Comprehensive Study Guide: Genetics, Molecular Biology, and Cell Function

Genetics

Sex-Linked Traits and Inheritance Patterns

Sex-linked traits are those whose genes are located on sex chromosomes (X or Y). Their inheritance patterns differ from autosomal traits due to the unique composition of sex chromosomes in males and females.

• Sex-Linked Traits: Genes on sex chromosomes, especially the X chromosome, require careful tracking in Punnett squares. Males (XY) are more likely to express recessive X-linked traits because they have only one X chromosome.

• Monohybrid vs. Dihybrid Crosses: Monohybrid crosses trace a single trait; dihybrid crosses trace two traits, assuming independent assortment (genes on separate chromosomes).

• Principle of Independent Assortment: Genes on different chromosomes separate independently during meiosis.

Patterns of Dominance

Genotype can be expressed in phenotype through various dominance relationships:

• Complete Dominance: One allele completely masks the other in heterozygotes.

• Incomplete Dominance: Neither allele is fully dominant; heterozygotes show an intermediate phenotype (e.g., red + white flowers = pink).

• Codominance: Both alleles are fully expressed in heterozygotes (e.g., black and white speckled chickens; ABO blood types where A and B are codominant).

• Polygenic Inheritance: Multiple genes contribute to a single trait (e.g., height, eye color).

• Pleiotropy: One gene affects multiple phenotypic traits.

• Epistasis: One gene masks or modifies the expression of another gene.

Gene Linkage and Chromosomal Complications

• Linked Genes: Genes located close together on the same chromosome tend to be inherited together.

• Crossing Over: Exchange of genetic material during meiosis can separate linked genes, but the closer the genes, the less likely they are to be separated.

• Non-Nuclear Genes: Some genes are found in mitochondria; mutations can cause disorders affecting energy production.

Environmental Effects and Carriers

• Environment: Phenotype is often determined by both genotype and environmental factors.

• Carriers: Heterozygotes for a recessive allele (especially disease alleles) are called carriers.

Lethal Alleles and Pedigree Analysis

• Lethal Recessive Alleles: Often due to mutations causing defective proteins; heterozygotes usually unaffected, but homozygotes lack functional protein.

• Lethal Dominant Alleles: Less common; persist if effects appear after reproductive age (e.g., Huntington's disease).

• Pedigrees: Diagrams tracing inheritance through families; use specific symbols for sex and affected status. Useful for determining mode of inheritance (dominant, recessive, sex-linked).

DNA Replication and Gene Expression

DNA Replication

DNA replication is a semiconservative process occurring before cell division, ensuring genetic continuity.

• Directionality: DNA polymerase adds nucleotides in the 5' to 3' direction.

• Origins of Replication: Bacteria have one; eukaryotes have multiple.

• Replication Fork: The site where DNA is unwound and replicated.

• Leading vs. Lagging Strand: Leading strand synthesized continuously; lagging strand synthesized in Okazaki fragments, later joined by DNA ligase.

• Key Enzymes: Helicase (unwinds DNA), topoisomerase (relieves tension), primase (synthesizes RNA primers), DNA polymerase I (replaces RNA primers), DNA ligase (joins fragments).

• Telomeres and Telomerase: Chromosome ends shorten with each division; telomerase extends telomeres in stem, germ, and cancer cells.

Central Dogma and Gene Expression

• Central Dogma: $\text{DNA} \rightarrow \text{RNA} \rightarrow \text{Protein}$

• Transcription: DNA is copied into RNA (mRNA, tRNA, rRNA, etc.).

• Translation: mRNA is decoded by ribosomes to build proteins; each codon (three nucleotides) specifies an amino acid.

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

• tRNA: Transfers specific amino acids to the ribosome; aminoacyl-tRNA synthetases attach amino acids to tRNAs.

Mutations and Their Effects

Types and Causes of Mutations

• Definition: Permanent changes in DNA sequence.

• Causes: DNA replication errors, radiation, free radicals.

• Types:

  • Point Mutations: Affect one or a few base pairs (substitution, silent, missense, nonsense).

  • Frameshift Mutations: Insertions/deletions that shift the reading frame.

  • Chromosomal Mutations: Affect large DNA segments (deletions, inversions, polyploidy, aneuploidy).

• Effects: Can be beneficial, neutral, or deleterious; source of genetic variation for evolution.

DNA Repair Mechanisms

• Proofreading: DNA polymerase corrects errors during replication.

• Mismatch Repair: Post-replication correction of mismatched bases.

• Mutator Genes: Involved in DNA repair; mutations can lead to cancer.

Transcription and Translation

Transcription

• Initiation: RNA polymerase binds to promoter (with sigma factor in bacteria; transcription factors in eukaryotes).

• Elongation: RNA nucleotides added in 5' to 3' direction.

• Termination: Specific signals end transcription (different in prokaryotes and eukaryotes).

• RNA Processing (Eukaryotes): Introns removed, exons spliced, 5' cap and poly(A) tail added.

• Alternative Splicing: Allows production of multiple proteins from one gene.

Translation

• Initiation: Small ribosomal subunit binds mRNA, initiator tRNA binds start codon, large subunit joins.

• Elongation: Amino acids added as tRNAs bring them to the ribosome; peptide bonds form.

• Termination: Stop codon reached; release factor causes ribosome to disassemble and release polypeptide.

• Polyribosomes: Multiple ribosomes translate a single mRNA simultaneously.

Control of Gene Expression

Levels of Regulation

• Transcriptional Control: Most energy efficient; involves repressors and activators.

• Translational Control: Regulates mRNA translation rate.

• Post-Translational Control: Modifies proteins after synthesis (e.g., ubiquitin tagging for degradation).

Operons and Regulatory Mechanisms (Prokaryotes)

• Operon: Cluster of genes transcribed as a single mRNA, regulated together (e.g., lac operon, trp operon).

• lac Operon: Repressor blocks transcription unless lactose is present.

• trp Operon: Repressor binds operator when tryptophan is abundant.

• Regulons: Groups of genes/operons regulated by the same regulatory proteins.

Epigenetics and Chromatin Remodeling (Eukaryotes)

• Epigenetics: Heritable changes in gene expression not involving changes to DNA sequence (e.g., DNA methylation, histone modification).

• Chromatin: DNA wrapped around histone proteins; must be decondensed for transcription.

• Epigenetic Tags: Methyl groups condense chromatin (silence genes); acetyl groups open chromatin (activate genes).

• RNA Interference: miRNA binds mRNA, blocking translation or causing degradation.

Cell Differentiation and Development

• Differential Gene Expression: Determines cell fate during development.

• Commitment and Determination: Cells become specialized through regulated gene expression, often locked in by epigenetic changes.

• Apoptosis: Programmed cell death removes unnecessary or misplaced cells.

Scientific Method and Chemistry of Life

Scientific Method

• Theories: Broad, well-supported, testable, and falsifiable explanations.

• Study Design: Eliminate confounding variables for reliable results.

Chemistry of Life

• Polarity: Molecules with many oxygens/nitrogens are polar; carbon/hydrogen-rich molecules are nonpolar.

• Bond Strength: Covalent > Ionic > Hydrogen (in biological systems).

• Hydrophilic vs. Hydrophobic: Polar molecules/ions dissolve in water; nonpolar do not.

• Functional Groups: Modify carbon skeletons, affecting chemical behavior.

• Macromolecules: Large molecules made of monomers (except lipids).

Macromolecules

Carbohydrates

• Composition: C, H, O (1:2:1 ratio); names often end in "-ose".

• Functions: Energy storage (starch, glycogen), structure (cellulose), cell-cell interactions.

• Monosaccharides: Glucose used in cellular respiration.

• Polysaccharides: Starch (plants), glycogen (animals), cellulose (plants; indigestible by humans).

Proteins

• Composition: Chains of amino acids.

• Structure: Sequence determines 3D shape and function.

• Denaturation: Loss of structure (and function) due to heat or chemical changes.

• Enzymes: Proteins that catalyze reactions.

Nucleic Acids

• Composition: Nucleotides (adenine, guanine, cytosine, thymine [DNA], uracil [RNA]).

• Directionality: 5' to 3'; nucleotides added to 3' end.

• Base Pairing: C-G, A-T (DNA), A-U (RNA).

• Functions: DNA stores genetic info; RNA has multiple roles (messenger, structural, catalytic).

• ATP: An activated nucleotide used for energy transfer.

Lipids

• Properties: Hydrophobic; not made of repeating monomers.

• Triglycerides: Nonpolar, long-term energy storage.

• Phospholipids: Amphipathic; form selectively permeable membranes.

• Membrane Permeability: Small/nonpolar molecules cross easily; ions require channels.

Cell Structure and Function

Membranes and Transport

• Diffusion: Movement from high to low concentration.

• Plasma Membrane: Semipermeable; allows selective passage.

