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% miko:title: Biology
% miko:summary: A concise guide to biology.
% miko:category: biology
% miko:type: complete
% miko:origin: ai
% miko:tags: biology
% miko:difficulty: undergrad
% miko:keywords: biology

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\title{Complete Biology}
\author{Miko-pedia AI}
\date{\today}

\begin{document}
\maketitle
\tableofcontents

\textbf{Overview.} This complete note provides an undergraduate-level review of biology, from the molecular chemistry of life and cellular structure through genetics, evolution, organismal physiology, ecology, and experimental methods. Each section integrates essential vocabulary, key mechanisms, quantitative tools, and canonical experiments. The progression mirrors the logical structure of the discipline: chemistry $\rightarrow$ cell $\rightarrow$ genetics $\rightarrow$ evolution $\rightarrow$ diversity $\rightarrow$ organism $\rightarrow$ ecology. Use this overview to identify gaps and navigate directly to the topics you need to review.

\section{Unifying Principles of Life: Cells, Information, Energy, and Evolution}
\subsection{Core ideas}
All living organisms share a set of unifying properties: they are composed of cells, process hereditary information encoded in DNA, extract and use energy from their environment, and evolve through natural selection.

The \textbf{cell theory} states that (1) all living things are composed of one or more cells, (2) the cell is the basic structural and functional unit of life, and (3) all cells arise from pre-existing cells. The third tenet was famously verified by \textbf{Louis Pasteur's swan-neck flask experiment} (1859), which disproved spontaneous generation. Cells are classified as \textbf{prokaryotic} (lacking a membrane-bound nucleus; bacteria and archaea) or \textbf{eukaryotic} (possessing a nucleus and membrane-bound organelles; protists, fungi, plants, animals). Despite their differences, all cells share a plasma membrane, cytoplasm, ribosomes, and a DNA genome.

The \textbf{central dogma of molecular biology} (Crick, 1958) describes the flow of genetic information: DNA $\rightarrow$ RNA $\rightarrow$ Protein. DNA stores information; transcription produces messenger RNA (mRNA); translation uses mRNA to assemble polypeptides. This information is heritable and subject to mutation, providing the raw material for evolution.

Life requires a constant input of energy. \textbf{Metabolism} encompasses all chemical reactions in an organism. \textbf{Catabolism} breaks down molecules to release energy; \textbf{anabolism} uses energy to build molecules. The universal energy currency is \textbf{ATP} (adenosine triphosphate). The \textbf{first law of thermodynamics} (energy conservation) and the \textbf{second law} (entropy, or disorder, always increases) govern all biological processes. Living systems maintain \textbf{homeostasis} -- internal stability -- by expending energy to oppose entropy.

\textbf{Evolution} by natural selection is the central organizing principle of biology. Darwin and Wallace (1858) proposed that individuals with heritable traits better suited to their environment survive and reproduce more successfully, causing populations to change over generations. The four postulates are: (1) variation exists among individuals, (2) variation is heritable, (3) more offspring are produced than can survive, (4) survival and reproduction are non-random.

For review, be able to: list the properties of life; state the cell theory; explain the central dogma; define metabolism, catabolism, anabolism, and ATP; interpret the two laws of thermodynamics in biological context; describe natural selection's four postulates; distinguish prokaryotes from eukaryotes; explain why entropy makes energy input necessary.

\paragraph{Section summary}
Life is defined by cells, genetic information, energy harvesting, and evolution. The cell theory, central dogma, metabolism, thermodynamics, and natural selection form the conceptual foundation. All biological complexity rests on these five pillars.

\section{The Chemistry of Life: Water, Carbon, and Macromolecules}
\subsection{Core ideas}
Life is carbon-based and operates in an aqueous medium. \textbf{Water} is polar, forms hydrogen bonds, and has emergent properties vital for life: high specific heat (temperature buffering), high heat of vaporization, cohesion (molecules sticking together), adhesion (sticking to surfaces), and expansion upon freezing. These properties arise from extensive hydrogen bonding. Water is the universal solvent in biology, dissolving polar and ionic compounds (hydrophilic) while excluding non-polar ones (hydrophobic).

\textbf{Carbon} forms four covalent bonds, allowing an immense diversity of organic molecules. \textbf{Functional groups} (hydroxyl, carbonyl, carboxyl, amino, sulfhydryl, phosphate, methyl) confer distinct chemical properties. \textbf{Isomers} (structural, geometric/cis-trans, enantiomers) add further complexity. Enantiomers are chiral, mirror-image molecules; biological systems typically use only one stereoisomer (e.g., L-amino acids, D-sugars).

