Methods for DNA sequencing In classical molecular biology, which approaches can be used to determine the nucleotide sequence of DNA?

Introduction:
Two foundational approaches established DNA sequencing as a routine laboratory procedure. Knowing their names and principles is essential context for modern high throughput methods that evolved from these techniques.

Given Data / Assumptions:

• Chemical degradation refers to the Maxam Gilbert method.
• Chain termination refers to the Sanger method using dideoxynucleotides.
• Focus on historically validated approaches rather than speculative physical methods.

Concept / Approach:

The Maxam Gilbert approach uses base specific chemical cleavage followed by gel separation to read sequence. The Sanger approach uses polymerase driven synthesis that terminates at labeled dideoxynucleotides, allowing readout by size separation. Both accurately recover base order.

Step-by-Step Solution:

Verification / Alternative check:

Classical sequencing of phage and plasmids used these methods successfully for decades, later automated with fluorescent labels leading to capillary sequencing instruments.

Why Other Options Are Wrong:

Purely physical optical approaches without chemistry were not the standard historical methods. Random shearing without detection cannot produce a sequence readout.

Common Pitfalls:

Confusing chain termination with chain elongation only, or assuming chemical cleavage is obsolete and therefore incorrect. Both are valid methods even if one is now rarely used.

Final Answer:

Both chemical degradation and chain termination methods