The Molecular Basis of Inheritance

Key Contributors to DNA Structure Discovery

The discovery of DNA's structure was a pivotal moment in biology, involving several key scientists.

• Rosalind Franklin: Used X-ray crystallography to produce images of DNA, revealing its helical structure.

• James Watson & Francis Crick: Built the first accurate model of DNA's double helix, using Franklin's data.

Experiments Demonstrating DNA as Genetic Material

Three landmark experiments established DNA as the molecule of heredity.

• Griffith's Transformation Experiment: Showed that a "transforming principle" could transfer genetic traits between bacteria.

• Avery, MacLeod, and McCarty: Identified DNA as the transforming principle in Griffith's experiment.

• Hershey-Chase Experiment: Used bacteriophages to demonstrate that DNA, not protein, is the genetic material.

Nucleic Acids: Types and Functions

Nucleic acids are essential biomolecules for storing and transmitting genetic information.

• DNA (Deoxyribonucleic Acid): Stores genetic information; double-stranded.

• RNA (Ribonucleic Acid): Transfers genetic information and assists in protein synthesis; single-stranded.

Structural Differences Between DNA and RNA

• Sugar: DNA contains deoxyribose; RNA contains ribose.

• Nitrogenous Bases: DNA: Adenine (A), Thymine (T), Cytosine (C), Guanine (G); RNA: Adenine (A), Uracil (U), Cytosine (C), Guanine (G).

• Strandedness: DNA is double-stranded; RNA is single-stranded.

Condensation (Dehydration) Synthesis of Nucleic Acids

Nucleotides are joined by phosphodiester bonds via condensation reactions, forming the backbone of DNA and RNA.

• Process: Removal of water to link the 5' phosphate of one nucleotide to the 3' hydroxyl of another.

Complementary Base Pairing in DNA

Base pairing ensures accurate replication and transcription.

• A pairs with T (via 2 hydrogen bonds)

• C pairs with G (via 3 hydrogen bonds)

Structure of a DNA Nucleotide

• Components: Deoxyribose sugar, phosphate group, nitrogenous base.

• Ends: 5' end (phosphate), 3' end (hydroxyl group).

DNA Double Helix and Antiparallel Configuration

DNA consists of two antiparallel strands twisted into a double helix.

• Antiparallel: One strand runs 5' to 3', the other 3' to 5'.

• Double Helix: Two strands coil around each other, stabilized by base pairing.

DNA Replication: Mechanism and Enzymes

DNA replication is the process by which DNA is copied before cell division.

• Semi-conservative Replication: Each new DNA molecule contains one old strand and one new strand.

• Origin of Replication: Specific sequence where replication begins.

• Replication Bubble & Fork: Unwinding creates a bubble and two forks for bidirectional replication.

Key Enzymes and Proteins

• Helicase: Unwinds DNA at the replication fork.

• Single-strand Binding Proteins: Stabilize unwound DNA.

• Topoisomerase: Relieves strain ahead of the fork.

• Primase: Synthesizes RNA primers.

• DNA Polymerase III: Adds nucleotides to the new strand.

• DNA Polymerase I: Replaces RNA primers with DNA.

• DNA Ligase: Joins Okazaki fragments on the lagging strand.

Leading vs. Lagging Strand

• Leading Strand: Synthesized continuously toward the replication fork.

• Lagging Strand: Synthesized discontinuously in Okazaki fragments away from the fork.

Okazaki Fragments and Primer Replacement

• Okazaki Fragments: Short DNA segments on the lagging strand.

• Primer Replacement: DNA Polymerase I replaces RNA primers with DNA; DNA Ligase seals gaps.

Telomeres and Telomerase

• Telomere: Repetitive DNA at chromosome ends, protects from degradation.

• Telomerase: Enzyme that extends telomeres, maintaining chromosome integrity.

DNA Condensation and Chromatin Structure

DNA is packaged to fit within the nucleus and regulate gene expression.

