Molecular Biology and Genomics — MCQs

Molecular Biology and Genomics Indian Medical PG Practice Questions and MCQs

Question 391: Which of the following is true about DNA polymerase in eukaryotes?

A. Components are α, β, γ, δ, ε
B. β is associated with repair (Correct Answer)
C. γ is associated with repair
D. δ is associated with synthesis of mitochondrial DNA

Explanation: In eukaryotic DNA replication, multiple specialized DNA polymerases carry out distinct functions. Understanding their specific roles is high-yield for NEET-PG. ### **Explanation of the Correct Option** **Option B is correct.** **DNA Polymerase β (Beta)** is a specialized enzyme primarily involved in **Base Excision Repair (BER)**. It lacks 3'→5' exonuclease activity (proofreading) and is responsible for filling short gaps (1–2 nucleotides) created during the repair of damaged DNA bases. ### **Analysis of Incorrect Options** * **Option A:** While α, β, γ, δ, and ε are the primary eukaryotic polymerases, this option is a simple list of components rather than a functional statement. In the context of "which is true," Option B provides a specific, accurate functional relationship. * **Option C:** This is incorrect. **DNA Polymerase γ (Gamma)** is responsible for the replication and repair of **mitochondrial DNA**, not general nuclear DNA repair. * **Option D:** This is incorrect. As stated above, mitochondrial DNA synthesis is the role of **Polymerase γ**, whereas **Polymerase δ (Delta)** is responsible for the synthesis of the **lagging strand** in nuclear DNA replication. ### **High-Yield Clinical Pearls for NEET-PG** * **Mnemonic (Eukaryotic Polymerases):** * **α (Alpha):** Contains **primase** activity; initiates replication. * **β (Beta):** **B**ase excision repair (**B**=**B**oth are 'B'). * **γ (Gamma):** **G**enerates mitochondrial DNA (**G**=**G**round/Powerhouse). * **δ (Delta):** **D**elays (Lagging strand synthesis) and has 3'→5' proofreading. * **ε (Epsilon):** **E**longates the leading strand. * **PCNA (Proliferating Cell Nuclear Antigen):** Acts as a sliding clamp for Pol δ and ε to increase processivity; it is a clinical marker for proliferating cells in pathology. * **Aphidicolin:** A specific inhibitor of eukaryotic DNA polymerases α, δ, and ε (but not β or γ).

Question 392: What is the major component of DNA?

A. Histone
B. Repressor
C. Deoxyribonucleotides (Correct Answer)
D. Inducer

Explanation: ### Explanation **Correct Answer: C. Deoxyribonucleotides** **Why it is correct:** DNA (Deoxyribonucleic acid) is a polymer made up of repeating monomeric units called **deoxyribonucleotides**. Each deoxyribonucleotide consists of three essential components: a **deoxyribose sugar**, a **phosphate group**, and a **nitrogenous base** (Adenine, Guanine, Cytosine, or Thymine). These units are linked by 3'-5' phosphodiester bonds to form the sugar-phosphate backbone, which serves as the structural blueprint of life. **Why the other options are incorrect:** * **A. Histone:** These are highly alkaline **proteins** found in eukaryotic cell nuclei. While they are essential for packaging DNA into nucleosomes (the "beads on a string" structure), they are not a component of the DNA molecule itself. * **B. Repressor:** This is a **regulatory protein** that binds to the operator region of an operon (e.g., the *lac* operon) to inhibit gene transcription. It is a functional regulator, not a structural component. * **D. Inducer:** This is a **small molecule** (like lactose or IPTG) that initiates gene expression by disabling a repressor protein. It is a chemical signal, not a part of the DNA structure. **High-Yield Clinical Pearls for NEET-PG:** * **Chargaff’s Rule:** In double-stranded DNA, the amount of A = T and G = C; therefore, the ratio of purines to pyrimidines is always 1:1. * **Nucleoside vs. Nucleotide:** Nucleoside = Sugar + Base; Nucleotide = Sugar + Base + Phosphate. * **Z-DNA:** A rare, left-handed helix seen in regions with alternating purine-pyrimidine sequences; most physiological DNA is **B-DNA** (right-handed). * **Hyperchromicity:** When DNA is denatured (melted), its UV light absorption at 260 nm increases.

