Unit 3 Revision – Mutations, Antigenic Drift & Shift, Selection Pressure

Shape specificity: Antibodies (and proteins in general) function based on their specific 3D shape (tertiary/quaternary folding).
Altering protein shape (e.g., via mutation or misfolding) can significantly impact or nullify its activity.
Antibody structure: Heavy chains are internal, light chains are external.

W: mRNA (messenger RNA)
X: tRNA (transfer RNA) carrying an amino acid for polypeptide synthesis.
Y: Ribosome, which reads mRNA from $3\prime\rightarrow 5\prime$ to synthesize protein.
Z: Anticodon (on tRNA), which pairs with codons on mRNA.
Central Dogma Link: DNA mutation $\rightarrow$ altered mRNA codon $\rightarrow$ altered amino acid sequence $\rightarrow$ altered protein structure and function.
Codon Table Use: Ability to read 64-cell codon charts and convert between DNA, mRNA, anticodon, and amino acid sequences.

Antigenic drift:
- Cause: Minor, gradual changes due to point mutations (often single amino acid substitutions) in surface antigens.
- Effect: Subtle changes, leading to new variants (e.g., annual influenza variants, accumulating SARS-CoV-2 mutations).
- Mnemonic: “Drift = drifting slowly down the beach.”
Antigenic shift:
- Cause: Major, abrupt genetic reassortment from co-infection of a host (e.g., pigs with human and avian flu) by two or more different viral strains.
- Effect: Produces a novel viral subtype unfamiliar to the immune system, often triggering pandemics.
- Mnemonic: “Shift = shifting gears abruptly.”
- Pigs often act as “mixing vessels” for influenza viruses.

Point mutation: Change in a single nucleotide.
Substitution: One or more bases replaced by the same number of bases.
Deletion: Removal of one or more bases.
Insertion: Addition of one or more extra bases.
Frameshift mutation: Any insertion or deletion not in multiples of three bases; drastically changes the reading frame, altering all subsequent codons and amino acids.

Germline mutation: Occurs in gametes (sperm or egg).
- Result: Present in every cell of the offspring.
- Inheritance: Heritable (passed down to future generations).
Somatic mutation: Occurs in body cells (post-zygotic).
- Result: Limited to a subset of tissues; creates a mosaic.
- Inheritance: Not passed on to offspring.
- Example: Wild-type mRNA codon $ext{GCU}$ mutated to $ext{UCU}$ in a fruit-fly gamete resulted in insecticide resistance across multiple flies (indicating germline).

Neutral (silent) mutation: Codon change still codes for the same amino acid due to degeneracy of the genetic code; no change in protein function or fitness.
Beneficial mutation: Increases an organism's fitness in a specific environment.
- Examples: Insecticide resistance in insects, antibiotic resistance in bacteria, sickle-cell allele in malarial regions (for heterozygotes).
Harmful mutation: Reduces an organism's fitness.
- Examples: Sickle-cell anemia (homozygous recessive) in non-malarial regions, cystic fibrosis, albinism.
Sickle-Cell Anemia Case Study:
- Cause: Single nucleotide substitution in the $\beta$ -globin gene.
- Result: Production of HbS variant, leading to crescent-shaped red blood cells.
- Heterozygotes ( $ext{Hb}^A ext{Hb}^S$ ) gain significant protection against malaria, demonstrating environment-dependent fitness.

Genotype: The specific genetic makeup of an organism (e.g., alleles, nucleotide sequence).
Phenotype: The observable traits or characteristics of an organism, including its proteins (e.g., altered spike protein due to mutation).
Exam Tip: Always connect: mutation (genotype change) $ightarrow$ altered protein structure $ightarrow$ altered phenotype $ightarrow$ selection pressure.

Selection Pressure: Any environmental factor that differentially favors the survival and reproduction of individuals with certain phenotypes over others.
- Examples: Antibiotics, antivirals, predation, climate, pH, salinity.
- In viruses, host antibodies or antiviral drugs act as selection pressures, driving antigenic changes (like drift) to evade the immune response.
Antibiotic Resistance in Bacteria:
- Mechanism: Large bacterial populations coupled with high mutation rates generate constant genetic variation. Sub-lethal exposure to antibiotics allows rare resistant mutants to survive, replicate, and become dominant.
- Clinical Importance: Complete full antibiotic courses to minimize the selective window for resistant strains to proliferate.
Harvard “MEGA-Plate” Experiment (2016):
- Demonstrated rapid, stepwise evolution of antibiotic resistance. Bacteria conquered zones of increasing antibiotic concentration ( $0\times \rightarrow 1\times \rightarrow 10\times \rightarrow 100\times \rightarrow 1000\times$ ) through successive mutations. This visualised selection pressure in real-time.

Clearly define and contrast Antigenic drift and Antigenic shift, providing real-world examples.
Understand different mutation types (point, substitution, insertion, deletion, frameshift) and link them to their effects on codons and translation.
Distinguish between Germline and somatic mutations, emphasizing that only germline mutations affect future generations.
Explain how selection pressure drives the spread of beneficial mutations (e.g., insects vs. insecticide, bacteria vs. antibiotics, viruses vs. immunity).
Practice reading codon tables and tracing the flow of genetic information: DNA $<br>ightarrow$ mRNA $<br>ightarrow$ amino acid.
In explanations, establish a coherent chain of events: mutation $ightarrow$ change in protein structure $ightarrow$ altered phenotype $ightarrow$ selection pressure $ightarrow$ change in allele frequency.