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Genes and Cellular Function - Vocabulary

DNA Structure and Function

  • DNA stands for deoxyribonucleic acid; a long, thread-like molecule with uniform diameter but varied length

  • In most human cells, there are 46 DNA molecules (chromosomes) in the nucleus

  • Average length of a human DNA molecule is about 2\text{ inches}, leading to the concept that the genome is extremely compacted within the nucleus

  • DNA and other nucleic acids are polymers of nucleotides

  • Each nucleotide consists of three components:

    • A sugar: deoxyribose

    • A phosphate group

    • A nitrogenous base

  • DNA bases: A, T, C, G

  • Purines: adenine (A) and guanine (G); double-ringed structures

  • Pyrimidines: cytosine (C), thymine (T), and in RNA uracil (U); single-ringed structures

  • The five nitrogenous bases found in DNA and RNA are depicted in the figures

  • The double helix structure is formed by two long strands with a sugar-phosphate backbone; base pairs form the steps of the ladder

  • Base pairing rules (law of complementary base pairing):

    • A with T via 2 hydrogen bonds

    • G with C via 3 hydrogen bonds

  • The essential function of DNA is to carry instructions (genes) for the synthesis of proteins

  • Gene: a segment of DNA that codes for the synthesis of a specific protein

  • Humans have about 20{,}000 genes; only about 2\% of total DNA codes for genes; the remaining 98\% is noncoding DNA

  • Noncoding DNA contributes to chromosome structure and regulates gene activity

  • DNA carries the genetic information that directs protein synthesis through transcription and translation

Organization of Chromatin

  • Chromatin is threadlike DNA associated with histone proteins; the basic unit is the nucleosome

  • In nondividing (interphase) cells, DNA is compacted but not uniformly folded; it can change conformation in response to genetic activity

  • DNA length in nucleus is about 2\text{ m} when fully extended, but it is compacted to fit a nucleus

  • Core particle (histone complex) is ~11\text{ nm} in diameter; linker DNA connects nucleosomes

  • Nucleosome refers to DNA wound around a histone core; ~11\text{ nm} diameter

  • The DNA-histone complex further folds into higher-order structures:

    • 30 nm fiber formed by folded nucleosomes (accordion-like compaction)

    • Further looping forms a thicker fiber (~300 nm)

    • In dividing cells, chromatin fibers coil into ~700\text{ nm} fibers to form chromatids

  • Prior to cell division, DNA is copied to form two parallel sister chromatids; chromatids are held at the centromere; kinetochores assist in chromosome movement during cell division

  • Chromosome territories: in the nucleus, each chromosome occupies its own distinct region

  • The chromatin architecture is dynamic: gene activation or silencing changes spatial organization

DNA Structure

  • DNA is a double helix; each strand has a sugar-phosphate backbone with nitrogenous bases facing inward

  • Bases pair specifically: A with T (two hydrogen bonds), G with C (three hydrogen bonds)

  • The two strands run in opposite directions (antiparallel)

  • Figure 4.2 illustrates the backbone (sugar-phosphate) and the base-pairing interactions

  • Sugar-phosphate backbone is continuous on each strand; hydrogen bonds connect the complementary bases across the two strands

RNA Structure and Function

  • RNA (ribonucleic acid) is structurally distinct from DNA

  • RNA contains the sugar ribose; bases A, U, G, C (uracil replaces thymine in RNA)

  • RNA usually exists as a single strand (not a double helix) but can have short regions of double-strandedness

  • RNA molecules are smaller than DNA; typical lengths range from fewer than 100 bases to around 10,000 bases

  • RNA functions mainly in the cytoplasm

  • Three major RNAs necessary for protein synthesis:

    • Messenger RNA (mRNA): carries genetic information from DNA to the ribosome

    • Ribosomal RNA (rRNA): structural and functional component of ribosomes

    • Transfer RNA (tRNA): delivers amino acids to the ribosome during protein synthesis

  • Sugar: ribose in RNA vs deoxyribose in DNA

  • Bases: A, U, G, C in RNA vs A, T, G, C in DNA

  • RNA is usually single-stranded; DNA is usually double-stranded

  • Comparison of DNA and RNA (highlights):

    • DNA: sugar = deoxyribose; bases A, T, C, G; typically two strands; nucleus; codes for RNA and protein; very stable

