Paper I
Question
Mutation.
Answer
A mutation is a stable, heritable change in the nucleotide sequence of an organism’s DNA, arising either spontaneously (random errors during DNA replication, or spontaneous chemical changes such as tautomeric shifts/depurination) or induced by exposure to mutagenic agents (UV radiation, chemical mutagens, ionizing radiation).
Types (by molecular mechanism):
- Point mutation — substitution of a single nucleotide base:
- Missense — changes the codon to specify a different amino acid.
- Nonsense — changes a codon to a premature stop codon, truncating the protein.
- Silent — the changed codon still specifies the same amino acid (due to codon degeneracy), with no effect on the protein.
- Frameshift mutation — insertion or deletion of a number of bases not divisible by three, shifting the reading frame downstream of the mutation and typically producing a completely altered, often non-functional protein.
- Deletion/insertion of larger segments — loss or gain of a stretch of DNA, which can remove or add entire genes/gene segments.
Significance in microbiology:
- Antibiotic resistance — spontaneous chromosomal mutations can alter a drug target (e.g., DNA gyrase mutations conferring fluoroquinolone resistance, RNA polymerase mutations conferring rifampicin resistance) or reduce drug uptake/increase efflux.
- Antigenic variation — mutations in surface antigen genes allow immune evasion (e.g., antigenic drift in influenza virus).
- Attenuation — deliberately selected/induced mutations reduce a pathogen’s virulence while preserving immunogenicity, the principle behind live attenuated vaccines.
- Selection — antibiotics/host immune pressure do not cause resistance mutations directly but select for pre-existing resistant mutants within a large bacterial population, allowing them to outgrow susceptible organisms — the basis of the emergence of drug resistance under selective antibiotic pressure.