Molecular Biology Milestones: DNA, Proteins, and Cellular Function

Posted on Feb 5, 2026 in Biology

Molecular Biology Milestones: DNA Discovery

Identifying DNA as the Hereditary Material

  • Mendel: Hypothesized the existence of “hereditary molecules” (genes) that pass information through generations via his pea plant experiments.
  • Miescher: First to isolate DNA (which he called “nuclein”) from the nuclei of white blood cells found in pus.
  • Hammerling: Used green algae to show that the nucleus contains the genetic information responsible for regeneration.
  • Griffith: Discovered the “transforming principle” while working with Streptococcus bacteria and mice; he found that a substance from dead virulent bacteria could transform live non-virulent bacteria.
  • Avery, McLeod, and McCarty: Built on Griffith’s work; they used enzymes to systematically destroy proteins, RNA, and DNA, proving that DNA was the transforming agent.
  • Hershey and Chase: Used bacteriophages (viruses) labeled with radioactive isotopes (P for DNA, S for protein) to definitively prove that DNA, not protein, enters the cell and acts as the hereditary material.

Clarifying DNA Structure and Function

  • Levene: Discovered the chemical components of DNA: a deoxyribose sugar, a phosphate group, and four nitrogenous bases (A, T, G, C).
  • Chargaff: Discovered the specific base-pairing ratios: the amount of Adenine (A) always equals Thymine (T), and Guanine (G) always equals Cytosine (C).
  • Franklin and Wilkins: Used X-ray crystallography to capture images of DNA, which revealed its size and helical shape.
  • Watson and Crick (1953): Integrated the work of Franklin and Chargaff to build the first accurate 3D model: the double helix structure, anti-parallel sugar-phosphate backbones, with nitrogenous bases on the interior held by hydrogen bonds (2 for A-T; 3 for G-C).
  • Meselson and Stahl: Later confirmed Watson and Crick’s hypothesis that DNA replicates via a semi-conservative mechanism using nitrogen isotopes, helping biologists resolve the question of how DNA replication works.

Linking Genes to Proteins and Biotechnology

  • Garrod: Hypothesized that “inborn errors of metabolism” were due to the lack of specific enzymes.
  • Beadle and Tatum: Worked with bread mold to establish the “one gene, one enzyme” hypothesis.
  • Ingram: Studied Sickle-cell disease to show that a gene specifies the exact amino acid sequence in a polypeptide chain.
  • Cohen and Boyer (1973): Collaborated to create the first recombinant DNA. They “spliced” DNA from one organism into a bacterial plasmid, creating the first genetically modified organism (GMO). This launched the biotechnology industry (founding Genentech) and made it possible to mass-produce human insulin in bacteria.
  • Frederick Sanger (1977): Developed the “Sanger Sequencing” method. This allowed scientists to read the exact linear order of nucleotides (A, T, G, C) for the first time. Used this technique to sequence the first full genome (a virus) and laid the groundwork for the Human Genome Project and modern genetics.

The Unique Role of Proteins for Life

Proteins are the most diverse macromolecules in terms of function. They are often called the “workhorses” of the cell because they perform almost every task required for life:

  • Enzymatic Activity: Catalyzing (speeding up) biochemical reactions (e.g., Amylase in digestion).
  • Structural Support: Providing physical framework (e.g., Collagen in skin, Keratin in hair).
  • Transport: Moving molecules across membranes or throughout the body (e.g., Hemoglobin carrying oxygen).
  • Signaling: Acting as chemical messengers (e.g., Insulin regulating blood sugar).
  • Defense: Protecting the body from pathogens (e.g., Antibodies).
  • Movement: Enabling muscle contraction and cellular motion (e.g., Actin and Myosin).

Levels of Protein Structure

Primary Structure

Definition: The unique linear sequence of amino acids in a polypeptide chain. Bonding: Held together by covalent peptide bonds. Significance: This sequence is determined by DNA. Even a single change (mutation) can alter the entire protein’s function (e.g., Sickle Cell Anemia).

Secondary Structure

Definition: Local folding or coiling of the polypeptide backbone. Bonding: Maintained by hydrogen bonds between the oxygen of a carboxyl group and the hydrogen of an amino group. Common Types: Alpha helix (a delicate coil) and beta-pleated sheet (two or more segments of the chain lying side-by-side).