The four major classes of \textbf{macromolecules} are carbohydrates, lipids, proteins, and nucleic acids. Most are polymers assembled from monomers via \textbf{dehydration synthesis} (condensation releasing water) and broken down by \textbf{hydrolysis} (addition of water).

\begin{itemize}
  \item \textbf{Carbohydrates:} Composed of monosaccharides ($\text{C}_n\text{H}_{2n}\text{O}_n$). Glucose ($\text{C}_6\text{H}_{12}\text{O}_6$) is the central energy source. Disaccharides (sucrose, lactose) form via glycosidic linkages. Polysaccharides (starch, glycogen for energy; cellulose, chitin for structure). Cellulose, a $\beta(1\rightarrow4)$ polymer of glucose, is indigestible by most animals but essential as dietary fiber.
  \item \textbf{Lipids:} Hydrophobic molecules including fats (triacylglycerols), phospholipids, and steroids. Fats store energy ($\sim 37\ \text{kJ/g}$, twice that of carbohydrates). Phospholipids are amphipathic (hydrophilic head, hydrophobic tail) and spontaneously form bilayers -- the basis of all membranes. Steroids (e.g., cholesterol, testosterone) have a rigid four-ring carbon skeleton.
  \item \textbf{Proteins:} Polymers of amino acids joined by peptide bonds. There are 20 standard amino acids with varied side chains (R-groups: non-polar, polar uncharged, charged). Protein structure has four levels: primary (linear amino acid sequence), secondary ($\alpha$-helices and $\beta$-sheets stabilized by backbone hydrogen bonds), tertiary (overall 3D folding stabilized by R-group interactions), and quaternary (multi-subunit assembly, e.g., hemoglobin). \textbf{Chaperonins} assist in proper folding. Function is determined by structure; denaturation (unfolding) destroys function.
  \item \textbf{Nucleic acids:} DNA and RNA are polymers of nucleotides. Each nucleotide has a phosphate, a pentose sugar (deoxyribose in DNA, ribose in RNA), and a nitrogenous base (A, G, C, T in DNA; A, G, C, U in RNA). DNA is double-stranded with antiparallel strands held by complementary base pairing (2 hydrogen bonds for A--T, 3 for G--C). RNA is typically single-stranded but can fold into complex 3D shapes.
\end{itemize}

For review, be able to: explain water's emergent properties; identify functional groups; name the four macromolecule classes; describe polymerization by dehydration synthesis; distinguish $\alpha$ and $\beta$ glucose linkages; explain the four levels of protein structure; draw a nucleotide; state Chargaff's rules (base pairing).

\paragraph{Section summary}
Water's hydrogen-bonding chemistry makes it the ideal solvent for life. Carbon's tetravalency enables the rich diversity of organic molecules. Four macromolecule classes -- carbohydrates, lipids, proteins, and nucleic acids -- are built from monomers and serve as structural, energetic, informational, and catalytic components of life.

\section{The Cell: Membranes, Organelles, Metabolism, and Signaling}
\subsection{Core ideas}
The \textbf{plasma membrane} is a phospholipid bilayer with embedded proteins. The \textbf{fluid mosaic model} (Singer and Nicolson, 1972) describes membranes as dynamic structures where lipids and proteins diffuse laterally. Membrane proteins function as transporters, enzymes, receptors, and anchors.

Transport across membranes occurs by \textbf{passive transport} (diffusion, facilitated diffusion via channel or carrier proteins) requiring no energy, and \textbf{active transport} (e.g., the $\text{Na}^+$/$\text{K}^+$ pump, endocytosis, exocytosis) requiring ATP to move substances against their gradient. \textbf{Osmosis} is the diffusion of water across a selectively permeable membrane via aquaporins. Tonicity (hypertonic, hypotonic, isotonic) describes the effect on cell volume.

\textbf{Organelles} compartmentalize eukaryotic cells:
\begin{itemize}
  \item \textbf{Nucleus:} Contains DNA; enclosed by a double membrane (nuclear envelope) with nuclear pores. The nucleolus produces ribosomal RNA.
  \item \textbf{Ribosomes:} Sites of protein synthesis (free in cytoplasm or bound to rough ER).
  \item \textbf{Endoplasmic reticulum (ER):} Rough ER (studded with ribosomes) processes secretory proteins; smooth ER synthesizes lipids, metabolizes carbohydrates, and detoxifies.
  \item \textbf{Golgi apparatus:} Modifies, sorts, and packages proteins for transport.
  \item \textbf{Lysosomes:} Contain hydrolytic enzymes for intracellular digestion (autophagy, phagocytosis).
  \item \textbf{Mitochondria:} Sites of cellular respiration; contain their own DNA and double membranes. The inner membrane folds into cristae to increase surface area.
  \item \textbf{Chloroplasts (plants):} Sites of photosynthesis; contain thylakoid membranes stacked into grana.
  \item \textbf{Peroxisomes:} Break down fatty acids and detoxify hydrogen peroxide.
  \item \textbf{Cytoskeleton:} Network of microfilaments (actin), intermediate filaments, and microtubules (tubulin) providing structure, motility, and intracellular transport.
\end{itemize}

\textbf{Cell signaling} involves reception (ligand binds receptor), transduction (signal relay via phosphorylation cascades, second messengers like cAMP, $\text{Ca}^{2+}$, IP$_3$), and response (gene expression, metabolism change). \textbf{Second messengers} are small, non-protein intracellular signaling molecules. Experimental evidence by \textbf{Earl Sutherland} (1956) showed that epinephrine triggers glycogen breakdown via cAMP acting as a second messenger. Major receptor types: G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and ion channel receptors.

