Anatomy and Physiology 12 - DNA, RNA, and Replication

Historical Discovery of DNA as Genetic Material

• The identification of DNA as the primary genetic material was the culmination of several decades of scientific research.

• Frederick Griffith (Late 1920s): Griffith's experiments identified a "transforming substance." He observed that this substance possessed the capability to change nonlethal bacteria into lethal bacteria, a process known as transformation.

• Alfred Hershey and Martha Chase (Early 1950s): This team firmly established DNA, rather than protein, as the genetic material.

  • They utilized the T phage, a virus that infects bacteria to replicate itself.

  • Experiment 1 (Radioactive DNA): Viruses with radioactive DNA were used to infect bacteria. After infection, the researchers identified that the radioactivity had entered the bacterial cells.

  • Experiment 2 (Radioactive Protein): Viruses with radioactive protein were used to infect bacteria. Radioactivity was not found inside the bacterial cells after infection.

  • Conclusion: Because only the radioactive DNA entered the cells to direct the production of new viruses, it was concluded that the hereditary material is DNA.

Functions and Biological Importance of DNA

• Definition: DNA stands for Deoxyribonucleic acid. It serves as the genetic material and the primary control molecule of life.

• Major Functions of DNA:

1. Control of Cellular Activities: DNA governs all cellular processes, including reproduction. It carries a genetic CODE, which is encoded in the specific sequence of nitrogenous bases strung together. In sexual reproduction, DNA from the male and female combine to form the genetic blueprint of the offspring.

2. Self-Replication: DNA makes exact copies of itself through a process called replication, ensuring genetic information is passed accurately to new cells.

3. Source of Diversity and Evolution: DNA undergoes mutations. These structural or numerical changes, along with recombinations, are the fundamental source of life's diversity. Evolution proceeds from the level of DNA; varying combinations resulting from mutations and sexual reproduction explain the existence of all species throughout Earth's history.

• Unity of Life: Many biologists believe life began as a nucleic acid. While there are two types—DNA and RNA—the first form of life is theorized to have been a self-replicating strand of RNA.

Structural Characteristics of DNA

• Nucleotide Composition: DNA is a polymer composed of a chain of nucleotides. Each nucleotide consists of:

  • A phosphate group.

  • A deoxyribose sugar.

  • A nitrogen-containing base.

• Nitrogenous Bases: There are four bases categorized into two types:

  • Purines: Adenine ($A$) and Guanine ($G$).

  • Pyrimidines: Cytosine ($C$) and Thymine ($T$).

• The Double Helix Structure:

  • The DNA molecule consists of two strands that twist around each other to form a double helix.

  • The backbone of the strands consists of alternating phosphate and sugar molecules.

  • The two strands are held together by hydrogen bonds between complementary base pairs on opposite strands.

  • Complementary Base Pairing: Adenine always pairs with Thymine ($A-T$) and Guanine always pairs with Cytosine ($G-C$).

Scale and Variation in DNA

• Physical Dimensions: DNA strands are extremely long, containing millions of atoms. A single human cell contains approximately $1\,m$ of DNA.

• Base Pair Count: There are approximately $4 \times 10^9$ (4 billion) pairs of bases in a human cell.

• Genetic Variation: Only about $3 \times 10^6$ (3 million) base pairs—which is only $0.1\%$ or one-tenth of $1\%$ of our total DNA—are responsible for the physical differences and diverse characteristics among individual humans.

Genes and Chromosomes

• Genes: These are the units of inheritance that control the characteristics and capabilities of an organism. They are located on chromosomes within the cell nucleus.

• Gene Composition: A gene is a segment of DNA consisting of a sequence of approximately $1000$ DNA base pairs, though this length varies considerably.

• Chromosome Scale: According to the provided material, approximately $175,000$ genes compose the DNA molecule of a single human chromosome.

• Function of Genes: Genes act in pairs to dictate traits and control cellular chemical reactions by directing the formation of enzymes.

• Inheritance: Genes occur in pairs; an individual receives half from their mother and half from their father. Most phenotypic characteristics, such as height and eye color, are polygenic (determined by combinations of several genes).

