Genetics Overview and History

Genetics

• The study of how traits are passed from parents to offspring.
• Genes are units of information about traits.

History of Genetics

• Mendel's Laws of Inheritance:
  • Inheritance of traits is determined by genes passed from parents.
  • Individuals inherit one gene from each parent for each trait.
  • Traits can be hidden but still passed on.
• Griffith transformation experiment:
  • Virulent (S-strain) bacteria have a smooth capsule, causing infection.
  • Non-virulent (R-strain) lacks the capsule, not causing infection.
  • Heat-killed S-strain mixed with live R-strain resulted in lethal infection.
  • Transformation factor transferred from S-strain enabled R-strain to become virulent.
• Oswald Avery:
  • Isolated a cell-free extract from S-strain.
  • This extract transformed living R-strain into both S-strain and R-strain cells.
  • Only DNase destroyed the "transforming principle", confirming DNA as the genetic material.
• Hershey-Chase Experiment:
  • A phage is a virus containing DNA and a protein coat.
  • Phages labeled with radioactive sulfur (protein) or phosphorous (DNA) infected bacteria.
  • Radioactive phosphorous was found in infected bacteria, proving DNA carries genetic information.
• Rosalind Franklin's X-ray Crystallography:
  • Identified two DNA configurations (a and b forms).
  • Proposed a double-helix structure with precise measurements for diameter, separation, and pitch.
• James Watson and Francis Crick:
  • DNA is a double-stranded, helical molecule.
  • The sugar-phosphate backbones form the outside of the helix.
  • Nitrogenous bases (A, C, G, T) pair inside, held by hydrogen bonds (A-T, C-G).
  • This structure is called the "genetic code".

Nucleic Acid Structure

• A nucleotide consists of a sugar, a phosphate group, and a nitrogenous base.
  • Purine bases: adenine and guanine
  • Pyrimidine bases: cytosine, thymine, and uracil
• Double helix structure:
  • Two sugar-phosphate backbones on the outside.
  • Nitrogenous bases paired inside, held by hydrogen bonds.
  • Strands run in opposite directions (antiparallel).
  • This orientation is important for DNA replication and interactions.

Differences between DNA and RNA

- **Sugar:** DNA contains deoxyribose; RNA contains ribose.
- **Bases:** DNA has thymine; RNA has uracil.
- **Pairing:** DNA (A-T, C-G); RNA (A-U, C-G).
- **Location:** DNA in the nucleus; RNA forms in the nucleolus and moves to cytoplasm.
- **Reactivity:**  DNA is more stable due to deoxyribose; RNA is reactive.

Types of RNA

• Messenger RNA (mRNA): Copies DNA code (transcription) and carries it to ribosomes for protein production.
• Transfer RNA (tRNA): Brings amino acids to ribosomes for protein synthesis.
• Ribosomal RNA (rRNA): A structural component of ribosomes.

DNA Supercoiling

• DNA folds up on itself to form tertiary structures.
• Supercoiling allows for compact packaging of circular DNA.
• Supercoiling changes the shape of DNA, making it more compact.
• DNA topoisomerases:
  • Regulate DNA supercoiling by winding and unwinding DNA strands.
  • Class I: Break one strand of DNA helix.
  • Class II: Break two strands of DNA helix.

The Flow of Genetic Information

• Replication (DNA synthesis): DNA makes a copy of itself.
• Protein Expression:
  • Transcription (RNA synthesis): DNA code is copied into RNA.
  • Translation (protein synthesis): RNA code is used to create protein.

DNA Replication

- **Semi-discontinuous:** Occurs in both directions but at different rates.
- **Semi-conservative:** New DNA contains one original and one newly synthesized strand.

• Three steps:
  • Initiation: Begins at the origin of replication (oric).
  • Propagation: Elongation of the new strand.
  • Termination: Process ends at a specific termination sequence in the DNA.

Replication Step 1: Initiation

• Enzymes:
  • Helicase: Separates DNA strands, forming the replication fork.
  • SSB protein: Binds to single strands to prevent them from rejoining.
  • DNA polymerase III: Synthesizes the new strand, adding complementary nucleotides (5'-3' direction).
  • DNA primase: Synthesizes short RNA primers to initiate DNA replication.
  • Ligase: Joins Okazaki fragments.

Replication Step 2: Elongation

• DNA Polymerase III functions:
  • Adds nucleotides in 5'-3' direction.
  • 3'-5' exonuclease activity: Proofreading for accuracy.
  • 5'-3' exonuclease activity: Removes RNA primers or damaged DNA.
• Semi-discontinuous replication:
  • The leading strand is synthesized continuously in 5'-3' direction.
  • Lagging strand is synthesized discontinuously, forming Okazaki fragments.
  • DNA polymerase I replaces RNA primers, and ligase joins fragments.

Replication Step 3: Termination

• Replication is stopped at specific termination sequence in DNA.
• Termination involves:
  • A termination site sequence.
  • A protein binding to the sequence to stop replication.

IL 1

• DNA uses thymine (T) instead of uracil (U) because:
  • Thymine is more stable than uracil, which is important for long-term storage of genetic information in DNA.
  • Uracil is prone to deamination (loss of an amino group), which can lead to mutations if not properly removed.
  • Thymine has a methyl group that helps protect it from deamination, ensuring the integrity of genetic code.