    • RNA: sugar = ribose; bases A, U, G, C; single strand (primarily); functions in cytoplasm; translates DNA code into protein; more transient

Genetic Control of Cell Action Through Protein Synthesis

  • DNA directs the synthesis of all cellular proteins; genes are recipes for proteins

  • Different cells synthesize different proteins, giving each cell its specialized function

    • Example: ovary cells produce estrogens and progesterone; pancreas cells produce insulin

Stages of Protein Synthesis

  • Two main steps: Transcription and Translation

  • Step 1: Transcription (nucleus)

    • DNA serves as the template for RNA synthesis

    • RNA polymerase binds to start sequences in DNA, opens the helix, and reads bases on one DNA strand to build a complementary mRNA strand

    • Rule of base pairing during transcription:

    • When the DNA template has C, the mRNA has G

    • When the DNA template has G, the mRNA has C

    • When the DNA template has T, the mRNA has A

    • When the DNA template has A, the mRNA has U

  • Step 2: Translation (cytoplasm, ribosome)

    • mRNA codes are read by the ribosome to assemble amino acids into a protein

    • tRNA delivers amino acids to the ribosome and contains an anticodon that pairs with the mRNA codon

    • The ribosome has a small and a large subunit; it binds mRNA and tRNA; translation occurs at A, P, and E sites

Protein Synthesis: Details and Visuals

  • Start of translation: the mRNA strand binds to the small ribosomal subunit; the first tRNA carries the amino acid methionine and binds at the start codon

  • Start codon is typically AUG

  • Codon-anticodon pairing occurs via complementary base pairing between mRNA codons and tRNA anticodons

  • The amino acid chain grows as successive tRNAs deliver amino acids

  • Stop codons indicate termination: UAG, UGA, UAA

  • The process continues until a stop codon is reached, releasing the polypeptide and dissociating the ribosome

  • During translation, energy is consumed (ATP and GTP usage) for tRNA charging and ribosome movement; subsequent steps utilize resources like amino acids and ATP

  • The assembling polypeptide chain is the growing protein; after synthesis, the protein may undergo post-translational modifications

Posttranslational Modification

  • Proteins synthesized on the Rough Endoplasmic Reticulum (RER) are directed into the ER by signal peptides

  • Modifications in the rough ER include:

    • Removal of amino acids, proper folding, formation of disulfide bridges (S-S bonds), and addition of carbohydrate groups

    • Vesicles bud from the ER and transport proteins to the Golgi complex

  • In the Golgi complex, proteins are further modified as they move through cisternae; the final product is released in secretory vesicles or directed to lysosomes

  • Secretory vesicles migrate to the cell membrane and release products via exocytosis

  • Some proteins remain in the cell within lysosomes

  • Membrane proteins are processed and delivered to membranes

DNA Replication and the Cell Cycle

  • Before cell division, the cell must duplicate its DNA to give a complete copy to each daughter cell; accuracy is critical since DNA controls cellular function

  • Four steps of DNA replication: 1) Unwinding the helix from histones 2) Unzipping a portion of the helix by DNA helicase to form a replication fork 3) DNA polymerase moves along each strand, reads exposed bases, and synthesizes complementary new strands; on the discontinuous strand, short segments are connected by DNA ligase

    • Replication is semiconservative: each new DNA molecule contains old parental DNA and newly synthesized DNA
      4) New histones are synthesized to organize the new DNA strands into nucleosomes

  • Replication is highly accurate due to proofreading by DNA polymerase and repair systems; error rates drop from roughly 3\times 10^{-5} to about 1\times 10^{-9} errors per base copied

  • Mutations: changes in DNA structure due to replication errors or environmental factors; consequences range from no effect to cell death or cancer or inherited defects

The Cell Cycle and Interphase/Mitosis

  • The cell cycle spans from cell formation to division

  • Cells divide for growth, repair, development, and replacement of dead cells; not all cells divide continuously (e.g., some neurons and muscle cells stay in G0)

  • Phases:

    • Interphase: growth and DNA synthesis (G1, S, G2)

    • Mitotic phase (M): cell division (mitosis) and cytokinesis

  • Interphase details:

    • G1: growth and normal metabolic roles; varies from hours to days to years; centrosomes/centrioles duplicated; accumulates materials needed to replicate DNA

