Bio pt2

Anaerobic Fermentation and Cellular Metabolism

• Fermentation is a process by which energy is harvested from sugar without the use of oxygen ($O_2$). It is a form of anaerobic metabolism.

• While aerobic cellular respiration utilizes oxygen to break down glucose ($C_6H_{12}O_6$) into carbon dioxide ($CO_2$), water ($H_2O$), and a significant amount of ATP, fermentation produces far less ATP per molecule of glucose.

• The breakdown of glucose always begins with glycolysis, which splits one glucose molecule into two molecules of pyruvic acid. This process requires $NAD^+$ to pick up electrons, becoming $NADH$.

• Fermentation allows for the recycling of $NAD^+$ so that glycolysis can continue in the absence of oxygen.

• Lactic Acid Fermentation in Human Muscles:

  • When muscles are overexerted and oxygen supply cannot keep up with demand, they switch to an "emergency mode."

  • Glucose is fermented to produce lactic acid and a small amount of ATP.

  • This mode is not sustainable; after a few minutes, muscles stop functioning and the individual may collapse.

• Lactic Acid Fermentation by Bacteria:

  • Many microorganisms use fermentation for all their energy needs.

  • Some bacteria produce lactic acid, which humans use to produce foods with "sharp" tastes like olives, yogurt, pepperoni, and pickles.

• Alcohol Fermentation by Yeast:

  • In an anaerobic environment, yeast ferments sugars to produce $CO_2$ and ethyl alcohol (ethanol).

  • This is used in the production of beer and sparkling wines.

  • In baking, the $CO_2$ causes bread to rise, while the alcohol is baked off. Grain has been fermented to produce beer for at least $5,500$ years.

• Metabolism and Energy Sources:

  • Metabolism is the sum total of all chemical reactions occurring in the body. ATP is the central currency of metabolism: all food energy leads to it, and all bodily work is powered by it.

  • While glucose is the primary fuel, the body can obtain energy from other carbohydrates, fats, and proteins.

  • Fats provide twice as much ATP per ounce compared to carbohydrates or proteins.

Cell Division and Chromosome Structure

• Cell Theory states that all life is cellular and all cells arise from preexisting cells. Cell division underlies growth, repair, development, and reproduction.

• Sexual Reproduction:

  • Formation of genetically unique offspring via the fusion of gametes (sperm and egg).

  • Fertilization produces a single-celled zygote, which then develops into an embryo, fetus, baby, and adult through repeated cell division.

• Asexual Reproduction:

  • Creation of a new individual by a lone parent, resulting in genetically identical offspring.

  • Binary Fission: Single-celled organisms like the protist Amoeba proteus or the algae Micrasterias split into two.

  • Plant Reproduction: Many plants use sprouts (like potato "eyes") or runners (like strawberries) to reproduce asexually.

  • Regeneration: Some animals, like sea stars, can grow back limbs or even an entire body from a fragment.

• Chromosome Composition:

  • In eukaryotes, almost all genes are located on chromosomes in the nucleus.

  • Chromatin: An association of one very long DNA molecule and proteins that help compact and organize it.

  • Human body cells contain $46$ chromosomes. The DNA from two humans of the same sex is approximately $99.5\%$ identical, meaning only $0.5\%$ accounts for unique traits.

  • Sister Chromatids: Before a cell divides, it duplicates its chromosomes. The two identical copies are called sister chromatids and are joined at the centromere.

The Cell Cycle and Mitosis

• The cell cycle is an ordered sequence of events from a cell's creation to its own division. It consists of two broad stages:

• Interphase:

  • Accounts for roughly $90\%$ of the cell cycle.

  • The cell performs normal functions, doubles in size, builds cytoplasm and organelles, and duplicates chromosomes within the nucleus.

  • Chromosomes remain in an uncondensed state.

• Mitotic Phase:

  • The cell actually divides. It is comprised of two overlapping stages: Mitosis (division of the nucleus) and Cytokinesis (division of the cytoplasm).

  • Result: Two genetically identical offspring cells.

• Stages of Mitosis:

  • Prophase: Nuclear membrane dissolves; chromosomes condense and become visible; the mitotic spindle forms.