• Chromatin: DNA-protein complex; can be euchromatin (active) or heterochromatin (inactive).

• Histones: Proteins around which DNA winds, forming nucleosomes.

• Fibers: 10 nm (nucleosome), 30 nm (condensed chromatin).

Definitions

• Chromosome: Condensed DNA structure during cell division.

• Chromatin: DNA and associated proteins.

• Chromatid: One of two identical halves of a duplicated chromosome.

• Nucleosome: DNA wrapped around histone proteins.

Gene Expression: From Gene to Protein

Central Dogma and Gene Structure

The central dogma describes the flow of genetic information: DNA → RNA → Protein.

• Gene: DNA region coding for a functional product (protein or RNA).

• Protein Structure: Sequence of amino acids folded into a functional shape; enzymes catalyze biochemical reactions.

Beadle and Tatum's Contribution

Beadle and Tatum demonstrated that genes encode enzymes, leading to the "one gene-one enzyme" hypothesis.

Relationship Between DNA and Protein

• Nucleotide Sequence: Determines amino acid sequence in proteins via the genetic code.

Protein Synthesis: Transcription and Translation

Protein synthesis involves two main processes: transcription and translation.

• Transcription: DNA is copied into messenger RNA (mRNA) in the nucleus.

• Translation: mRNA is decoded into a polypeptide at the ribosome in the cytoplasm.

Types of RNA Involved

• mRNA: Carries genetic code from DNA to ribosome.

• tRNA: Transfers amino acids to the ribosome.

• rRNA: Structural and catalytic component of ribosomes.

Genetic Code and Codons

• Triplet Code: Three nucleotides (codon) specify one amino acid.

• Redundant: Multiple codons can code for the same amino acid.

• Universal: Same code used by almost all organisms.

Relationship Table

Mutations and Their Effects

• Point Mutation: Single nucleotide change (substitution, insertion, deletion).

• Frameshift Mutation: Insertion or deletion shifts reading frame, altering protein sequence.

• Silent Mutation: No change in amino acid.

• Missense Mutation: Changes one amino acid.

• Nonsense Mutation: Creates a stop codon, truncating protein.

Steps of Gene Expression

1. Transcription (DNA → RNA)

2. RNA Processing (in eukaryotes)

3. Translation (RNA → Protein)

4. Protein Folding and Modification

Transcription Process

• Initiation: RNA polymerase binds to promoter (often includes TATA box) with help from transcription factors.

• Elongation: RNA polymerase synthesizes RNA in 5' → 3' direction, reading DNA template 3' → 5'.

• Termination: RNA polymerase stops at terminator sequence.

RNA Processing in Eukaryotes

• Introns: Non-coding regions, removed.

• Exons: Coding regions, spliced together.

• Steps:

  1. Add 5' cap

  2. Add poly-A tail

  3. Splice out introns (via spliceosome)

  4. Export mature mRNA to cytoplasm

• Spliceosome: Complex of snRNPs and proteins that removes introns and joins exons.

Translation Process

• Initiation: Ribosome assembles at 5' end of mRNA; initiator tRNA binds start codon.

• Elongation: tRNAs bring amino acids; ribosome catalyzes peptide bond formation; tRNA moves through A, P, E sites.

• Termination: Stop codon recognized; release factor releases polypeptide.

Ribosome Structure

• Large and Small Subunits: Each composed of rRNA and proteins.

• A Site: Accepts incoming tRNA.

• P Site: Holds tRNA with growing polypeptide.

• E Site: Exit site for tRNA.

Polypeptide Modification

• Folding: Polypeptide folds into functional 3D shape.

• Post-translational Modifications: May include cleavage, addition of functional groups, or targeting to specific locations.

Summary Table: Key Terms and Functions

Key Equations and Concepts

• Chargaff's Rule:

• Direction of DNA Synthesis:

• Genetic Code: