IB Biology: Protein Synthesis, Mutations, Evolution, and Homeostasis

RNA Functions and Protein Synthesis Foundations

• Messenger RNA (mRNA): This molecule is complementary to the template or "antisense" DNA strand. It carries the genetic code from the nucleus to the ribosomes.
• Ribosomal RNA (rRNA): Found within ribosomes, it facilitates the decoding of mRNA into sequences of amino acids.
• Transfer RNA (tRNA): This molecule carries specific amino acids to the ribosomes to form polypeptides. It contains an anticodon which is complementary to the mRNA codon.     - tRNA structure: Small, approximately $80$ nucleotides long. It features a point of amino acid attachment at the $3'$ end and an anticodon loop at the opposite end.
• DNA vs. RNA Comparison:     - DNA: Bases are Adenine (A), Thymine (T), Guanine (G), Cytosine (C). It is a double-stranded molecule containing deoxyribose sugar.     - RNA: Bases are Adenine (A), Uracil (U), Guanine (G), Cytosine (C). It is a single-stranded molecule containing ribose sugar.
• Transcription: The production of mRNA using DNA as a template. In prokaryotes, this occurs in the cytoplasm; in eukaryotes, it occurs in the nucleus.     - Initiation: Helicase and RNA polymerase break hydrogen bonds at the start of a gene. This unwinds the two strands and exposes the bases.     - Elongation: RNA polymerase builds an mRNA strand onto the antisense (template) DNA strand matches bases. The DNA behind the polymerase rejoins into a double helix.     - Termination: RNA polymerase reaches a stop codon on the DNA. The pre-mRNA is released. Only specific genes are transcribed into mRNA to prevent wasting energy resources.
• Translation: The process of translating the mRNA sequence into a polypeptide chain.     - Initiation: mRNA attaches to the ribosome at the start codon ($AUG$). A tRNA with the complementary anticodon attached to methionine ($UAC$) binds. All proteins start with methionine because the initiator tRNA binds to $AUG$.     - Elongation: The ribosome moves down the mRNA, bringing two tRNA molecules at a time. The ribosome catalyzes condensation reactions to form peptide bonds between amino acids. tRNA is released as the ribosome progresses.     - Termination: A stop codon is reached. Release factors interact with the peptidyl-tRNA in the P site. The polypeptide is released and the ribosome complex is disassembled and recycled.
• Polysome: A structure where many ribosomes are simultaneously translating a single mRNA molecule, acting like one large moving copy machine.

Regulation of Transcription and mRNA Maturity

• Pre-mRNA Processing (Eukaryotes):     - Exons vs. Introns: Pre-mRNA contains both exons (coding) and introns (non-coding).     - Splicing: Introns are removed by spliceosomes. Exons are ligated together to form mature mRNA.     - Alternative Splicing: Omitting certain exons can result in different versions of proteins with different functions from the same gene.     - Modifications: A $5'$ cap and a poly-A tail are added to the mature mRNA to protect it from degradation.
• Transcriptional Control:     - Promoter Regions: Non-coding segments where RNA polymerase binds to DNA. This is influenced by transcription factors.     - Transcription Factors: A group of proteins that influence expression by encouraging or blocking RNA polymerase binding.     - Enhancer Regions: Activator proteins bind here to aid RNA polymerase binding. They can be located away from the gene.     - Repressor Proteins: These inhibit gene expression by binding to operator sites, preventing RNA polymerase access.
• Lac Operon (Prokaryotes): A cluster of genes ($lacZ, lacY, lacA$) under the control of one regulatory mechanism for lactose metabolism. Bacteria metabolize lactose only if glucose is absent. The $lacI$ gene codes for a repressor that binds the operator when lactose is absent. If lactose is present, it binds to and inhibits the repressor.
• Nucleosome Dynamics: DNA (negative charge) is attracted to histones (positive charge).     - Histone Acetylation/Phosphorylation: Decreases the positive charge, causing DNA to wrap less tightly, making it more accessible to RNA polymerase ($increasing$ expression).     - Methylation: Causes nucleosomes to pack tighter, preventing transcription factor access ($decreasing$ expression).

Epigenetics and mRNA Lifespan

• Epigenetics: Environmental factors that affect gene expression without changing the DNA sequence. Examples include behavior, air pollution ($NO_x$), diet, and temperature.
• Epigenetic Tags: Help regulate gene expression. While most are removed after fertilization, approximately $1\%$ of genes retain tags (imprinted genes).
• mRNA Persistence: mRNA lifespan is regulated to control protein concentrations.     - Poly-A Tail: Increasing maturity and stability.     - Stabilizing Proteins: Prevent nucleases from binding to mRNA.     - Nuclease Abundance: High nuclease concentration leads to faster mRNA degradation.
• Case Study: Monozygotic twins raised similarly have similar epigenetic tags, but environmental differences lead to distinct transcriptomes and proteomes.