For review, be able to: describe the fluid mosaic model; compare passive and active transport; explain osmosis and tonicity; list organelle functions; outline the endomembrane system; trace a signal from receptor to response; distinguish paracrine, synaptic, and endocrine signaling.

\paragraph{Section summary}
The plasma membrane controls exchange between cell and environment. Eukaryotic organelles compartmentalize functions from energy production to protein trafficking. Cell signaling networks allow cells to sense and respond to their surroundings. The endosymbiotic theory explains the origins of mitochondria and chloroplasts.

\section{Genetic Information: DNA, RNA, and Proteins}
\subsection{Core ideas}
\textbf{Overview.} The central dogma dictates that DNA stores information, which is transcribed into RNA and translated into functional proteins. This requires precise replication mechanisms and complex regulatory networks.

\textbf{DNA replication} is semiconservative: each daughter molecule contains one old and one new strand. The \textbf{Meselson-Stahl experiment} (1958) proved this using $^{15}\text{N}$ density gradient ultracentrifugation. Key enzymes act sequentially: \textbf{helicase} unwinds the double helix; \textbf{single-strand binding proteins (SSBs)} stabilize the unwound DNA; \textbf{topoisomerase} relieves supercoiling; \textbf{primase} synthesizes a short RNA primer; \textbf{DNA polymerase III} extends the new strand $5'\rightarrow3'$; \textbf{DNA polymerase I} replaces RNA primers with DNA; and \textbf{DNA ligase} joins discontinuous \textbf{Okazaki fragments} on the lagging strand.

\textbf{Transcription} (DNA $\rightarrow$ RNA) relies on \textbf{RNA polymerase}, which binds to a \textbf{promoter} (a specific DNA sequence initiating transcription, e.g., TATA box). In eukaryotes, immature pre-mRNA requires processing: addition of a $5'$ cap (for ribosome binding), a $3'$ poly-A tail (for stability), and \textbf{splicing} (removal of non-coding \textbf{introns} and joining of coding \textbf{exons} by the \textbf{spliceosome}). \textbf{Alternative splicing} allows one gene to produce multiple protein variants.

\textbf{Translation} (RNA $\rightarrow$ Protein) occurs on ribosomes in three stages: initiation (requires initiation factors), elongation, and termination. The \textbf{genetic code} maps mRNA \textbf{codons} (triplets) to amino acids; it is degenerate (multiple codons per amino acid) and nearly universal. Transfer RNA (\textbf{tRNA}) carries an \textbf{anticodon} and delivers the amino acid. The ribosome acts as a \textbf{ribozyme} (an RNA enzyme), catalyzing peptide bonds as tRNAs transit its A (aminoacyl), P (peptidyl), and E (exit) sites.

\textbf{Gene regulation} ensures proteins are made only when needed. Prokaryotes use \textbf{operons}---a functioning unit of DNA containing a cluster of genes under the control of a single promoter. For example, the \textit{lac} operon includes an \textbf{operator} (binding site for a repressor); lactose acts as an \textbf{inducer}, binding the repressor to allow transcription. Eukaryotic regulation uses \textbf{transcription factors} binding \textbf{enhancers}. \textbf{Epigenetics} involves heritable traits not caused by DNA sequence changes, such as \textbf{DNA methylation} (represses) and \textbf{histone acetylation} (relaxes chromatin to activate).

\textbf{Experimental evidence:} Griffith (1928) observed that a "transforming principle" could make harmless bacteria virulent. Avery, MacLeod, and McCarty (1944) identified this as DNA. Hershey and Chase (1952) proved DNA is the genetic material by showing that only $^{32}\text{P}$-labeled phage DNA (not $^{35}\text{S}$-labeled protein) entered host bacteria. The triplet nature of the genetic code was confirmed by the \textbf{Crick-Brenner experiment} (1961) using frameshift mutations.

For review, be able to: diagram the replication fork; explain semiconservative replication; describe RNA processing steps; define codon, anticodon, and operon; explain the \textit{lac} operon mechanism; contrast prokaryotic and eukaryotic gene regulation.

\paragraph{Section summary}
Genetic information flows from DNA to RNA to protein. DNA replicates semiconservatively and is transcribed into RNA, which undergoes processing in eukaryotes. Ribosomes translate mRNA into proteins using the genetic code. Gene expression is tightly controlled via operons in prokaryotes and epigenetic/transcriptional mechanisms in eukaryotes.

\section{Genetics and Genomes: From Mendel to CRISPR}
\subsection{Core ideas}
\textbf{Mendelian genetics} rests on the work of Gregor Mendel (1865) on pea plants. Key principles:
\begin{itemize}
  \item \textbf{Law of Segregation:} Each individual has two \textbf{alleles} (variant forms of a gene located at a specific locus) for each gene; they segregate during gamete formation.
  \item \textbf{Law of Independent Assortment:} Genes on different chromosomes assort independently during meiosis.
\end{itemize}
Mendel's monohybrid crosses yielded 3:1 \textbf{phenotypic} (observable traits) ratios in the F$_2$ generation from heterozygotes. A \textbf{Punnett square} predicts offspring \textbf{genotypes} (genetic makeup). Dominance relationships: complete, incomplete (pink snapdragons from red $\times$ white), and codominance (ABO blood type, where both alleles are expressed).

