DNA as Hereditary Molecule

• Before DNA knowledge, evolution and heredity processes lacked clarity.

Establishing DNA as the Hereditary Molecule

• Scientists aimed to understand how organisms produce similar offspring.
• The origin of DNA was initially unknown.
• Darwin's heredity concept faced challenges due to blending inheritance, where offspring phenotypes appear intermediate between parents.
• Mendelian inheritance patterns lacked a physical or molecular explanation.
• Mendel's work, rediscovered in the 1900s, showed traits are passed predictably but lacked a mechanism.
• Mendel demonstrated particulate inheritance, including the laws of dominance, segregation, and independent assortment.
• He demonstrated traits are inherited in quantifiable, predictable combinations.
• Genes occur in pairs as dominant and recessive alleles.
• Offspring randomly receive alleles during gamete formation/meiosis.
• Allele distribution into cells occurs randomly.
• Mendel could predict traits through ratios but didn't know the mechanisms behind this.
• Scientists proposed that chromosomes are responsible for inheritance long before the mechanism was clear.

Chromosomes and Heredity

• Theodor Boveri found proper sea urchin embryo development to be dependent on chromosomes.
• Walter Sutton described chromosome division during meiosis in grasshopper testes.
• Morgan and the "Fly room people" established chromosomes as the physical structures for heredity.
• Eye color mutations in flies followed the X chromosome distribution.
• Changes in observable traits depend on the X chromosome state.
• They concluded that chromosomes carry hereditary information, explored further to get to DNA.
• The one gene–one polypeptide hypothesis stated: Beadle and Tatum worked on mold showing gene mutations affect enzymes to use amino acids, genes directing protein synthesis.
• Neurospora crassa wild-type spores were exposed to x-rays to produce mutagenized spores and regular wild-type spores.
• Mutant spores were cross-bred with wild-type spores.
• Mutants were grown in complete media (with amino acids) and minimal media (without amino acids), looking for mutants growing in complete media.
• Spores unable to grow on a minimal medium are tested on a minimal medium with a single amino acid added.
• Spores that grew in only one tube have a pathway mutation producing that amino acid.
• Mutants that grew in arginine had a mutation in arginine metabolism.
• This showed that genes are needed to make proteins.
• Genes were on chromosomes and directed protein synthesis, but the gene's biochemical identity remained unknown.
• Chromosomes contain DNA and protein, raising the question of which carries heredity.
• Geneticists speculated needed be stable yet capable of mutation for evolution.
• People thought it was protein since it had many amino acids.
• Griffith discovered that a chemical substance could transfer from non-living cells to living cells, causing the living cell to show characteristics of the non-living cell.
• Griffith worked with smooth (S) and rough (R) strains of Streptococcus pneumoniae
• S cells are virulent, R cells are not.
• Mice injected with dead S cells and living R cells died
• Living S cells recovered, indicating gene transfer.
• Something in dead S cells transformed R cells into the virulent strain.
• Avery showed; removing DNA stopped R cells' change to S cells, proving DNA carries the "transforming principle."
• Cells are boiled to kill them, then homogenized to release their contents
• Cells are centrifuged, with bacteria at the bottom of the tube were retained and the top portion was discarded
• Treatment with protease didn't stop the transfer of genes; active factor isn't protein
• Treatment with ribonuclease didn't stop the transformation; active factor isn't RNA
• Treatment with deoxyribonuclease stopped R cells from transforming, showing that the active factor is DNA.
• Genes are hereditary thanks to DNA.
• Hershey & Chase found that the T2 virus has DNA and protein.
• Infected cells contained only DNA, meaning it carries genetic information, and the protein coat serves only as a shell.
• The blender experiment further proved this.
• Bacteriophages have a protein coat protecting nucleic acid (DNA or RNA).
• Researchers radiolabeled the bacteriophage's protein coat and internal DNA.
• Radioactive sulfur only binds to protein & P only to DNA.
• Viruses discard its protein coat, and the DNA uses ribosomes to direct viral production.
• Sulfur stayed in viral coat liquid, discarded after infection
• Phosphorus inside bacteria meant DNA entered cells.
• Protein doesn't impact virus creation nor contain genetic material.
• This discovery was a matter of chance, depending on the virus being studied.
• DNA in chromosomes wasproven to be the carrier of genetic information.
• How it functions depended on its unknown structure.
• DNA is the molecular gene carrier.

Discovering the Structure of DNA

• DNA's structure was revealed through combined work and x-ray crystallography data.
• Watson and Crick discovered DNA's double helix structure.
• Franklin used x-ray crystallography, and Watson used her data unknowingly for their conclusions.
• DNA structure revealed a copying mechanism, explaining Mendel's observations: "specific pairing suggests a copying mechanism."
• DNA's double helix is necessary for its replication.
• Each DNA strand can create copies for DNA creation during cell division.
• Complementarity ensures strands replicate in a semi-conservative manner.
• New copies have one original and one new strand.
• This mechanism explained how cells copy and pass down DNA.