic DNA Topoisomerase II

Answer

Eukaryotic DNA Topoisomerase I

Answer

Prokaryotic DNA Topoisomerase III

Answer

Prokaryotic DNA Topoisomerase I

Question 9

What does the amber codon refer to?

Accepted Answer

Stop codon

Answer

Mutant codon

Answer

Initiating codon

Answer

Codon for more than one amino acid

Question 10

Which of the following is NOT a characteristic of the genetic code?

Accepted Answer

Contains punctuation signals

Answer

Degenerate

Answer

Universal

Answer

Non-overlapping

Molecular Biology and Genomics — MCQs

Molecular Biology and Genomics — MCQs

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