\textbf{Extensions to Mendel:} \textbf{Pleiotropy} (one gene affects multiple traits, e.g., Marfan syndrome). \textbf{Epistasis} (one gene masks another, e.g., coat color in Labrador retrievers). \textbf{Polygenic inheritance} (multiple genes affect one trait, e.g., human height, skin color). \textbf{Linkage} (genes physically close on the same chromosome do not assort independently). Recombination frequency (crossing over) maps gene distance: 1 map unit (centimorgan) = 1\% recombination.

\textbf{Sex determination} varies: XY system (mammals), ZW system (birds), XO system (some insects), haplodiploidy (bees). Sex-linked traits (e.g., hemophilia, color blindness) show distinctive inheritance patterns, mostly affecting heterogametic males (XY).

\textbf{Genomics} studies entire genomes. The human genome ($\sim 3\times 10^9$ bp) was sequenced (2001). Only $\sim 1.5\%$ codes for proteins; the rest includes non-coding RNA genes, regulatory sequences, introns, and repetitive DNA (transposons, retrotransposons). Comparative genomics reveals evolutionary relationships.

\textbf{Modern tools:}
\begin{itemize}
  \item \textbf{PCR} (polymerase chain reaction): Amplifies specific DNA sequences in cycles of denaturation, annealing, and extension using thermostable \textit{Taq} DNA polymerase.
  \item \textbf{DNA sequencing:} Sanger (dideoxy chain-termination), next-generation (massively parallel).
  \item \textbf{CRISPR-Cas9:} A genome-editing tool derived from bacterial adaptive immunity. Guide RNA (gRNA) directs the Cas9 \textbf{endonuclease} to a specific DNA sequence adjacent to a PAM motif, creating a targeted double-strand break. Repair via non-homologous end joining (NHEJ) or homology-directed repair (HDR) enables precise gene knockout, insertion, or correction.
  \item \textbf{Gene cloning:} Inserting a foreign gene into a plasmid vector using restriction enzymes and transforming bacteria.
  \item \textbf{Gel electrophoresis:} Separates DNA fragments by size using an electric field.
\end{itemize}

For review, be able to: solve monohybrid and dihybrid cross problems; explain Mendel's laws; distinguish dominance types; identify epistasis and pleiotropy; calculate recombination frequency; describe PCR steps (denature, anneal, extend); outline CRISPR-Cas9 mechanism; discuss ethical issues in genetic engineering.

\paragraph{Section summary}
Mendel's laws describe the transmission of discrete hereditary factors (genes). Extensions include epistasis, pleiotropy, linkage, and polygenic traits. Modern genomics and tools like PCR, sequencing, and CRISPR-Cas9 enable precise analysis and manipulation of genomes.

\section{Biochemistry: Enzymes, Metabolism, and Energy}
\subsection{Core ideas}
\textbf{Overview.} Biochemistry focuses on the chemical processes that drive life. At the core are enzymes, which catalyze reactions, and metabolic pathways, which systematically harvest energy from nutrients (respiration) or capture it from sunlight (photosynthesis).

\textbf{Enzymes} are biological catalysts (primarily proteins, though some RNA \textbf{ribozymes} exist). They accelerate reactions by lowering the \textbf{activation energy} ($E_a$)—stabilizing the transition state required to start a reaction—without altering the overall free energy change ($\Delta G$) or being consumed. The enzyme's \textbf{active site} (a specific structural pocket) conforms to the \textbf{substrate} (reactant) via the \textbf{induced-fit model}, optimizing catalysis.

Enzyme kinetics (e.g., Michaelis--Menten) describes how reaction rates depend on substrate concentration, temperature, and pH. \textbf{Cofactors} (inorganic ions like $\text{Zn}^{2+}$) and \textbf{coenzymes} (organic molecules derived from vitamins, like $\text{NAD}^+$) aid function. Enzyme regulation includes:
\begin{itemize}
  \item \textbf{Competitive inhibition:} An inhibitor blocks the active site directly; can be outcompeted by adding more substrate.
  \item \textbf{Non-competitive inhibition:} An inhibitor binds an \textbf{allosteric site} (a distinct regulatory site), changing the enzyme's shape and reducing its maximum rate ($V_{\max}$).
  \item \textbf{Feedback inhibition:} The final product of a metabolic pathway allosterically inhibits an early committed step (e.g., ATP inhibits \textbf{phosphofructokinase-1} (PFK-1) in glycolysis, while AMP activates it), maintaining homeostasis.
\end{itemize}

