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Learning path

Full curriculum

Full curriculum
  1. Semiconservative DNA replication from origins of replication
  2. DNA damage and mutations as distinct genome changes
  3. Post-replicative mismatch repair
  4. Cyclin-CDK control and checkpoints of cell-cycle progression
  5. DNA sequence substitutions, insertions and deletions
  6. Coding-sequence consequences of base substitutions
  7. Coding-sequence consequences of insertions and deletions
  8. Sequence alignment as a hypothesis of positional homology
  9. Heritable variation as the raw material for evolutionary change
  10. Evolution as change in heritable population composition across generations

Unit content

DNA damage and mutations as distinct genome changes

DNA damage and mutation are related but different concepts.

A DNA lesion is a chemical or structural alteration of DNA that disrupts its ordinary molecular form. Examples include a chemically modified base, a missing base, a covalent linkage between neighboring bases, or a break in the sugar-phosphate backbone.

A mutation is a stable change in nucleotide sequence that can be copied when that DNA is replicated.

This distinction matters because damage can be repaired without changing the encoded sequence, while unrepaired or incorrectly repaired damage can sometimes become a mutation after DNA synthesis.

From lesion to mutation

Suppose a chemical reaction changes a cytosine base so that it now pairs preferentially with A instead of G. Immediately after the chemical change, the DNA is damaged but the original sequence information may still be recoverable from the opposite strand.

If replication occurs before correct repair, a polymerase may place an A opposite the altered base. After another round of copying, one descendant DNA molecule can contain a stable T-A pair where the original molecule contained C-G. At that point the sequence itself has changed: a mutation has become fixed.

Schematically:

normal DNA
   ↓ damage
DNA lesion
   ↓ inaccurate copying or repair
sequence change
   ↓ replication
stable mutation

Mutations can also originate as replication errors

Not every mutation begins with an external DNA-damaging event. A mismatch created during ordinary DNA replication can escape proofreading and post-replicative repair. Once subsequent replication makes the altered sequence part of a normal complementary base pair, the change is no longer recognized simply as a mismatch.

Sequence change does not imply a particular effect

A mutation can occur in a protein-coding region, a regulatory sequence, a noncoding RNA gene, or DNA with no currently known functional consequence. Its biological effect depends on where the sequence changes and what that sequence normally does.

Some mutations alter molecular function strongly, some alter it subtly, and some have little or no detectable effect in a particular environment.

DNA repair therefore protects sequence information, not merely the physical integrity of the molecule. The key boundary is: damage describes an abnormal molecular state; mutation describes a stable altered sequence state.