• Facilitated Diffusion: Uses protein channels; no energy required.

• Active Transport: Requires ATP to move substances against gradients.

• Electrochemical Gradients: Combination of concentration and charge differences.

Prokaryotes vs. Eukaryotes

• Prokaryotes: No nucleus or membrane-bound organelles; have ribosomes, DNA, plasma membrane.

• Archaea vs. Bacteria: Archaea often live in extreme environments.

• Eukaryotes: Have nucleus, mitochondria, endomembrane system, and other organelles.

Organelles

• Ribosomes: Site of protein synthesis.

• Mitochondria: Site of cellular respiration.

• Chloroplasts: Site of photosynthesis (plants, algae).

• Cytoskeleton: Provides shape and facilitates movement.

• Extracellular Matrix (ECM): Animal cells; Cell Wall: Plant cells.

Viruses and Bacteria

• Viruses: Non-living infectious agents; require host cells to reproduce. Retroviruses use reverse transcriptase to integrate into host DNA.

• Bacteria: Reproduce asexually but can exchange DNA via plasmids, environmental uptake, or viral transfer.

• Antibiotics: Kill or inhibit bacterial growth.

Cell Signaling

• Cell-to-Cell Signaling: Regulates gene expression or activates proteins.

• Signal Transduction: Converts and amplifies signals, often via phosphorylation cascades.

Energy, Enzymes, and Metabolism

• Chemical Energy: Stored in bonds; nonpolar bonds store more energy.

• Electrochemical Gradients: Store potential energy.

• Coupled Reactions: Exergonic reactions drive endergonic ones (e.g., phosphorylation, redox).

• Enzymes: Lower activation energy; affected by temperature and inhibitors.

• Metabolic Pathways: Series of enzyme-catalyzed reactions; often regulated by feedback inhibition.

Cellular Respiration

• Purpose: Convert energy in glucose to ATP.

• Stages:

  1. Glycolysis: Glucose → 2 pyruvate + 2 ATP + 2 NADH.

  2. Citric Acid Cycle: Completes glucose oxidation; produces NADH, FADH2.

  3. Electron Transport Chain: Transfers electrons, creates H+ gradient, drives ATP synthesis (oxidative phosphorylation).

• Fermentation: Anaerobic; less efficient than aerobic respiration.

• Catabolic vs. Anabolic Pathways: Catabolic break down molecules; anabolic build molecules.

Photosynthesis

• Pigments: Absorb specific wavelengths; plants appear green due to reflection of green light.

• Stages:

  1. Light Reactions: Convert light energy to ATP and NADPH.

  2. Calvin Cycle: Uses ATP/NADPH to fix CO2 into carbohydrates (G3P).

• Interdependence: Both stages are linked; Calvin cycle stops without products of light reactions.

Mitosis and Meiosis

Mitosis

• Genome: All genetic material in a cell.

• Chromosome: DNA + proteins; contains many genes.

• Allele: Different versions of a gene.

• Interphase: Cell grows, duplicates DNA.

• Diploid vs. Haploid: Diploid (2n) = two sets of chromosomes; haploid (n) = one set.

• Result: Two genetically identical daughter cells.

• Checkpoints: Ensure accurate division.

Cancer

• Characteristics: Uncontrolled division, loss of differentiation.

• Causes: Mutations/epigenetic changes in proto-oncogenes, tumor suppressor genes, mutator genes.

• Treatment Challenges: Hard to target cancer cells without harming normal cells; many cancer types.

Meiosis and Chromosomal Inheritance

• Aneuploidy: Abnormal chromosome number.

• Meiosis I: Homologous chromosomes separate.

• Meiosis II: Sister chromatids separate.

• Genetic Diversity: Independent assortment, crossing over.

• Nondisjunction: Failure of chromosomes to separate; leads to extra/missing chromosomes.

• Sex Chromosomes: XX (female), XY (male); Y determines maleness.

DNA Technology

• PCR (Polymerase Chain Reaction): Amplifies DNA sequences rapidly.

• CRISPR/Cas9: Precise, efficient gene editing tool.

Genetics Introduction

• Homozygous: Two identical alleles.

• Heterozygous: Two different alleles.

• Genotype: Genetic makeup.

• Phenotype: Observable traits.

Skills for Exam

• Construct and interpret Punnett squares (including codominance, incomplete dominance, sex-linked, and dihybrid crosses).

• Interpret pedigrees to determine inheritance patterns.

• Use codon charts to translate DNA/RNA sequences and predict mutation effects.