\textbf{Cellular respiration} is the controlled oxidation of glucose to yield ATP:
\begin{enumerate}
  \item \textbf{Glycolysis} (cytosol): A 10-step anaerobic pathway (the Embden-Meyerhof-Parnas pathway, experimentally elucidated using yeast extracts) splitting glucose (6C) into two pyruvate (3C) molecules. Yields a net 2 ATP and 2 NADH. Key rate-limiting enzyme: PFK-1.
  \item \textbf{Pyruvate oxidation} (mitochondrial matrix): Pyruvate is decarboxylated into acetyl-CoA (2C), releasing CO$_2$ and generating NADH.
  \item \textbf{Citric acid cycle (Krebs cycle)} (matrix): Acetyl-CoA combines with oxaloacetate (4C) to form citrate (6C). Through a cycle of oxidations, it yields 2 CO$_2$, 3 NADH, 1 $\text{FADH}_2$, and 1 GTP/ATP per turn.
  \item \textbf{Oxidative phosphorylation} (inner mitochondrial membrane): The \textbf{electron transport chain (ETC)} passes electrons from NADH/$\text{FADH}_2$ through complexes I--IV, releasing energy used to pump protons ($\text{H}^+$) into the intermembrane space. This creates an electrochemical gradient (proton-motive force). \textbf{Chemiosmosis} occurs as protons flow back through \textbf{ATP synthase}, driving the synthesis of $\sim 26$--28 ATP. O$_2$ is the final electron acceptor, forming $\text{H}_2\text{O}$. Total yield is $\sim 30$--32 ATP per glucose.
\end{enumerate}

\textbf{Photosynthesis} converts light energy into chemical energy:
\begin{enumerate}
  \item \textbf{Light reactions} (thylakoid membrane): Chlorophyll absorbs photons, exciting electrons. Water is split (\textbf{photolysis}) to replace these electrons, releasing O$_2$. Electrons pass through Photosystem II, the cytochrome complex, and Photosystem I, pumping protons and generating ATP (via photophosphorylation) and reducing $\text{NADP}^+$ to NADPH.
  \item \textbf{Calvin cycle} (stroma): The enzyme \textbf{RuBisCO} fixes CO$_2$ into a 5-carbon sugar (RuBP), forming 3-phosphoglycerate. Using ATP and NADPH from the light reactions, this is reduced to glyceraldehyde-3-phosphate (G3P), which exits the cycle to form glucose.
\end{enumerate}

For review, be able to: explain how enzymes lower activation energy; differentiate competitive, non-competitive, and allosteric inhibition; trace the flow of carbon and electrons through glycolysis, the Krebs cycle, and the ETC; describe the proton-motive force and chemiosmosis; outline the light-dependent reactions and Calvin cycle; define RuBisCO.

\paragraph{Section summary}
Enzymes regulate the metabolic pathways of the cell. Cellular respiration sequentially extracts energy from glucose via glycolysis, the citric acid cycle, and oxidative phosphorylation, relying on chemiosmosis for maximum ATP yield. Conversely, photosynthesis uses light to drive electron transport, producing ATP and NADPH to power carbon fixation in the Calvin cycle.

\section{Evolution: Natural Selection, Populations, Speciation, and Phylogeny}
\subsection{Core ideas}
\textbf{Natural selection} requires heritable variation, overproduction of offspring, and differential reproductive success. \textbf{Darwin's finches} (beak size dynamically correlates with seed availability due to drought, as documented by Grant and Grant) provide a classic example. Types of selection include: \textbf{directional} (one extreme phenotype favored, shifting the population mean), \textbf{stabilizing} (intermediate phenotype favored, reducing variance), and \textbf{disruptive} (both extremes favored, potentially leading to sympatric speciation). \textbf{Sexual selection} favors traits that increase mating success, often leading to sexual dimorphism.

\textbf{Microevolution} refers to changes in allele frequencies within a single population. \textbf{Population genetics} studies these changes over time. The \textbf{Hardy--Weinberg principle} acts as a null model describing a non-evolving population where allele frequencies remain constant. It relies on five conditions: no mutation, random mating, no natural selection, extremely large population size, and no gene flow. The Hardy-Weinberg equations are $p + q = 1$ (allele frequencies) and $p^2 + 2pq + q^2 = 1$ (genotype frequencies). \textbf{Genetic drift} is the random fluctuation of allele frequencies, heavily impacting small populations via the \textbf{bottleneck effect} or \textbf{founder effect}. \textbf{Neutral theory of molecular evolution} (Motoo Kimura, 1968) posits that at the molecular level, most evolutionary changes and variation within and between species are not caused by natural selection but by genetic drift of neutral mutant alleles.

\textbf{Macroevolution} and \textbf{Speciation} describe large-scale evolutionary patterns, including the origin of new taxonomic groups. The \textbf{Biological species concept} (Ernst Mayr) defines species as groups of interbreeding natural populations that are reproductively isolated. \textbf{Allopatric speciation} occurs via geographic isolation, while \textbf{sympatric speciation} occurs without it, often through polyploidy or sexual selection. The tempo of speciation is debated: \textbf{Phyletic gradualism} suggests slow, steady change, whereas \textbf{punctuated equilibrium} (Eldredge and Gould, 1972) proposes that species remain stable for long periods (stasis), interrupted by brief periods of rapid change during speciation events. \textbf{Adaptive radiation} is the rapid evolution of diversely adapted species from a common ancestor (e.g., Hawaiian honeycreepers). \textbf{Reproductive isolation} maintains boundaries: \textbf{pre-zygotic} (habitat, temporal, behavioral, mechanical, gametic isolation) and \textbf{post-zygotic} (hybrid inviability, sterility, or breakdown).