  • Metaphase: Duplicated chromosomes align at the center of the cell, attached to the mitotic spindle.

  • Anaphase: Sister chromatids split apart and are dragged by the spindle to opposite ends of the cell.

  • Telophase: Nuclear membrane reforms; chromosomes uncondense; the nucleus is now duplicated.

• Cytokinesis Differences:

  • Animal Cells: Proceed via cleavage. A cleavage furrow, made of a ring of protein filaments (actin and myosin), pinches the cell in two.

  • Plant Cells: Because of the stiff cell wall, they form a cell plate. A strip of membrane and cell wall material forms at the center and fuses with the plasma membrane.

Cloning and Stem Cells

• Clones are genetically identical individuals born of a single parent.

• Nuclear Transplantation:

  • A nucleus is removed from an adult donor cell and injected into a nucleus-free egg cell.

  • This produces an embryo that is a clone of the individual that provided the adult nucleus.

• Plant Cloning:

  • Widely used in agriculture (e.g., orchids, navel oranges, wine grapes). All seedless navel oranges are clones from a single tree discovered in Brazil in $1869$.

• Reproductive vs. Therapeutic Cloning:

  • Reproductive Cloning: The embryo is implanted into a surrogate mother to develop into a new living individual (e.g., Dolly the sheep in $1997$, horses, dogs, cats).

  • Therapeutic Cloning: Stem cells are harvested from the cloned embryo. Embryonic stem cells have the potential to develop into every cell type in the body. Other sources include adult bone marrow and umbilical cord blood.

Meiosis and the Human Life Cycle

• Somatic cells are diploid ($2n$), meaning they contain two sets of chromosomes. In humans, $2n = 46$.

• Gametes (sperm and egg) are haploid ($n$), containing one set of chromosomes ($n = 23$). These are produced via meiosis in the gonads (testes and ovaries).

• The Life Cycle Timeline:

  • Fertilization: Two haploid gametes fuse to form a diploid zygote ($23 + 23 = 46$).

  • Development: The zygote undergoes cell division to become an adult.

  • Gamete Formation: The adult produces new haploid gametes via meiosis.

• Karyotypes and Homologous Chromosomes:

  • A karyotype is a photographic inventory of chromosomes.

  • Homologous pairs are matching pairs of chromosomes that carry genes for the same characteristics in the same order.

  • Humans have $23$ pairs. $22$ pairs are autosomes. The $23^{rd}$ pair is the sex chromosomes: $XX$ for females and $XY$ for males.

• Stages of Meiosis:

  • Meiosis I: Homologous pairs line up and then separate. Each chromosome still consists of two sister chromatids. This results in two haploid cells.

  • Meiosis II: Sister chromatids separate (similar to mitosis). This results in four haploid offspring cells.

Sources of Genetic Variation

• Sexual reproduction generates variety through three main processes:

• Independent Assortment:

  • Homologous pairs line up randomly in Meiosis I. There are $2^{23}$ (over $8$ million) possible combinations of maternal and paternal chromosomes.

• Random Fertilization:

  • One random sperm ($8$ million possibilities) fertilizes one random egg ($8$ million possibilities), resulting in $64$ trillion possible combinations in the zygote.

• Crossing Over:

  • During Meiosis I, homologous chromosomes swap pieces. This produces hybrid recombinant chromosomes with new combinations of genes.

Chromosomal Abnormalities

• Nondisjunction is a mishap where chromosomes fail to separate properly during meiosis. This results in gametes with $n + 1$ or $n - 1$ chromosomes.

• Autosomal Abnormalities:

  • Trisomy 21: Three copies of chromosome $21$. Results in Down syndrome, characterized by short stature, heart defects, developmental delays, and distinct facial features.

• Sex Chromosome Abnormalities:

  • Klinefelter Syndrome ($XXY$): Male; sterile; underdeveloped testes; some feminine features.

  • Jacob’s Syndrome ($XYY$): Male; often taller than average.

  • Triple-X Syndrome ($XXX$): Female; slightly taller; risk of learning delays.

  • Turner Syndrome ($XO$): Female; sterile; immature sex organs. This is the only known case where having only $45$ chromosomes is not fatal.