Question 393: What was the first disease successfully treated with somatic gene therapy?

A. Severe Combined Immunodeficiency (SCID) (Correct Answer)
B. Phenylketonuria
C. Thalassemia
D. Cystic fibrosis

Explanation: **Explanation:** The correct answer is **Severe Combined Immunodeficiency (SCID)**. Specifically, the first successful clinical trial of somatic gene therapy occurred in **1990** at the NIH, involving a four-year-old girl named Ashanti DeSilva. She suffered from **Adenosine Deaminase (ADA) deficiency**, a form of SCID. The procedure involved extracting her T-lymphocytes, inserting a functional copy of the ADA gene using a retroviral vector, and re-infusing the corrected cells back into her body. **Why other options are incorrect:** * **Phenylketonuria (PKU):** While PKU is a classic target for metabolic research, it is primarily managed through dietary restriction of phenylalanine. Gene therapy for PKU is still in experimental/pre-clinical stages. * **Thalassemia:** Although gene therapy for β-thalassemia (using LentiGlobin) has seen recent success and FDA approval, it was not the first. The complexity of regulating hemoglobin expression made it a later milestone. * **Cystic Fibrosis:** This was one of the earliest diseases targeted for gene therapy (targeting the CFTR gene), but early trials in the 1990s faced significant hurdles regarding delivery vectors and transient expression, failing to achieve "successful" long-term clinical treatment at that time. **High-Yield Clinical Pearls for NEET-PG:** * **Vector used:** Retroviruses are commonly used for *ex vivo* gene therapy (like ADA-SCID) because they integrate the therapeutic gene into the host genome. * **ADA Deficiency:** Leads to the accumulation of **dATP**, which is toxic to T and B lymphocytes, causing profound immunodeficiency. * **Gene Therapy Types:** Somatic gene therapy (non-heritable) is the only type currently permitted in humans; Germline gene therapy (heritable) is prohibited.

Question 394: Which of the following is an antiapoptotic gene?

A. Bax
B. Bad
C. Bcl-X (Correct Answer)
D. Bim

Explanation: **Explanation:** Apoptosis (programmed cell death) is tightly regulated by the **Bcl-2 family of proteins**, which act as a molecular switch at the mitochondrial membrane. These proteins are categorized into two functional groups: **Pro-apoptotic** (promote cell death) and **Anti-apoptotic** (promote cell survival). **Why Bcl-X is correct:** **Bcl-X** (specifically the long isoform, **Bcl-X_L**) is a potent **anti-apoptotic** protein. It resides in the outer mitochondrial membrane and functions by binding to and sequestering pro-apoptotic proteins, thereby preventing the release of Cytochrome C into the cytosol and inhibiting the activation of the caspase cascade. **Why the other options are incorrect:** * **Bax and Bak:** These are the "effector" **pro-apoptotic** proteins. Upon activation, they oligomerize to form pores in the mitochondrial outer membrane (MOMP), leading to the leakage of Cytochrome C. * **Bad and Bim:** These belong to the **BH3-only subset** of **pro-apoptotic** proteins. They act as "sensors" of cellular stress and function by either activating Bax/Bak directly or by neutralizing anti-apoptotic proteins like Bcl-2 and Bcl-X. **High-Yield NEET-PG Pearls:** * **Anti-apoptotic genes:** Bcl-2, Bcl-X, Mcl-1. (Mnemonic: "Keep the cell **B**alive with **B**cl-2") * **Pro-apoptotic genes:** Bax, Bak, Bad, Bim, Bid, PUMA, NOXA. * **Follicular Lymphoma:** Associated with **t(14;18)** translocation, which leads to the overexpression of the **Bcl-2** anti-apoptotic gene, preventing cancer cells from undergoing death. * **Guardian of the Genome:** **p53** induces apoptosis by upregulating **Bax** when DNA damage is irreparable.