\textbf{Phylogeny} maps the evolutionary history of a group, depicted as a \textbf{cladogram} or \textbf{phylogenetic tree}. Branches denote lineages; nodes represent the most recent common ancestor. \textbf{Monophyletic} groups (clades) contain an ancestor and all its descendants. \textbf{Paraphyletic} groups contain an ancestor and some descendants. \textbf{Polyphyletic} groups lack a recent common ancestor. Trees are constructed using \textbf{molecular homology} and the principle of \textbf{maximum parsimony} (fewest evolutionary events).

\textbf{Evidence for evolution} includes the fossil record (transitional forms like \textit{Tiktaalik}), \textbf{homologous structures} (shared ancestry, e.g., tetrapod limbs), \textbf{vestigial structures} (remnants like whale pelvic bones), and direct observation (antibiotic resistance). \textbf{Convergent evolution} leads to \textbf{analogous structures} (similar function but different ancestry, e.g., bird and insect wings).

For review, be able to: calculate allele frequencies using HW equations; explain Kimura's neutral theory vs. Darwinian selection; distinguish punctuated equilibrium from gradualism; read a phylogenetic tree; differentiate homologous vs. analogous structures.

\paragraph{Section summary}
Evolution is the change in allele frequencies across generations, driven by natural selection, genetic drift (including neutral theory), and gene flow. Speciation creates biodiversity via allopatric or sympatric mechanisms, often following patterns like punctuated equilibrium. Phylogenetic trees diagram historical relationships based on homology and parsimony. Extensive evidence from fossils to genomes supports evolutionary theory.

\section{Diversity of Life: Microbes, Plants, Fungi, and Animals}
\subsection{Core ideas}
The \textbf{three domains} of life (proposed by Carl Woese, 1977, based on highly conserved 16S/18S rRNA sequences) are \textbf{Bacteria}, \textbf{Archaea}, and \textbf{Eukarya}. Bacteria and Archaea are prokaryotic; Eukarya features membrane-bound organelles. The \textbf{endosymbiotic theory} (Lynn Margulis) posits that mitochondria and chloroplasts originated as engulfed aerobic and photosynthetic prokaryotes, evidenced by their double membranes, independent circular DNA, and prokaryotic-like ribosomes.

\textbf{Bacteria} and \textbf{Archaea} are unicellular prokaryotes. Bacteria are classified as \textbf{Gram-positive} (thick peptidoglycan) or \textbf{Gram-negative} (thin peptidoglycan and outer membrane). They achieve diversity via \textbf{horizontal gene transfer} (transformation, conjugation, transduction). Archaea are often \textbf{extremophiles} (halophiles, thermophiles, methanogens) with distinct membrane lipids. \textbf{Protists} are a vast, paraphyletic grouping of eukaryotes that don't fit elsewhere (e.g., \textit{Amoeba}, \textit{Plasmodium}).

\textbf{Fungi} are eukaryotic \textbf{absorptive heterotrophs} with \textbf{chitin} cell walls. They form networks of \textbf{hyphae} (mycelium). Key phyla include Zygomycota, Ascomycota (yeasts, morels), and Basidiomycota (mushrooms). Mutualistic roles include \textbf{mycorrhizae} (with plant roots) and \textbf{lichens} (with algae/cyanobacteria).

\textbf{Plants} are multicellular eukaryotic autotrophs with cellulose walls, featuring \textbf{alternation of generations} (haploid gametophyte and diploid sporophyte).
\begin{itemize}
  \item \textbf{Bryophytes} (mosses): Non-vascular, gametophyte-dominant.
  \item \textbf{Seedless Vascular Plants} (ferns): Evolution of \textbf{xylem} and \textbf{phloem}; sporophyte-dominant.
  \item \textbf{Gymnosperms} (conifers): Evolution of \textbf{seeds} and pollen.
  \item \textbf{Angiosperms} (flowering plants): Flowers for pollination and fruits for seed dispersal. Divided into monocots and eudicots.
\end{itemize}

\textbf{Animals} are multicellular, eukaryotic, ingestive heterotrophs. Body plans vary by \textbf{symmetry} (radial vs. bilateral), \textbf{body cavities} (acoelomate, pseudocoelomate, coelomate), and \textbf{development} (\textbf{protostomes} vs. \textbf{deuterostomes}).
\begin{itemize}
  \item \textbf{Arthropoda} (insects, crustaceans): The most successful animal phylum, attributed to their \textbf{segmented body}, \textbf{hard exoskeleton} (chitin), and \textbf{jointed appendages}, allowing for incredible niche specialization.
  \item \textbf{Chordata}: Defined by four hallmark traits present at some stage of development: 1) a \textbf{notochord} (flexible support rod), 2) a \textbf{dorsal hollow nerve cord}, 3) \textbf{pharyngeal slits} (for filter feeding or gas exchange), and 4) a \textbf{post-anal tail}. Includes fish, amphibians, reptiles, birds, and mammals.
  \item Other Phyla: \textbf{Porifera} (sponges, no true tissues), \textbf{Cnidaria} (jellies, radial symmetry), \textbf{Mollusca} (snails, octopuses), \textbf{Echinodermata} (starfish, deuterostomes).
\end{itemize}

For review, be able to: compare the three domains; identify evidence for endosymbiosis; explain alternation of generations; list the four hallmark chordate traits; explain why arthropods are so diverse.