Principles of Mendelian Genetics

• Gregor Mendel (1822–1884) studied pea plants to deduce the principles of inheritance.

• Basic Terminology:

  • Character: An inherited feature that varies (e.g., flower color).

  • Trait: Each variation of a character (e.g., purple or white).

  • Alleles: Alternate forms of a gene. Homozygous implies two identical alleles; heterozygous implies two different alleles.

  • Genotype: The underlying genetic makeup.

  • Phenotype: The observable traits.

• Dominance:

  • A dominant allele (uppercase) determines the appearance in a heterozygote.

  • A recessive allele (lowercase) has no effect unless the organism is homozygous recessive.

• Law of Segregation:

  • Pairs of alleles separate during gamete formation so that each gamete carries only one allele for each gene.

• Monohybrid and Dihybrid Crosses:

  • Monohybrid Cross: Follows one character. A cross between two heterozygotes results in a $3:1$ phenotype ratio.

  • Dihybrid Cross: Follows two characters. Mendel's Law of Independent Assortment states that the inheritance of one character does not affect another. A dihybrid cross between heterozygotes typically results in a $9:3:3:1$ phenotype ratio.

• Testcross:

  • Mating an individual of unknown genotype (dominant phenotype) with a homozygous recessive individual to determine the unknown's makeup.

Complex Inheritance Patterns

• Incomplete Dominance: Heterozygotes have an intermediate appearance (e.g., pink snapdragons from red and white parents).

• Multiple Alleles and Codominance:

  • Human Blood Types: Three alleles ($i$, $I^A$, $I^B$). $I^A$ and $I^B$ are codominant, meaning both are expressed (e.g., Type AB).

• Pleiotropy: One gene influences many characters (e.g., the mutation causing sickle-cell disease affects blood shape, pain, and organ health).

• Polygenic Inheritance: Many genes affect a single character, creating a continuum of traits (e.g., human height and skin color).

• Linked Genes: Genes located near each other on the same chromosome tend to be inherited together. They can only be separated by crossing over. Recombination frequency increases with the distance between genes.

• Sex-Linked Genes:

  • Genes located on the X chromosome display unique patterns because males have only one X. Recessive disorders like hemophilia and color blindness are more common in men ($17:1$ ratio for color blindness).

DNA Structure and Replication

• DNA (Deoxyribonucleic Acid) is a polymer of nucleotides. Each nucleotide consists of:

  • A five-carbon sugar (deoxyribose).

  • A negatively charged phosphate.

  • A nitrogenous base (Adenine, Guanine, Thymine, or Cytosine).

• Double Helix Structure:

  • Two polynucleotide strands wrap around each other.

  • The sugar-phosphate backbone is on the outside.

  • Hydrogen bonds connect base pairs in the center: $A$ with $T$ ($2$ bonds), $C$ with $G$ ($3$ bonds).

• DNA Replication:

  • Occurs via a semi-conservative model: each new molecule has one original strand and one new strand.

  • Helicase: Enzyme that peels apart the double helix at origins of replication.

  • DNA Polymerase: Builds new complementary strands.

  • DNA Ligase: Fuses fragments together.

The Flow of Genetic Information

• Information flow: DNA $\rightarrow$ RNA $\rightarrow$ Protein.

• DNA vs. RNA:

  • DNA: Double-stranded, deoxyribose sugar, Thymine ($T$).

  • RNA: Single-stranded, ribose sugar, Uracil ($U$) instead of $T$.

• Transcription (In the Nucleus):

  • RNA Polymerase binds to a promoter sequence and creates mRNA from a DNA template.

  • Ends at a terminator sequence.

  • Splicing: Introns (noncoding) are removed; exons (coding) are joined. A cap and tail are added.

• Translation (In the Cytoplasm):

  • Ribosomes coordinate mRNA, tRNA, and rRNA.

  • mRNA carries codons (triplets of nucleotides). There are $64$ possible codons but only $20$ amino acids.

  • tRNA has an anticodon on one end and a specific amino acid on the other.

  • Process: Initiation (ribosome assembles at start codon $AUG$), Elongation (amino acids added to polypeptide), Termination (ribosome reaches stop codon $UAA, UAG, \text{ or } UGA$).

