Molecular Basis of Inheritance Set-6

Q1. A eukaryotic gene's coding sequence (CDS) is 1233 nucleotides long and includes the stop codon at its 3' end. How many amino acids are present in the translated polypeptide?

Q2. Glycine is encoded by four codons $GGU,\;GGC,\;GGA,\;GGG$. Using standard wobble rules in which inosine (I) at the 5'-position of the tRNA anticodon can pair with $U,\;C$ or $A$, what is the minimum number of distinct tRNA species required to recognise all four glycine codons?

Q3. Assertion (A): Mutations in the promoter region of a eukaryotic gene always lead to a decrease in that gene's transcription level.
Reason (R): Changes in promoter sequence alter the binding affinity of transcription factors and the basal transcription machinery, which can either increase or decrease transcription initiation.

Q4. A PCR reaction starts with a single double‑stranded DNA template. Ideal amplification doubles product every cycle, giving $2^n$ copies after $n$ cycles. If the per‑cycle efficiency is only 90% (effective multiplication factor per cycle $=1+E=1.9$), what is the approximate number of target molecules after 30 cycles?

Q5. In steady state, mRNA concentration is given by $[{\rm mRNA}]_{ss}=\dfrac{k_s}{k_d}$ where $k_s$ is transcription rate and $k_d$ is degradation rate; half‑life $t_{1/2}=\dfrac{\ln 2}{k_d}$. A mutation increases $k_s$ threefold but reduces mRNA half‑life to one‑half of the original value. What is the fold change in steady‑state mRNA level?

Q6. A circular bacterial chromosome of length $4.6\times10^{6}$ base pairs initiates replication at a single origin and proceeds bidirectionally. If each replication fork progresses at $1000\ \text{nucleotides s}^{-1}$, approximately how long (in minutes) will it take to complete replication of the chromosome? (Assume replication is simultaneous in both directions and neglect pauses.)

Q7. In E. coli, Dam methylation transiently marks the parental strand at GATC sites after replication. Consider a replication error that produces a $\mathrm{C}\!\cdot\!\mathrm{A}$ mismatch where the parental strand carries C (methylated) and the newly synthesized strand carries A (unmethylated). Which outcome is most likely due to the bacterial mismatch-repair system?

Q8. A bacterial cell is merodiploid: its chromosome carries a lac operon with an operator constitutive mutation $O^{c}$ (operator cannot bind repressor), while the same cell contains an F' plasmid encoding a wild-type lacI$^{+}$ repressor. What is the expected expression behaviour of the chromosomal lac structural genes in absence and presence of lactose?

Q9. DNA polymerase misincorporates a nucleotide at probability $10^{-5}$ per base per replication. Proofreading corrects $99\%$ of such misincorporations. Post-replicative mismatch repair recognises the parental (methylated) strand and directs repair to the new strand $99\%$ of the time. What is the probability that a single misincorporation at that base will become a permanent mutation after these two correction steps?

Q10. A bacterium has a nonsense mutation (stop codon $UAG$) at codon 120 of an essential gene P, producing a truncated inactive enzyme. A second-site mutation in a tRNA gene alters its anticodon so that the tRNA now recognises $UAG$ and inserts tyrosine (a suppressor tRNA). Which statement most accurately predicts the likely consequences of this suppressor appearing in the population?

Q11. A eukaryotic gene's pre-mRNA contains exons totaling $912$ nucleotides and introns totaling $360$ nucleotides. After splicing, translation begins at the first AUG at the 5'-end of the first exon and terminates at a stop codon located immediately after the last exon; the stop codon is included within the $912$-nt exon sequence. How many amino acids will the translated polypeptide contain (excluding the stop codon)?

Q12. The pre-mRNA of a eukaryotic gene has four exons with lengths $E_1=240$ nt, $E_2=151$ nt, $E_3=153$ nt and $E_4=150$ nt. Translation starts at the AUG at the 5'-end of $E_1$ and ends at the stop codon at the 3'-end of $E_4$. Which alternative splicing event will produce a shorter polypeptide that lacks the protein domain encoded by exon $E_3$ but retains the original reading frame (i.e., causes no downstream frameshift)?

Q13. In a eukaryotic chromosome replication origins are on average $60\ \text{kb}$ apart and each origin fires bidirectionally. If the average Okazaki fragment synthesized on the lagging strand is $200$ nucleotides long, approximately how many Okazaki fragments will be produced by a single replication fork before it meets the converging fork from the adjacent origin?

Q14. A point mutation in exon 4 of a human gene changes the codon $5'$–GAA–$3'$ to $5'$–GAG–$3'$ (both code for glutamic acid). However, analysis of mature mRNA shows exon 4 is completely skipped in transcripts from the mutant allele, producing a shorter mRNA. Which molecular explanation best accounts for exon 4 skipping despite the mutation being synonymous at the amino-acid level?

Q15. An open reading frame begins at an AUG start codon. Two independent mutations occur immediately downstream of the start codon: Mutation X inserts $5$ nucleotides at that position; Mutation Y inserts $6$ nucleotides at the same position. Which statement is most likely regarding the effect of these mutations on the translated polypeptide?