Question 395: RNA participates directly in all of the following except:

A. Post translational modification (Correct Answer)
B. Post transcriptional modification
C. DNA replication
D. Splicing

Explanation: **Explanation:** The core concept tested here is the functional diversity of RNA molecules beyond simple protein coding. **Why "Post-translational modification" is the correct answer:** Post-translational modifications (PTMs) involve the chemical modification of proteins *after* they have been synthesized by the ribosome. These processes (e.g., phosphorylation, glycosylation, hydroxylation) are catalyzed exclusively by **enzymes (proteins)**, such as kinases or glycosyltransferases. RNA does not play a direct catalytic or structural role in these modifications. **Why the other options are incorrect:** * **Post-transcriptional modification:** RNA is directly involved here. For example, **snoRNAs** (small nucleolar RNAs) guide the methylation and pseudouridylation of ribosomal RNA (rRNA). * **DNA replication:** RNA is essential for the initiation of DNA synthesis. DNA polymerase cannot start *de novo*; it requires an **RNA primer** synthesized by the enzyme Primase. Additionally, **Telomerase** (a ribonucleoprotein) uses an internal RNA template to extend chromosome ends. * **Splicing:** This is a major post-transcriptional process mediated by the **Spliceosome**, which is composed of **snRNAs** (U1, U2, U4, U5, U6) and proteins. The snRNAs are the actual catalytic components (ribozymes) that remove introns. **High-Yield NEET-PG Pearls:** * **Ribozymes:** RNA molecules with catalytic activity. Examples include Peptidyl transferase (28S rRNA in eukaryotes), SnRNAs in splicing, and RNase P. * **RNA as a Primer:** In DNA replication, the primer is a short fragment of RNA (~10 nucleotides), not DNA. * **miRNA & siRNA:** These are small non-coding RNAs involved in **gene silencing** (RNA interference), a frequent topic in genomic medicine. * **Translation:** Remember that the ribosome itself is a ribozyme; the formation of peptide bonds is catalyzed by RNA, not a protein enzyme.

Question 396: The phenomenon where subsequent generations are at risk of earlier and more severe disease, is known as?

A. Anticipation (Correct Answer)
B. Pleiotrophy
C. Imprinting
D. Mosaicism

Explanation: **Explanation:** **Anticipation** is the correct answer. It refers to the genetic phenomenon where a hereditary disease increases in severity and/or presents at an earlier age of onset in successive generations. This is most commonly associated with **Trinucleotide Repeat Expansion disorders**. As the gene is passed from parent to offspring, the number of repeats often increases (expands) during gametogenesis, leading to more profound protein dysfunction in the next generation. **Analysis of Incorrect Options:** * **Pleiotropy:** Occurs when a single gene mutation affects multiple, seemingly unrelated phenotypic traits or organ systems (e.g., Marfan Syndrome affecting the eyes, heart, and skeleton). * **Imprinting:** Refers to the epigenetic phenomenon where the expression of a gene depends on whether it was inherited from the mother or the father (e.g., Prader-Willi and Angelman syndromes). * **Mosaicism:** The presence of two or more populations of cells with different genotypes in one individual, derived from a single zygote due to post-zygotic mutations. **High-Yield Clinical Pearls for NEET-PG:** * **Classic Examples of Anticipation:** Huntington’s Disease (CAG repeats), Fragile X Syndrome (CGG), Myotonic Dystrophy (CTG), and Friedreich’s Ataxia (GAA). * **Parental Influence:** In **Huntington’s**, expansion occurs more severely during **paternal** transmission (spermatogenesis). In **Fragile X**, expansion occurs during **maternal** transmission (oogenesis). * **Threshold Effect:** Symptoms usually appear only after the number of repeats exceeds a specific "pre-mutation" threshold.

Question 397: Which enzyme is primarily responsible for mRNA synthesis?