\paragraph{Section summary}
Life's diversity is organized into three domains, with endosymbiosis driving eukaryotic complexity. Fungi are decomposers with chitin walls; plants adapted to land via vascular tissue and seeds; and animals exhibit diverse body plans, with arthropods and chordates representing the peak of structural complexity and ecological dominance.

\section{The Organism: Development, Physiology, Nervous System, Immunity, and Reproduction}
\subsection{Core ideas}
\textbf{Development:} Involves \textbf{cleavage} (rapid mitosis), \textbf{gastrulation} (forming ectoderm, mesoderm, and endoderm), and \textbf{organogenesis}. \textbf{Hox genes} masterfully regulate the body plan.

\textbf{Physiology} maintains \textbf{homeostasis} via feedback loops.
\begin{itemize}
  \item \textbf{Gas Exchange}: Hemoglobin transports O$_2$ in blood. The \textbf{Bohr effect} describes how increased CO$_2$ and decreased pH (acidic conditions typical of active tissues) lower hemoglobin's affinity for O$_2$, promoting its release where needed.
  \item \textbf{Muscle Contraction}: The \textbf{sliding filament model} explains how muscles contract. Ca$^{2+}$ binds to troponin, moving tropomyosin to expose myosin-binding sites on actin. Myosin heads then bind, undergo a power stroke fueled by ATP, and slide actin filaments toward the center of the sarcomere.
  \item \textbf{Excretion}: The \textbf{nephron} is the kidney's functional unit. It filters blood at the \textbf{glomerulus}, reabsorbs water and solutes in the \textbf{proximal tubule}, and concentrates urine using a \textbf{countercurrent multiplier} system in the \textbf{loop of Henle}.
\end{itemize}

\textbf{Nervous system:} Neurons use \textbf{action potentials} for signaling.
\begin{enumerate}
  \item \textbf{Resting}: $-70$ mV maintained by Na$^+$/K$^+$ pumps.
  \item \textbf{Depolarization}: Threshold reached; voltage-gated Na$^+$ channels open; membrane potential spikes.
  \item \textbf{Repolarization}: Na$^+$ channels close, K$^+$ channels open; K$^+$ exits the cell.
  \item \textbf{Hyperpolarization}: Excess K$^+$ exit; refractory period prevents immediate re-firing.
\end{enumerate}

\textbf{Immune system:} Layered defense.
\begin{itemize}
  \item \textbf{Innate}: Barriers, phagocytes (macrophages, neutrophils), and the \textbf{complement system} (protein cascade that lyses pathogens).
  \item \textbf{Adaptive}: \textbf{Humoral} (B cells producing antibodies) and \textbf{Cell-mediated} (T cells). \textbf{MHC class I} (on all nucleated cells) and \textbf{MHC class II} (on antigen-presenting cells) allow T cells to distinguish self from non-self.
  \item \textbf{Antibodies}: IgG (abundant), IgM (first response), IgA (mucosal). \textbf{Clonal selection} ensures only antigen-specific lymphocytes proliferate.
\end{itemize}

\textbf{Reproduction:} \textbf{Meiosis} reduces ploidy and generates variation via crossing over (Prophase I) and independent assortment. Human cycles are regulated by \textbf{FSH}, \textbf{LH}, estrogen, and progesterone.

For review, be able to: describe action potential phases; explain the sliding filament model; trace fluid through a nephron; explain the Bohr effect; distinguish MHC I and II.

\paragraph{Section summary}
Organisms maintain internal stability through complex physiological systems (nephrons, gas exchange, muscle sarcomeres). The nervous and immune systems provide rapid communication and targeted defense. Development and reproduction ensure the continuation of life via genetic regulation and meiosis.

\section{Ecology: Populations, Communities, Ecosystems, and Conservation}
\subsection{Core ideas}
\textbf{Population ecology} studies single-species dynamics. \textbf{Exponential growth} ($dN/dt = rN$) occurs under ideal conditions, while \textbf{logistic growth} ($dN/dt = rN(1 - N/K)$) incorporates the \textbf{carrying capacity} ($K$). Species are often classified as \textbf{r-selected} (unstable environments, high $r$) or \textbf{K-selected} (stable environments, near $K$).