Gene Regulation and Signaling

• Gene Regulation: Mechanisms that turn genes on or off.

• Methods of Regulation:

  • Transcription Factors: Proteins that must bind to DNA to initiate transcription.

  • X Chromosome Inactivation: In female mammals, one X chromosome is compacted into a Barr body.

  • Alternate Splicing: Joining exons in different ways to produce different proteins from one gene.

  • microRNAs: Small RNA molecules that bind to and prevent mRNA from being translated.

• Cell-to-Cell Signaling:

  • Signal Transduction Pathway: A series of relay molecules that convey a message from outside the cell to the nucleus, usually resulting in gene regulation.

  • Induction: One group of cells influences the development of neighbors (e.g., removing webbing between fingers).

  • Homeotic Genes: Master control genes that establish body structures (e.g., head vs. tail location).

Mutations and Cancer

• Mutation: Any change to genetic information.

• Mutagens: Physical or chemical agents that cause mutations (e.g., UV radiation, X-rays, tobacco).

• Point Mutations (Single Nucleotide Substitution):

  • Silent: No change in amino acid.

  • Missense: Substitutes one amino acid for another.

  • Nonsense: Changes a codon to a stop codon, shortening the protein.

• Frameshift Mutations (Insertions or Deletions):

  • Shift the reading frame, often producing a completely defective protein.

• Cancer and the Cell Cycle:

  • Proto-oncogene: Normal gene that regulates the cell cycle.

  • Oncogene: Mutated proto-oncogene that causes out-of-control growth.

  • Growth Factors: Proteins that promote cell division. Mutations can make them hyperactive.

  • Tumor-Suppressor Genes: Proteins that inhibit division. Mutations can deactivate them (e.g., $p53$ is mutated in $50\%$ of human tumors).

• Cancer Progression and Treatment:

  • Benign Tumor: Mass of cells that cannot spread.

  • Malignant Tumor: Capable of spreading (Cancer).

  • Metastasis: The spread of cancer cells beyond their site of origin.

  • Treatments: Surgery, Radiation Therapy (local), and Chemotherapy (systemic).

DNA Technology and Biotechnology

• Genetic Engineering: Direct manipulation of genes for practical purposes.

• Restriction Enzymes: Proteins that cut DNA at specific restriction sites. Often produce "sticky ends."

• DNA Cloning: Using bacterial plasmids (small circular DNA) to produce large quantities of a protein (e.g., human insulin approved in $1982$).

• Genomic Library: A collection of DNA fragments representing an entire genome.

• CRISPR-Cas9: A system using a Cas9 protein and guide RNA to cut and edit specific DNA sequences in living cells.

• PCR (Polymerase Chain Reaction):

  • Uses a heat-stable DNA polymerase to double a target DNA segment through cycles of heating and cooling.

  • Requires primers to flank the target sequence.

• DNA Profiling:

  • STR Analysis: Compares the lengths of short tandem repeats at $13$ predefined sites.

  • Gel Electrophoresis: Separates DNA fragments by size using electrical current. DNA is negatively charged and migrates toward the positive pole.

• Genomics and Gene Therapy:

  • Human Genome Project (completed $2003$): Found $21,000$ genes in $3$ billion nucleotides. Only $1.5\%$ codes for proteins.

  • Proteomics: The study of the full set of proteins ($100,000$ in humans).

  • Gene Therapy: Using viruses (like retroviruses) to insert healthy genes into patients with genetic diseases like SCID.

Evolutionary Theory and Evidence

• Charles Darwin published On the Origin of Species in $1859$, proposing evolution by natural selection ("descent with modification").

• Influence and Context:

  • Ancient Greeks (Aristotle): Species are permanent.

  • Middle Ages: Literal biblical interpretation (Earth $5,000$ years old).

  • Lyell: Gradual geologic change.

  • Lamarck: Suggested life evolves through physical changes.

• The Argument for Natural Selection:

  • Overproduction + Limited Resources $\rightarrow$ Competition.

  • Variability + Heritability $\rightarrow$ Natural Selection (Unequal reproductive success).