A. RNA polymerase I
B. RNA polymerase II (Correct Answer)
C. Primase
D. Topoisomerase

Explanation: ### Explanation In eukaryotes, transcription is carried out by three distinct RNA polymerases, each specialized for synthesizing specific types of RNA. **Why RNA Polymerase II is Correct:** **RNA polymerase II** is the enzyme responsible for the synthesis of **pre-messenger RNA (pre-mRNA)**, which is subsequently processed into mature mRNA for translation into proteins. It also synthesizes most **snRNA** (small nuclear RNA involved in splicing) and **microRNA** (miRNA). Its activity is highly regulated and occurs within the nucleoplasm. **Analysis of Incorrect Options:** * **RNA Polymerase I:** Located in the nucleolus, it is responsible for synthesizing the **45S pre-rRNA** (which matures into 18S, 28S, and 5.8S ribosomal RNA). *Mnemonic: I, II, III = R, M, T (rRNA, mRNA, tRNA).* * **Primase:** This is a specialized **DNA-dependent RNA polymerase** involved in DNA replication. It synthesizes short RNA primers necessary for DNA polymerase to initiate synthesis on the leading and lagging strands. * **Topoisomerase:** These enzymes (Type I and II) manage DNA supercoiling during replication and transcription by creating transient breaks in the DNA phosphodiester backbone. They do not synthesize RNA. **High-Yield Clinical Pearls for NEET-PG:** * **Alpha-amanitin Sensitivity:** RNA Polymerase II is **highly sensitive** to $\alpha$-amanitin (found in *Amanita phalloides* or "death cap" mushrooms). Ingestion leads to severe liver failure due to the inhibition of mRNA synthesis. * **RNA Polymerase III:** Responsible for synthesizing **tRNA** and **5S rRNA**. * **Prokaryotes:** Unlike eukaryotes, bacteria use a **single RNA polymerase** (a multisubunit complex) to synthesize all types of RNA. * **Rifampicin:** Inhibits bacterial RNA polymerase by binding to the $\beta$-subunit, making it a cornerstone of anti-tubercular therapy.

Question 398: All of the following are true about a genomic library, EXCEPT?

A. It is a collection of cloned DNA fragments.
B. Screening is done by oligonucleotide probes.
C. Only exons are present. (Correct Answer)
D. Vectors are used to carry and replicate the fragments.

Explanation: **Explanation:** The core concept distinguishing a **Genomic Library** from a **cDNA Library** is the source material. A genomic library is created by taking the entire nuclear DNA of an organism, digesting it with restriction enzymes, and cloning the resulting fragments. **Why Option C is the correct answer (The Exception):** In eukaryotes, genomic DNA contains both **coding regions (exons)** and **non-coding regions (introns, promoters, and enhancers)**. Therefore, a genomic library contains the entire genome, including introns. In contrast, a **cDNA library** is synthesized from mature mRNA (where introns have already been spliced out), meaning it contains **only exons**. **Analysis of Incorrect Options:** * **Option A:** True. By definition, a library is a collection of DNA fragments that have been inserted into host cells for storage and propagation. * **Option B:** True. To find a specific gene within the thousands of clones in a library, researchers use labeled **oligonucleotide probes** that are complementary to the sequence of interest (Colony Hybridization). * **Option D:** True. Vectors (such as plasmids, bacteriophages, BACs, or YACs) are essential vehicles used to carry the DNA fragments into host bacteria (like *E. coli*) for replication. **High-Yield Clinical Pearls for NEET-PG:** * **Genomic Library:** Represents the entire genome; same for every cell in an organism. Useful for studying gene structure, introns, and regulatory elements. * **cDNA Library:** Represents only the "expressed" genes; varies from tissue to tissue (e.g., a liver cDNA library differs from a brain cDNA library). * **Vector Capacity:** For large genomic fragments, **YACs (Yeast Artificial Chromosomes)** have the largest capacity (up to 1000 kb), followed by **BACs (Bacterial Artificial Chromosomes)**.

Question 399: During protein biosynthesis, high-energy bonds are NOT utilized in which one of the following steps?