Statistics of Chromosome Numbers Across Species

• Animals:

  • Fruit fly: $8$

  • Guinea Pig: $16$

  • Dove: $16$

  • Snail: $24$

  • Earthworm: $36$

  • Tibetan fox: $36$

  • Cat: $38$

  • Pig: $38$

  • Mouse: $40$

  • Rat: $42$

  • Syrian hamster: $44$

  • Rabbit: $44$

  • Hare: $46$

  • Human: $46$

  • Ape: $48$

  • Sheep: $54$

  • Elephant: $56$

  • Cow: $60$

  • Donkey: $62$

  • Horse: $64$

  • Dog: $78$

  • Chicken: $78$

  • Carp: $104$

  • Butterflies: $380$

• Plants:

  • Arabidopsis: $10$

  • Rye: $14$

  • Einkorn wheat: $14$

  • Maize: $20$

  • Wild tobacco: $24$

  • Pollard wheat: $28$

  • Bread wheat: $42$

  • Cultivated tobacco: $48$

  • Fern: $1200$

Genetic Mapping and Sex Chromosomes

• Karyotyping: The process of organizing and visualizing an organism's chromosomes.

• Sex Chromosomes: Humans possess $X$ and $Y$ chromosomes.

• Map of Chromosome X (Associated Disorders):

  • Ichthyosis (X-linked).

  • Hypophosphatemia.

  • Ocular albinism.

  • Duchenne muscular dystrophy.

  • Retinitis pigmentosa.

  • Lesch-Nyhan syndrome.

  • Hemophilia B.

  • Fragile X syndrome.

  • Hemophilia A.

  • Color blindness (several forms).

  • Spastic paraplegia (X-linked).

• Map of Chromosome Y (Identified Loci):

  • Testis Determining Factor (TDF).

  • Gadgetry (MAC-locus).

  • Channel Flipping (FLP).

  • Catching & Throwing (BLZ-1).

  • Self-confidence (BLZ-2) (Note: unlinked to ability).

  • Ability to Remember & Tell Jokes (GOT-1).

  • Sports Page (BUD-E).

  • Addiction to death & destruction movies (T-2).

  • Air Guitar (RIF).

  • Ability to identify aircraft (DC10).

  • Preadolescent fascination with Arachnida & Reptilia (MOM-4U).

  • Spitting (P2E).

  • Sitting on the john reading (SIT).

  • Inability to express affection over the phone (ME-2).

  • Selective hearing loss (HUH?).

  • Total lack of recall for dates (OOPS).

The Mechanism of DNA Replication

• Purpose: To provide a copy of DNA for each new cell during division. Replication results in the copying of one double helix into two identical double helices.

• Semi-Conservative Nature: Each new double helix consists of one original parental strand and one newly synthesized daughter strand.

• Molecular Process and Enzymes:

1. DNA Helicase: This enzyme separates the DNA strands by breaking the hydrogen bonds between bases, "unzipping" the helix.

2. Primase: Involved in the initiation of synthesis (mentioned as part of the Amoeba Sisters visual context).

3. DNA Polymerase: Catalyzes the incorporation of new nucleotides by complementary base pairing.

• Directionality: DNA polymerase can only add nucleotides to one end of the growing chain.

• Leading Strand: Synthesis is continuous and follows the direction of the helicase enzyme.

• Lagging Strand: Synthesis is discontinuous, resulting in the formation of Okazaki fragments.

1. DNA Ligase: This enzyme connects the Okazaki fragments and seals any breaks in the sugar-phosphate backbone, ensuring a continuous strand.

Ribonucleic Acid (RNA)

• Function: RNA (Ribonucleic acid) is the mechanism by which DNA communicates its message. It is necessary in all organisms for protein synthesis and acts as the genetic material for some viruses.

• Evolutionary Context: RNA is theorized to be the original nucleic acid, potentially arising $3.8 \times 10^9$ (3.8 billion) years ago.

• Structure of RNA:

  • Sugar: Ribose (contains a hydroxyl group on the $2'$ carbon where deoxyribose has a hydrogen).

  • Bases: RNA uses Uracil ($U$) instead of Thymine ($T$). It also contains Adenine, Guanine, and Cytosine.

  • Strands: RNA is single-stranded and does not form a double helix.

  • Length: RNA is much shorter than DNA.

• Synthesis: RNA is produced from DNA through a process called Transcription.

Comparison Summary: DNA vs. RNA