Molecular Basis of Inheritance, Gene Expression, Regulation, Viruses, and Evolution

Chapter 16: Molecular Basis of Inheritance

DNA Structure & Evidence

The structure of DNA and the evidence supporting its role as the genetic material are foundational concepts in molecular biology.

• Double Helix: DNA consists of two strands twisted into a double helix, as described by Watson & Crick.

• Antiparallel Strands: The two DNA strands run in opposite directions (5′ to 3′ and 3′ to 5′).

• Sugar-Phosphate Backbone: Each strand is composed of a backbone made of alternating sugars (deoxyribose) and phosphate groups.

• Complementary Base Pairing: Adenine (A) pairs with Thymine (T), and Guanine (G) pairs with Cytosine (C).

• Evidence DNA Is Genetic Material:

  • Griffith’s transformation experiments showed that a "transforming principle" could transfer genetic traits.

  • Avery, MacLeod, McCarty identified DNA as the transforming principle.

  • Hershey-Chase blender experiment confirmed DNA, not protein, is the genetic material in phages.

DNA Replication

DNA replication is the process by which DNA is copied before cell division, ensuring genetic continuity.

• Semiconservative Replication: Each new DNA molecule contains one old strand and one new strand.

• Origins of Replication: Replication begins at specific sites called origins; replication forks move bidirectionally.

• Key Enzymes:

  • Helicase: Unwinds the DNA helix.

  • Single-strand binding proteins: Stabilize unwound DNA.

  • Primase: Synthesizes RNA primers.

  • DNA Polymerase: Adds nucleotides in the 5′ → 3′ direction.

  • DNA Pol I: Replaces RNA primers with DNA.

  • Ligase: Joins Okazaki fragments on the lagging strand.

• Leading vs Lagging Strand:

  • Leading Strand: Synthesized continuously.

  • Lagging Strand: Synthesized discontinuously as Okazaki fragments.

• DNA Repair:

  • Proofreading by DNA polymerase.

  • Mismatch repair corrects errors missed during replication.

  • Nucleotide excision repair removes damaged DNA segments.

• End Replication (Eukaryotes):

  • Telomeres protect chromosome ends.

  • Telomerase extends telomeres in germ cells.

Prokaryotic vs Eukaryotic Replication

Comparison of DNA replication features in prokaryotes and eukaryotes:

Feature	Prokaryotes	Eukaryotes
Chromosomes	Circular	Linear
Origins	One	Many
Telomeres	No	Yes
Speed	Faster	Slower

Chromatin Packing

DNA is packaged in the cell nucleus through several hierarchical levels, affecting gene expression.

• Levels of Packing:

  1. DNA double helix

  2. Nucleosomes (DNA wrapped around histone proteins)

  3. 30 nm fiber

  4. Loop domains

  5. Metaphase chromosome

• Euchromatin: Less condensed, transcriptionally active.

• Heterochromatin: Highly condensed, transcriptionally inactive.

Chapter 17: Gene Expression

From Gene to Protein

Gene expression involves the conversion of genetic information from DNA into functional proteins, following the central dogma.

• Central Dogma: DNA → RNA → Protein.

• Beadle & Tatum: Established the "one gene–one enzyme" hypothesis.

Transcription

Transcription is the synthesis of RNA from a DNA template, occurring in the nucleus (eukaryotes) or cytoplasm (prokaryotes).

• Key Components:

  • RNA polymerase

  • Promoter (e.g., TATA box)

  • Terminator sequence

• Steps:

  1. Initiation

  2. Elongation (RNA synthesized 5′ → 3′)

  3. Termination

Eukaryotic RNA Processing

• 5′ cap added for stability and ribosome binding.

• 3′ poly-A tail added for stability.

• Splicing removes introns and joins exons.

• Alternative splicing allows multiple proteins from one gene.

Translation

Translation is the process by which ribosomes synthesize proteins using mRNA as a template.

• Components:

  • mRNA

  • tRNA (with anticodon)

  • Ribosome (A, P, E sites)

• Steps:

  1. Initiation (start codon AUG)

  2. Elongation

  3. Termination (stop codon)

• Multiple Polypeptides:

  • Prokaryotes: Transcription and translation occur simultaneously.