  • Evolution is a generation-to-generation change in populations, not individuals.

• Artificial Selection: Human-enforced selective breeding (e.g., dog breeds from wolves, modern strawberries).

• Evidence for Evolution:

  • Fossil Record: Ordered sequence of fossils in rock layers. Older fossils are deeper.

  • Radiometric Dating: Measuring isotopes like $C-14$ (half-life of $5,700$ years).

  • Biogeography: Geographic distribution of species (e.g., marsupials in Australia).

  • Comparative Anatomy: Similarities in structures (homologies like mammal forelimbs) suggest common ancestry.

  • Bioinformatics: Comparison of DNA and protein sequences. Humans/Chimpanzees are $96\%-100\%$ identical in selected sequences.

Populations and Macroevolution

• Microevolution: Change in a population's gene pool over time. Driven by mutations and sexual recombination.

• Darwinian Fitness: Measured only by the number of healthy offspring produced.

• Mechanisms of Evolution:

  • Genetic Drift: Chance changes in a small population. Bottleneck Effect (drastic reduction) and Founder Effect (small new colony).

  • Gene Flow: Exchange of genes via migration.

  • Sexual Selection: Certain traits increase mating chances.

• Macroevolution:

  • Speciation: Formation of new species. Branching evolution increases diversity.

  • Geologic Record: Earth's history ($4.6$ billion years) divided into eras (Precambrian, Paleozoic, Mesozoic, Cenozoic).

  • Plate Tectonics: Movement of the Earth's crust (Pangea split $200$ million years ago).

  • Mass Extinctions: Five major events (e.g., KT extinction $65$ million years ago wiped out dinosaurs and allowed mammal diversification).

• Species Recognition:

  • Biological Species Concept: Group capable of interbreeding to produce fertile offspring.

  • Reproductive Barriers: Behavioral isolation, mating time differences, habitat isolation, mechanical incompatibility, gametic incompatibility, and hybrid weakness.

• Speciation Models:

  • Graduated Model: Slow, gradual change over millions of years.

  • Punctuated Equilibrium: Long periods of stasis interrupted by bursts of rapid change (e.g., Cambrian explosion $530$ million years ago).

Questions & Discussion

• Q: What gas is contained within champagne bubbles? Where does it come from?

• A: Champagne bubbles contain $CO_2$, produced through fermentation by yeast.

• Q: What molecule serves as the central currency of energy in all your cells? From what molecule is it made?

• A: ATP; it is made from ADP.

• Q: From a cell division perspective, why are all of the trillions of cells in your body genetically identical?

• A: Because they all descended via cell division from a single original cell (the zygote).

• Q: How many individual pieces of DNA are in the nucleus of each of your body cells?

• A: $46$, one long piece of DNA for each chromosome.

• Q: Explain why the following statement is incorrect: "During mitosis, chromosomes are duplicated and distributed."

• A: Because the chromosomes are already duplicated (during interphase) by the time the mitotic phase starts.

• Q: What would happen if one pair of sister chromatids failed to split during mitosis?

• A: One offspring cell would have one chromosome too many, and the other offspring cell would have one chromosome too few.

• Q: Why can’t a plant cell pinch inward and form a cleavage furrow?

• A: All plant cells are surrounded by a stiff cell wall that prevents pinching inward.

• Q: If a nucleus is removed from a brown mouse, injected into a nucleus-free egg from a white mouse, and the resulting embryo is implanted in a black mouse, what color will the babies be?

• A: Brown (since that is the source of the nucleus).

• Q: If you examine a human cell and observe that it has $23$ chromosomes including one Y chromosome, where must it be from?

• A: It must be from a sperm cell (since it is haploid and has a Y chromosome).

• Q: What is the key feature of meiosis I with respect to the arrangement of chromosomes?

• A: The chromosomes line up by homologous pairs (rather than singly).

• Q: Is a chromosome in one of your gametes likely to be just like one that you received from your parents?

• A: No. Due to crossing over, most chromosomes in your gametes are hybrids.

• Q: Which two extensions of Mendelian genetics discussed here are essentially the opposite of each other?

• A: Pleiotropy (one gene affects many characters) and polygenic inheritance (many genes affect one character).