A. Formation of aminoacyl-tRNA
B. Binding of aminoacyl-tRNA to the A site of the ribosome
C. Formation of the peptide bond (peptidyl transferase step) (Correct Answer)
D. Translocation step

Explanation: ### Explanation The process of translation is energy-intensive, requiring the hydrolysis of high-energy phosphate bonds (ATP and GTP) at various stages. However, the actual formation of the peptide bond is a unique exception. **1. Why Option C is Correct:** The formation of the peptide bond is catalyzed by **peptidyl transferase** (a ribozyme component of the large ribosomal subunit). This step does **not** require the hydrolysis of a new high-energy phosphate bond (ATP or GTP). Instead, it utilizes the **inherent energy** stored in the high-energy ester bond between the amino acid and its tRNA, which was previously created during the "charging" phase. The reaction is essentially an energetically neutral transesterification. **2. Why the Other Options are Incorrect:** * **A. Formation of aminoacyl-tRNA:** This is the "charging" step catalyzed by aminoacyl-tRNA synthetase. It requires the hydrolysis of **ATP to AMP + PPi** (equivalent to 2 high-energy bonds). * **B. Binding of aminoacyl-tRNA to the A site:** This step requires **EF-Tu** (in prokaryotes) or **eEF-1** (in eukaryotes) and the hydrolysis of **one GTP**. * **D. Translocation:** The movement of the ribosome along the mRNA requires **EF-G** (prokaryotes) or **eEF-2** (eukaryotes) and the hydrolysis of **one GTP**. **Clinical Pearls & High-Yield Facts:** * **Energy Tally:** For every single amino acid added to a polypeptide chain, **4 high-energy bonds** are consumed (2 from ATP during charging, 1 for A-site binding, and 1 for translocation). * **Ribozyme Activity:** Peptidyl transferase is not a protein but an RNA enzyme (23S rRNA in prokaryotes, 28S rRNA in eukaryotes). * **Antibiotic Link:** **Chloramphenicol** specifically inhibits the peptidyl transferase enzyme in 50S bacterial ribosomes, making it a classic target for pharmacological inhibition.

Question 400: Which of the following is true about stop codons?

A. Three codons code for one amino acid.
B. Three codons code for the entire DNA.
C. Three codons code for the entire RNA.
D. Three codons act as terminator codons. (Correct Answer)

Explanation: ### Explanation **1. Why Option D is Correct:** In the genetic code, there are **64 possible codons** (triplets of nucleotides). While 61 codons are "sense codons" that specify amino acids, **three codons** do not code for any amino acid. These are known as **Stop Codons** or **Terminator Codons**: * **UAA** (Ochre) * **UAG** (Amber) * **UGA** (Opal) When a ribosome encounters these codons during translation, no corresponding tRNA binds to them. Instead, **Release Factors (RF)** recognize these sequences, triggering the hydrolysis of the bond between the peptide chain and the tRNA, thereby terminating protein synthesis. **2. Why Other Options are Incorrect:** * **Option A:** This is a misunderstanding of the "Degeneracy" of the genetic code. While multiple codons can code for the *same* amino acid (e.g., six codons for Leucine), stop codons specifically code for *no* amino acid. * **Options B & C:** Codons do not "code for" DNA or RNA. Codons are the *units* of the genetic code found within mRNA that dictate the sequence of amino acids in a protein. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **Nonsense Mutation:** A point mutation that changes a sense codon into a stop codon, leading to a truncated (shortened) and usually non-functional protein. * **Read-through Mutations:** Mutations that change a stop codon into a sense codon, resulting in an abnormally long protein. * **Exceptions:** In human **mitochondria**, the genetic code varies slightly; for example, **UGA** codes for Tryptophan instead of acting as a stop codon. * **Mnemonic to remember stop codons:** * **U** **A**re **A**way (UAA) * **U** **A**re **G**one (UAG) * **U** **G**o **A**way (UGA)

Practice by Chapter

DNA Replication and Repair Mechanisms

Practice Questions

Transcription Factors and Gene Regulation

Practice Questions

Epigenetics and DNA Methylation

Practice Questions

RNA Processing and Splicing

Practice Questions

miRNA and RNA Interference

Practice Questions

Protein Synthesis and Post-Translational Modifications

Practice Questions

Genomics and Human Genome Project

Practice Questions

Single Nucleotide Polymorphisms

Practice Questions

Gene Therapy Approaches

Practice Questions

CRISPR-Cas9 and Genome Editing

Practice Questions

DNA Fingerprinting and Forensics

Practice Questions

Molecular Basis of Genetic Diseases

Practice Questions

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