    • S: synthesis; DNA replication occurs (about 6-8\text{ hours})

    • G2: growth and final preparation for division; enzymes for division synthesized (about 4-6\text{ hours})

  • Mitosis stages (mitotic phase): Prophase, Metaphase, Anaphase, Telophase; followed by Cytokinesis

  • Prophase: chromatin condenses into chromosomes (46 chromosomes; 2 chromatids per chromosome); nuclear envelope breaks down; spindle apparatus forms; centrioles move to poles; kinetochores form at centromeres

  • Metaphase: chromosomes align at the cell equator; spindle apparatus forms an aster; spindle fibers attach to kinetochores

  • Anaphase: sister chromatids separated at the centromere and pulled to opposite poles by shortening microtubules

  • Telophase: chromosomes cluster at poles; nuclear envelope re-forms; chromosomes de-condense into chromatin; mitotic spindle disassembles; nucleoli reappear

  • Cytokinesis: division of cytoplasm; in animal cells, a contractile ring forms a cleavage furrow that pinches the cell membrane inward to split the cell; in plant cells, vesicles coalesce to form a cell plate that becomes a separating cell wall

Chromosomes and Heredity

  • Heredity: transmission of genetic characteristics from parent to offspring

  • Karyotype: chart of all 46 chromosomes laid out in order by size

  • 23 pairs of homologous chromosomes

  • Homologous chromosomes: one chromosome from each parent per pair

  • Autosomes: 22 pairs that look alike and carry the same genes

  • Sex chromosomes: 1 pair; females have two X chromosomes (XX); males have one X and one Y chromosome (XY)

  • Diploid (2n): describes cells with 23 pairs of chromosomes; Somatic cells are diploid

  • Haploid (n): cells with half as many chromosomes as somatic cells; human haploid number is 23; germ cells (sperm and eggs) are haploid; fertilization restores diploid number in the zygote

Genes, Alleles, and Inheritance

  • Locus: a gene’s position on a chromosome

  • Alleles: different forms of a gene; located at the same locus on homologous chromosomes

  • Dominant allele (capital letter): when present, the trait is usually seen; masks the recessive allele; often produces functional protein

  • Recessive allele (lowercase letter): trait seen only when present on both homologous chromosomes; often codes for a nonfunctional protein

  • Genotype: the alleles an individual possesses for a gene

    • Homozygous: two identical alleles for the gene

    • Heterozygous: two different alleles for the gene

  • Phenotype: observable trait; often determined by multiple genes, but some traits arise from a single gene

  • Example: Sickle-cell disease is caused by homozygous recessive alleles (HbS) in the beta-globin gene

Sickle-Cell Disease (Genetics Example)

  • Visual depiction shows different red blood cell (RBC) shapes:

    • Homozygous dominant (HH): Normal RBCs

    • Heterozygous (Hh): Normal RBCs (carrier with sickle-cell trait)

    • Homozygous recessive (hh): Sickled RBCs

  • Inheritance pattern: autosomal recessive; individuals with two HbS alleles (hh) exhibit disease; carriers (Hh) are typically asymptomatic or have mild symptoms

  • Significance: demonstrates how a single gene can influence cell shape and oxygen transport; carrier state can convey some protection against malaria in heterozygotes in some populations

Cancer: Genetics, Oncogenes, and Tumor Suppressor Genes

  • Cancer: tumors (neoplasms) are abnormal growths where cells multiply faster than they die

  • Benign tumors: encapsulated, slow growth, local effects; generally less dangerous unless they compress vital tissues

  • Malignant tumors (cancer): not encapsulated, grow rapidly, invasive, capable of metastasis; can stimulate angiogenesis

  • Classification by tissue origin: carcinoma (epithelial), melanoma (melanocytes), sarcoma (bone, muscle, or other connective tissue), leukemia (blood), lymphoma (lymph nodes)

  • Causes: 60–70% from environmental agents (carcinogens), including chemicals (cigarette smoke, food preservatives, industrial chemicals), radiation, and viruses that damage DNA; mutagens can initiate cancer

  • Malignant tumor genes and pathways:

    • Proto-oncogenes: normal genes that promote cell growth; when mutated, become oncogenes leading to excessive growth factor production or receptors (e.g., sis, ras)