\textbf{Community ecology} examines interspecific interactions:
\begin{itemize}
  \item \textbf{Competition} ($-$/$-$): \textbf{Gause's Law} (Competitive Exclusion Principle) states that two species competing for the exact same limiting resource cannot coexist; one will be more efficient and outcompete the other. This drives \textbf{niche partitioning}.
  \item \textbf{Exploitation} ($+$/$-$): Includes \textbf{predation}, \textbf{herbivory}, and \textbf{parasitism}. \textbf{Trophic cascades} occur when predators limit the density or behavior of their prey, thereby enhancing the survival of the next lower trophic level (e.g., wolves in Yellowstone).
  \item \textbf{Control Mechanisms}: \textbf{Bottom-up} control (resource availability limits higher levels) vs. \textbf{Top-down} control (predation limits lower levels).
  \item \textbf{Symbiosis}: \textbf{Mutualism} ($+$/$+$, e.g., coral and zooxanthellae) and \textbf{Commensalism} ($+$/0).
  \item \textbf{Keystone species}: Organisms that have an outsized impact on community structure relative to their abundance (e.g., Pisaster starfish).
\end{itemize}

\textbf{Ecosystem ecology} tracks energy flow and chemical cycling. Energy flows one-way, with $\sim 10\%$ efficiency between trophic levels (\textbf{Lindeman's Rule}). Key cycles: \textbf{Carbon} (driven by photosynthesis and respiration), \textbf{Nitrogen} (requiring bacterial fixation, nitrification, and denitrification), and \textbf{Phosphorus}.

\textbf{Conservation biology} addresses the biodiversity crisis. \textbf{Island Biogeography} (MacArthur and Wilson) predicts that species richness on an island is determined by a balance between immigration and extinction, which are functions of the island's \textbf{size} (affecting extinction) and \textbf{distance} from the mainland (affecting immigration). This theory informs the design of \textbf{protected areas} and \textbf{habitat corridors}.

For review, be able to: solve growth equations; apply Gause's Law; explain trophic cascades (top-down control); diagram the nitrogen cycle; use island biogeography to predict species richness.

\paragraph{Section summary}
Ecology scales from populations (growth and r/K strategies) to communities (competition and trophic cascades) and ecosystems (energy flow and nutrient cycling). Conservation biology applies these models, such as island biogeography, to mitigate habitat loss and protect global biodiversity.

\section{Experiments and Data: Analytical Methods, Statistics, and Ethics}
\subsection{Core ideas}
\textbf{The scientific method} relies on \textbf{falsifiability} (Karl Popper). A hypothesis is a testable explanation; the \textbf{null hypothesis} ($H_0$) posits no effect. Experiments must include \textbf{controls} (positive/negative), \textbf{randomization}, and \textbf{replication} to ensure results are not due to chance or bias.

\textbf{Statistics} allow for \textbf{hypothesis testing}.
\begin{itemize}
  \item \textbf{Significance}: The \textbf{p-value} is the probability of obtaining results at least as extreme as the ones observed, assuming $H_0$ is true. If $p < \alpha$ (usually $0.05$), we reject $H_0$.
  \item \textbf{Errors}: \textbf{Type I error} ($\alpha$) is a false positive (rejecting $H_0$ when it is true). \textbf{Type II error} ($\beta$) is a false negative (failing to reject $H_0$ when it is false). \textbf{Power} ($1-\beta$) is the probability of correctly rejecting a false $H_0$.
  \item \textbf{Tests}: \textbf{t-test} (compares 2 means), \textbf{ANOVA} (compares $>2$ means), \textbf{Chi-square} (tests categorical associations), and \textbf{Regression} (models variable relationships, $R^2$ measures fit).
\end{itemize}

\textbf{Molecular Techniques} are the engine of modern biology.
\begin{itemize}
  \item \textbf{PCR} (Polymerase Chain Reaction): A technique to amplify specific DNA sequences. Three steps: 1) \textbf{Denaturation} (heat to separate strands), 2) \textbf{Annealing} (cool to allow primers to bind), and 3) \textbf{Extension} (DNA polymerase adds nucleotides).
  \item \textbf{Sequencing}: \textbf{Sanger sequencing} (chain termination method using ddNTPs) is the gold standard for small-scale sequencing. \textbf{Next-Generation Sequencing} (NGS) allows for massive parallel sequencing of entire genomes.
  \item \textbf{Electrophoresis}: Separates DNA/RNA/proteins by size using an electric field; smaller fragments travel faster through a gel matrix.
\end{itemize}

\textbf{Research Ethics} involves protecting participants and ensuring integrity. The \textbf{3Rs} (Replacement, Reduction, Refinement) guide animal research. \textbf{Bioethics} explores the implications of technologies like CRISPR, cloning, and stem cell therapy.

For review, be able to: design a controlled experiment; interpret p-values and error types; list PCR steps; explain Sanger sequencing; discuss the 3Rs in ethics.

\paragraph{Section summary}
Biological progress depends on the scientific method, rigorous statistical validation (p-values, Type I/II errors), and advanced molecular tools like PCR and NGS. Ethical frameworks, such as the 3Rs, ensure that this progress is achieved responsibly.

\end{document}