Mutations, Genetic Variation, and Biotechnology

• Mutations: Changes in genetic composition. They are the fundamental source of variation. Most are harmful (e.g., cancer, cystic fibrosis), but some offer advantages (e.g., malaria resistance via sickle cell anemia).
• Types of Mutations:     - Point Mutations: Deletion, addition, or replacement of a single nucleotide.     - Substitution: One nucleotide changed. A Synonymous SNP results in the same amino acid. A Non-synonymous SNP changes the amino acid (e.g., sickle cell anemia).     - Frameshift Mutations: Additions or deletions change the entire downstream codon sequence, altering protein structure and function.
• Sickle Cell Anemia: A substitution mutation where Adenine is replaced by Thymine ($GAG \rightarrow GTG$). Glutamic acid is replaced by Valine. This causes mutant hemoglobin to form exposed hydrophobic regions, leading to distorted red blood cell shapes that carry less oxygen.
• Mutagens: Physical agents (UV radiation, X-rays, gamma rays) or chemical agents (mustard gas, nitrous acid, formaldehyde). Deamination involves the loss of an amine group, such as Cytosine turning into Uracil.
• CRISPR-Cas9: A gene-editing technology derived from bacterial immune systems.     - Clustered Regularly Interspaced Short Palindromic Repeats: Bacteria incorporate foreign viral DNA into their own genome as "spacers."     - Mechanism: Single guide RNAs (sgRNAs) lead the Cas9 enzyme to a target site where it creates a double-strand break.     - Applications: Gene knockout (intentionally removing a gene to observe effects), treating genetic disorders, and creating GMOs.

Cell Proliferation and the Cell Cycle

• Cell Proliferation: Essential for growth, tissue repair, and replacement of dead cells. In plants, this occurs in meristems (apical for length, lateral for width).
• Skin Cell Proliferation: Involves clotting, epithelial cell multiplication, and granulation tissue formation.
• Phases of the Cell Cycle:     - Interphase: Divided into $G_1$ (growth, preparation), $S$ (DNA replication), and $G_2$ (final growth and protein synthesis). Some cells (like neurons) enter $G_0$ (cell cycle arrest).     - M Phase: Encompasses Mitosis (nuclear division) and Cytokinesis (cytoplasmic division).
• Cyclins: Proteins that control the progression of the cell cycle to prevent resource overuse.
• Cancer: Caused by uncontrolled cell growth (tumors).     - Proto-oncogenes: Regulate normal division.     - Oncogenes: Mutated forms that lead to cancer.     - Metastasis: Spread of cancer from a primary site to secondary sites.
• Mitotic Index (M.I.): Calculated as $M.I. = \frac{\text{Number of cells in mitosis}}{\text{Total number of cells}} = \frac{P+M+A+T}{\text{Total}}$.

Meiosis and Chromosomal Inheritance

• Meiosis: Two-stage division resulting in four distinct haploid ($n$) daughter cells. In humans, $n=23$ and $2n=46$.     - Meiosis I: Reductive division that halves the chromosome number.     - Meiosis II: Separation of sister chromatids.
• Genetic Variation in Meiosis:     - Crossing Over: Occurs in Prophase I when non-sister chromatids swap sections at the chiasma. The pair of chromosomes is called a bivalent or tetrad.     - Random Assortment: Independent alignment of chromosomes in Metaphase I. For humans, this creates $2^{23}$ ($8,388,608$) possible gamete combinations.
• Nondisjunction: Failure of chromosomes to separate. Leads to aneuploidy (extra or missing chromosomes).     - Trisomy 21: Down Syndrome.     - Trisomy 13: Patau's Syndrome.     - Trisomy 18: Edwards Syndrome.     - XXY: Klinefelter Syndrome.     - Monosomy X: Fragile X / Turner's Syndrome.

Mendelian Inheritance and Phenotypic Variation

• Mendel's Laws:     - Law of Segregation: Maternal and paternal alleles separate during gamete production.     - Law of Independent Assortment: Genes for different traits are sorted independently of each other.
• Variation Types:     - Discrete: Distinct categories (e.g., blood types, widow's peak).     - Continuous/Polygenic: Influenced by multiple genes and the environment, showing a bell curve distribution (e.g., height, skin color).
• ABO Blood Groups: Involves multiple alleles and codominance ($I^A, I^B, i$). Antigens on red blood cells determine the phenotype.
• Sex Linkage: Genes located on the X chromosome (e.g., Haemophilia, red-green color blindness). Recessive traits are more common in males ($XY$) as they lack a second X to mask the allele.
• Phenylketonuria (PKU): A recessive disorder where the PAH enzyme is mutated, leading to a buildup of phenylalanine. Treated with a low-protein diet.
• Linked Genes: Genes located on the same chromosome do not follow the Law of Independent Assortment. The closer they are, the fewer recombinants are produced through crossing over.