  • Eukaryotes: mRNA exits nucleus; polysomes form in cytoplasm.

Mutations & Gene Concept

Mutations are changes in DNA sequence that can affect gene function and protein structure.

• Types of Mutations:

  • Point mutations: Silent, Missense, Nonsense

  • Insertions & deletions: Can cause frameshift mutations

• Effects: Mutations can alter protein structure/function.

• Gene: Sequence that codes for a functional RNA or polypeptide.

Chapter 18: Regulation of Gene Expression

Operons in Prokaryotes

Operons are clusters of genes regulated together, common in prokaryotes.

• trp Operon (Repressible):

  • Default state: ON

  • Tryptophan acts as a co-repressor

  • Used for anabolic pathways

• lac Operon (Inducible):

  • Default state: OFF

  • Lactose inactivates the repressor

  • CAP-cAMP enhances transcription when glucose is low

Eukaryotic Gene Regulation

Gene expression in eukaryotes is regulated at multiple levels, allowing for complex control and cell specialization.

• Chromatin modification

• Transcriptional control

• RNA processing

• mRNA degradation

• Translational control

• Post-translational modification

Differential Gene Expression

• Same genome, different genes expressed in different cell types

• Leads to specialized cell types

• Driven by transcription factors and epigenetic marks

Chapter 19: Viruses

Virus Structure

Viruses are non-cellular entities that require host cells for replication.

• Nucleic acid (DNA or RNA)

• Protein coat (capsid)

• Some have a viral envelope

• Obligate intracellular parasites

Viral Replication

• Lytic Cycle: Virus replicates immediately; host cell is lysed.

• Lysogenic Cycle: Viral genome integrates as a prophage; can switch to lytic cycle.

Prions

• Infectious proteins

• Cause neurodegenerative diseases

• No nucleic acid

• Induce misfolding of normal proteins

Chapter 22: Evolution by Natural Selection

Darwin’s Concept

Darwin proposed that evolution occurs through natural selection, leading to adaptation and diversity.

• Descent with Modification: Populations evolve, not individuals.

• Contrasted with fixity of species and special creation.

Natural Selection

• Variation exists within populations.

• Overproduction of offspring.

• Differential survival and reproduction.

• Leads to adaptation over time.

Evidence for Evolution

• Fossil record

• Comparative anatomy

• Molecular homology

• Biogeography

• Direct observation

Chapter 23: Populations & Evolution

Genetic Variation

Genetic variation is essential for evolution and arises from several sources.

• Mutation

• Sexual reproduction

• Gene flow

Hardy-Weinberg Equilibrium

The Hardy-Weinberg principle describes a population that is not evolving.

• Allele and genotype frequencies remain constant.

• Conditions:

  • No mutation

  • Random mating

  • Large population

  • No selection

  • No migration

Hardy-Weinberg Equation:

$p^2 + 2pq + q^2 = 1$

$p + q = 1$

Forces That Change Allele Frequencies

• Natural selection

• Genetic drift (bottleneck effect, founder effect)

• Gene flow

Adaptation

• Traits that increase fitness

• Result of natural selection

Chapter 24: Origin of Species

Biological Species Concept

A species is defined as a group of organisms that can interbreed and produce fertile offspring.

• Groups that can interbreed and produce fertile offspring

Reproductive Barriers

Reproductive barriers prevent species from interbreeding.

• Prezygotic Barriers:

  • Habitat isolation

  • Temporal isolation

  • Behavioral isolation

  • Mechanical isolation

  • Gametic isolation

• Postzygotic Barriers:

  • Reduced hybrid viability

  • Reduced hybrid fertility

  • Hybrid breakdown

Speciation Mechanisms

• Allopatric Speciation: Geographic isolation; most common.

• Sympatric Speciation: No geographic barrier; often involves polyploidy or sexual selection.

Hybrid Zones

• Possible outcomes:

  • Reinforcement

  • Fusion

  • Stability

Rates of Speciation

• Rapid: punctuated equilibrium

• Slow: gradualism

• May involve few or many genes