    • Tumor suppressor genes (TS genes): normally inhibit cancer development; mutations or silencing remove cell cycle control, promoting uncontrolled growth

  • Consequences: displacing normal tissue, impairing organ function, blocking vital paths, diverting nutrients, high metabolic rate in tumors causing weakness and fatigue (cachexia)

  • Defenses include scavenger cells, peroxisomes, DNA repair enzymes, macrophages/monocytes releasing tumor necrosis factor (TNF), natural killer cells

Metastasis and Cancer Progression

  • Metastasis: spread of cancer cells from a primary tumor to distant sites
    1) Malignant cells invade blood or lymphatic vessels
    2) Cells travel to new sites
    3) Cells exit vessels and establish metastatic tumors at new sites

  • Secondary tumors reflect the spread of cancerous cells; metastatic tumors are clinically significant for prognosis and treatment

Genetic Information and Codon-to-Amino-Acid Translation (Illustrative Example)

  • DNA base triplets (codons) in the template strand are transcribed to mRNA codons; the mRNA sequence is translated into amino acids by tRNA anticodons

  • Example from the notes:

    • DNA template strand: TAC CGC CCT TGC GTA CTC ACT

    • mRNA codons transcribed: AUG GCG GGA ACG CAU GAG UGA

    • Start codon: AUG; Stop codon: UGA

    • The corresponding amino acids carried by tRNA anticodons yield a sequence: Met - Ala - Gly - Thr - His - Glu - (Stop)

  • The mRNA codons and tRNA anticodons pair by complementary base pairing during translation

  • Final protein sequence and its folding determine function; posttranslational modifications can further alter activity and localization

Important Codon and Anticodon Concepts

  • Start codon: AUG (codes for Methionine, MET)

  • Stop codons: UAG, UGA, UAA (signal termination of translation)

  • Anticodon: a set of three nucleotides on tRNA complementary to the mRNA codon

  • Ribosome structure and function:

    • Small ribosomal subunit binds mRNA leader sequence and coordinates tRNA binding

    • Large subunit catalyzes peptide bond formation

    • E, P, and A sites accommodate tRNA binding and peptide elongation

  • The genetic code is read in triplets (codons) on mRNA; redundancy (degeneracy) means multiple codons can code for the same amino acid

Key Takeaways and Connections

  • Gene expression relies on a tightly regulated flow of information: DNA -> RNA (transcription) -> protein (translation) -> functional protein activities

  • The noncoding DNA fraction plays roles in chromosome structure and regulation of gene expression, not just “junk” DNA

  • DNA replication requires high fidelity; errors can lead to mutations with diverse outcomes, including hereditary diseases or cancer

  • The cell cycle coordinates growth, DNA replication, and division; checkpoints ensure proper replication and division

  • Chromosome structure (chromatin) changes dynamically with cellular needs; packaging enables enormous lengths of DNA to fit inside the nucleus

  • Diseases like sickle-cell disease and cancer illustrate how single genes or genetic alterations can have profound physiological consequences

  • Understanding protein synthesis, posttranslational modification, and intracellular trafficking (ER and Golgi) explains how genetic information becomes functional, secreted, or membrane-bound proteins

Quick Reference Numbers and Key Facts (for memorization)

  • Chromosomes in a human nucleus: 46 DNA molecules

  • Average length of a human DNA molecule: 2\text{ inches} when extended

  • Coding vs noncoding DNA: 2\% coding, 98\% noncoding

  • Estimated human genes: about 20{,}000 (though some sources cite up to 30{,}000-35{,}000 depending on annotation)

  • Base pairing hydrogen bonds: A-T: 2; G-C: 3

  • Chromatin organization: DNA length \approx 2\text{ m}; nucleosome diameter \approx 11\text{ nm}; 30 nm fiber; 700 nm chromatid condensation

  • Cell cycle phases durations (illustrative): S-phase typical DNA replication time ~6-8\text{ hours}; G2 preparation ~4-6\text{ hours}; Interphase overall variable

  • Diploid vs haploid: 2n=46 in somatic cells; haploid n=23 in germ cells

  • Start codon: AUG; Stop codons: UAG, UGA, UAA

  • Typical number of amino acids in a protein is determined by the length of the mRNA coding region and reading frame; protein folding and posttranslational modifications are essential for function