Evidence for Evolution and Speciation Dynamics

• Evolution: Heritable changes in a population over time.
• Molecular Evidence: Rate of change in base sequences tracks ancestry. Amino acids change slowest (useful for distant relations); DNA/RNA change faster (useful for close relations).
• Homologous Structures: Similar anatomy but different functions, indicating Divergent Evolution (e.g., the Pentadactyl Limb). Structure includes: $1$ bone (proximal), $2$ bones (distal), a group of wrist/ankle bones (carpals/tarsals), and bones in five digits (phalanges).
• Analogous Structures: Different origins but similar functions, indicating Convergent Evolution (e.g., wings of insects and birds).
• Speciation Models:     - Gradualism: Slow, steady change with intermediate forms.     - Punctuated Equilibrium: Long periods of stasis followed by sudden changes.
• Reproductive Isolation:     - Allopatric: Caused by geographical barriers (e.g., Chimpanzees and Bonobos separated by the Congo River).     - Sympatric: Occurs in the same area due to Temporal (timing) or Behavioral (courtship) isolation.
• Adaptive Radiation: Rapid evolution into different niches (e.g., Galapagos finches' beaks adapted to food sources).
• Polyploidy: Abrupt speciation through having extra sets of chromosomes (common in plants). Allotetraploidy occurs after hybridization followed by doubling.

Natural Selection and Population Genetics

• VISTA: Variation, Inheritance, Survival/Selection, Time, Adaptations.
• Selection Pressures: Factors affecting survival.     - Density-Dependent: Predation, nutrient availability, disease.     - Density-Independent: Temperature, weather, natural disasters.
• Adaptation Types: Structural (body form), Behavioral (activity patterns), and Physiological (internal organ variation).
• Sexual Selection: Evolution of exaggerated traits to attract mates (e.g., John Endler’s guppies where bright color increases mating but also predation risk).
• Hardy-Weinberg Equation: Used to calculate allele and genotype frequencies ($p+q=1$ and $p^2+2pq+q^2=1$). Conditions include: no selection, no mutation, random mating, no gene flow, and no genetic drift.
• Selection Types:     - Stabilizing: Favors intermediate variants; removes extremes.     - Disruptive: Favors both extremes; removes intermediates; can lead to speciation (bimodal).     - Directional: Favors one extreme; shifts the mean.

Biodiversity Crisis and Conservation Strategies

• Biodiversity: Variety of ecosystems, species, and genetic pools. Estimated $2\text{-}10$ million eukaryotes exist.
• Anthropogenic Extinction Causes: Overharvesting, habitat destruction (agriculture/urbanization), invasive species, pollution, and climate change.
• Simpson’s Reciprocal Index: Quantifies biodiversity. $D = \frac{N(N-1)}{\sum n(n-1)}$ where $N$ is the total number of individuals and $n$ is the total of a specific species.
• Conservation Priorities: Priority given to species that are Evolutionarily Distinct and Globally Endangered (EDGE).
• Conservation Methods:     - In situ: Conservation within natural habitats (e.g., National Parks).     - Ex situ: Conservation outside the natural habitat (e.g., zoos, botanical gardens).

Integration of Human Body Systems and Homeostasis

• Emergent Properties: Characteristics that arise when system parts sum to a whole (e.g., life in cells, heart tissue contraction).
• Control Systems:     - Nervous System: Uses electrochemical signals (millisecond response).     - Endocrine System: Uses hormones secreted from glands into the bloodstream (longer-lasting response).
• Homeostasis: Maintenance of an equilibrium in the internal environment relative to tolerance limits.     - Negative Feedback: Reverses a change (e.g., blood glucose control).     - Positive Feedback: Amplifies a change (e.g., childbirth via oxytocin, blood clotting).
• Blood Glucose Control: Monitored by the hypothalamus and regulated by the pancreas (beta cells release Insulin to lower glucose via glycogen synthesis; alpha cells release Glucagon to raise glucose via glycogenolysis).
• Diabetes:     - Type 1: Early onset; beta cell destruction; treated with insulin injections.     - Type 2: Late onset; down-regulation of insulin receptors; treated with lifestyle changes.

Endocrinology and Thermoregulation

• Thermoregulation: Hypothalamus acts as a control center.     - Heat Generation: TSH triggers the release of Thyroxin from the thyroid, increasing the basal metabolic rate. Shivering and Brown Adipose Tissue (using UCP1 to convert protons into heat in the Electron Transport Chain) generate heat.     - Cooling/Heating Mechanisms: Vasoconstriction (narrowing vessels) for cold; Vasodilation (widening) and sweating for heat. Piloerection (hairs sticking up) traps air for insulation.
• Circadian Rhythms: Controlled by Melatonin from the pineal gland. Light-sensitive retina tissue sends signals to the Suprachiasmatic Nucleus (SCN). Melatonin is high in darkness (promoting sleep in diurnals) and inhibited by daylight (triggering serotonin).
• Epinephrine (Adrenaline): Fight-or-flight hormone from the adrenal glands. Increases heart rate, blood pressure, and breathing while dilating pupils.
• Cardiovascular Sense:     - Baroreceptors: Stretch-sensitive receptors in the carotid sinuses and aortic arch that respond to blood pressure changes.     - Chemoreceptors: Respond to changes in $CO_2$ (hypercapnia) or $O_2$ (hypoxia) to regulate heart rate via the Medulla Oblongata.