Whole genome shotgun sequencing primarily relies on which core strategy to reconstruct an entire genome efficiently from DNA?

Introduction / Context:
Genome projects often use shotgun approaches to accelerate sequencing and assembly. The hallmark of shotgun methodology is breaking the genome into many small pieces, sequencing each independently, and then using computational overlap to reconstruct the original sequence.

Given Data / Assumptions:

• Random fragmentation produces overlapping reads.
• High coverage enables accurate consensus sequence.
• Assembly software aligns overlaps to build contigs and scaffolds.

Concept / Approach:
In whole genome shotgun sequencing, DNA is randomly sheared to create numerous fragments. Each fragment is cloned or directly sequenced, generating a large number of short reads. Overlap layout consensus or de Bruijn graph algorithms assemble these reads into longer sequences. The efficiency comes from parallel processing of many small pieces rather than laborious mapping of large clones.

Step-by-Step Solution:
Identify the essential feature: random fragmentation and massive parallel sequencing. Note that reconstruction depends on overlapping reads with sufficient depth. Match this to the option describing thousands of small randomly cloned fragments. Select the shotgun defining strategy accordingly.

Verification / Alternative check:
Historical genome projects (for example, bacterial genomes and later larger eukaryotes) demonstrated rapid progress using shotgun approaches with high coverage and computational assembly, validating the core strategy.

Why Other Options Are Wrong:

• Sequencing a few large clones: characteristic of hierarchical methods, not shotgun.
• Sequencing intact chromosomes: not feasible with standard platforms and not the shotgun principle.
• All of the above: mixes incompatible strategies.

Common Pitfalls:
Confusing hierarchical clone by clone mapping with shotgun; the latter emphasizes randomness and scale rather than stepwise mapping.

Final Answer:
rapidly sequencing thousands of small randomly cloned fragments