Tertiary Structure

Definition: The overall three-dimensional shape of a single polypeptide. Bonding: Determined by interactions between the R-groups (side chains) of the amino acids. These include: Hydrophobic interactions (non-polar groups cluster in the center), hydrogen bonds, ionic bonds, and disulfide bridges (strong covalent bonds between cysteine amino acids). Significance: This is the level where many proteins become functional.

Quaternary Structure

Definition: The structure formed when two or more polypeptide chains (subunits) aggregate into one functional macromolecule. Examples: Hemoglobin (4 subunits) or Collagen (3 subunits).

Cellular Processes: The Central Dogma

The creation of a protein follows the “Central Dogma” of biology: DNA to RNA to Protein.

Organelles Involved in Protein Synthesis

  • Nucleus: Houses the cell’s genetic material and orchestrates the synthesis of RNA from DNA (Transcription).
  • Ribosomes: Cellular structures responsible for translating genetic code into functional polypeptide chains (Translation).
  • Rough Endoplasmic Reticulum (RER): Facilitates the structural folding and initial chemical modification of newly synthesized proteins destined for secretion or membranes.
  • Golgi Apparatus: Refines, organizes, and encapsulates proteins into vesicles, ensuring they reach their correct biological targets.

Cellular Comparisons: Prokaryotes and Eukaryotes

Fundamental Similarities

Despite their differences, both cell types share essential “machinery” for life:

  • Genetic Material: Both use DNA as their hereditary material and follow the central dogma of biology (DNA to RNA to protein).
  • Cell Membrane: Both are enclosed by a lipid bilayer that regulates the passage of materials.
  • Cytoplasm: Both contain a gel-like substance where metabolic reactions occur.
  • Ribosomes: Both possess ribosomes to synthesize proteins, although their size and structure differ.

Key Differences in Gene Expression and Structure

  • Transcription/Translation Coupling:
    • Prokaryotes (Coupled): Since there is no nuclear membrane, translation can begin before transcription has ceased. Ribosomes attach to the mRNA while it is still being built.
    • Eukaryotes (Separated): Transcription occurs in the nucleus, and the mRNA must be exported to the cytoplasm before translation can begin.
  • Ribosome Size: Eukaryotic ribosomes are significantly larger than prokaryotic ones.
  • Translation Initiation:
    • Prokaryotes: Recognize a specific Shine-Dalgarno sequence on the mRNA.
    • Eukaryotes: Recognize the 5′ cap of the mRNA to begin translation.
  • Starting Amino Acid: In prokaryotes, the starting methionine is tagged with a formyl group (fMet), whereas eukaryotes use regular methionine.
  • Gene Regulation:
    • Prokaryotes: Regulation happens almost exclusively at the transcriptional level, often using operons (clusters of related genes regulated by a single promoter, e.g., the lac operon).
    • Eukaryotes: Utilize extensive post-transcriptional control, including processing pre-mRNA through 5′ capping, 3′ polyadenylation, and alternative splicing. This processing allows mRNA to survive in the cytoplasm and prevents degradation.
  • Chromosomal Structure:
    • Prokaryotes (Circular & Compact): Consist of a single circular chromosome located in the nucleoid, which is small and compact, often containing plasmids.
    • Eukaryotes (Linear & Organized): Multiple linear chromosomes housed in the nucleus, tightly wrapped around histone proteins to manage and condense their large volume of DNA.

Homeostasis: Components of a Biological Feedback Loop

The seven components required for maintaining dynamic equilibrium:

  1. Stimulus: Some change in the external or internal environment that requires a response by the organism.
  2. Monitor (Sensor/Receptor): Detects the stimuli and sends a signal (input) to the coordinating center.
  3. Sensory Pathway: Links the monitor to the coordinating center; carries the signal sent out by the monitor.
  4. Coordinating Center (Integrator): Interprets the message sent by the monitor by comparing the input to a set point; determines what response (output) is required and then sends the appropriate response to a regulator.
  5. Motor Pathway: Links the coordinating center to the regulator; carries the response sent out by the coordinating center.
  6. Regulator (Effector): Makes some sort of response that has the effect of restoring the normal balance.
  7. Response: Some adjustment of the organism that lessens the effect of the stimulus and brings the organism back to dynamic equilibrium.