BIO273 Biology - History of DNA PDF

BIO273 Biology History of DNA Nuclein Johann Miescher (1869)  Wanted to identify the composition of the nucleus  Collected cells with very little cytoplasm fish sperm & white-blood cells from pus-filled bandages  Isolated unique large acidic molecules from the nuclei He called...

BIO273 Biology History of DNA Nuclein Johann Miescher (1869)  Wanted to identify the composition of the nucleus  Collected cells with very little cytoplasm fish sperm & white-blood cells from pus-filled bandages  Isolated unique large acidic molecules from the nuclei He called it “Nuclein” Rich in nitrogen & phosphorus  Conclusion The Nucleus contains “Nuclein”, a large acidic molecule  Prior to this, protein believed to be the hereditary material SCHOOL OF BIOLOGICAL SCIENCES 2 AND APPLIED CHEMISTRY Chromosomes Walther Flemming (1878)  Observed thread-like structures in the Nucleus They strongly absorb basophilic aniline dyes Named them “Chromatin”  Chromosomes means “coloured bodies”  Cells stained at different stages of cell division Observed sequence of changes in the nucleus during cell division Threads shortened, split longitudinally into two halves & move to opposite side of the cell. Named this process “Mitosis” (Greek for “thread”) SCHOOL OF BIOLOGICAL SCIENCES 3 AND APPLIED CHEMISTRY Nucleic Acids Albrecht Kossel (1881)  Identified Nuclein as a nucleic acid Name it Deoxyribonucleic acid (DNA)  Identified the five nucleotides Adenine (A), Cytosine (C), Guanine (G), Thymine (T) & Uracil (U)  Rewarded the 1910 Nobel Prize in Physiology or Medicine SCHOOL OF BIOLOGICAL SCIENCES 4 AND APPLIED CHEMISTRY Chromosomes Walter Sutton & Theodor Boveri (1902) Came to same conclusion independently  Boveri using Roundworms Chromosomes must be present for proper development  Sutton using Grasshoppers Chromosomes occurred in matched pairs of maternal & paternal chromosomes, which separate during Meiosis  Conclusion Chromosomes are the carrier of hereditary material SCHOOL OF BIOLOGICAL SCIENCES 5 AND APPLIED CHEMISTRY Walter Suttons 1902 Paper Closing Statement  Chromosomes contain genetic material  Chromosomes are passed along from parent to offspring  Chromosomes are found in pairs in the nucleus of most cells  During the formation of sperm & egg cells in men & women, respectively, chromosomes separate  Each parent contributes on set of chromosomes to it’s offspring SCHOOL OF BIOLOGICAL SCIENCES 6 AND APPLIED CHEMISTRY Discovery of DNA Function Fred Griffith (1928)  1918 Spanish flu pandemic caused by H1N1 virus 30% of world infected; 20 – 100 million deaths  Streptococcus pneumoniae bacteria potential next pandemic  Griffith attempting to create a vaccine Vaccine is a killed or weaken bacteria Mobilize the immune system against a real attack  Streptococcus pneumoniae has two strains Rough (R) appearance - has no capsule - destroyed by immune system Smooth (S) appearance - is more virulent as capsule prevents detection SCHOOL OF BIOLOGICAL SCIENCES 7 AND APPLIED CHEMISTRY Griffith Experiment (1928)  Inject mice with R strain R  Inject mice with S strain S Mice survive Mice died Live R cells in their blood Live S cells in their blood  Conclusion  Conclusion R strain is harmless S strain is deadly SCHOOL OF BIOLOGICAL SCIENCES 8 AND APPLIED CHEMISTRY Griffith Experiment (1928)  Heat-inactivation is common for vaccine production  Inject mice with heat-inactivated S strain S Mice survive No Live S cells in their blood  Conclusion Heat-inactivation kills the S strain SCHOOL OF BIOLOGICAL SCIENCES AND APPLIED CHEMISTRY Griffith Experiment (1928)  Inject mice with both inactivated S strain & Live R strain Mice died S + R Live R & S cells in their blood  Conclusion Hereditary material from S cells was picked up by the R cells R Strain cells had been “transformed” into S Strain cells What happened? S Strain DNA survived the heating process Gene for protective capsule was taken up by some of R cells The R Strain could now go undetected by immune system SCHOOL OF BIOLOGICAL SCIENCES AND APPLIED CHEMISTRY Discovery of DNA Function Oswald Avery (1944)  Continued with Griffith’s research  Created liquid extract of S cells (killers) Contained proteins, lipids & nucleic acids  Treated R cell (harmless) with S extract R cells became deadly Transformation R cells acquired something from the S cells  Conclusion Something in the extract caused the transformation SCHOOL OF BIOLOGICAL SCIENCES 11 AND APPLIED CHEMISTRY Avery Experiment (1944)  Added Protease, Lipase or RNase to extract Degrades Proteins, Lipids & RNA Treated R cells with extract R cells still became deadly S cells (transformation)  Added DNase to the extract Degrades DNA Treated R cells with extract No deadly S cells created No transformation  Conclusion DNA must be what is transforming the cells SCHOOL OF BIOLOGICAL SCIENCES 12 AND APPLIED CHEMISTRY Discover of DNA Function  Alfred Hershey & Martha Chase (1952)  Many still believed Proteins hereditary material DNA appeared to be an inert molecule Phosphorus storage  Bacteriophage Virus that infects bacteria Hereditary material enters bacterial cell “Body” of the virus stays outside the cell  Consists of DNA & Proteins What is entering the bacteria? SCHOOL OF BIOLOGICAL SCIENCES 13 AND APPLIED CHEMISTRY Hershey & Chase (1952)  Viruses can only replicate inside a living cell  Use host cell’s enzymes and raw materials to make new cells  Phages can be labeled by growing them in bacteria that has radioactive raw materials  Grow bacteria in 35S  Grow bacteria in 32P S (sulfur) is only in amino acids P (phosphorus) is only in nucleotides Infect bacteria with phage Infect bacteria with phage Phage that replicate inside will Phage that replicate inside will have have radioactive Proteins radioactive DNA SCHOOL OF BIOLOGICAL SCIENCES 14 AND APPLIED CHEMISTRY Hershey & Chase (1952)  Infect non-radioactive bacteria with 35S phage Phage inject their hereditary material into the bacteria  After infection, separate the bacteria from the phage  Tested each for the 35S Radioactivity was found in the phage No radioactivity in the bacteria  Conclusion Phage proteins are not injected into bacteria SCHOOL OF BIOLOGICAL SCIENCES 15 AND APPLIED CHEMISTRY Hershey & Chase (1952)  Infect non-radioactive bacteria with 32P phage Phage inject their hereditary material into the bacteria  After infection, separated the bacteria from the empty phage  Tested each for the 32P No radioactivity in the phage Radioactivity was found in the bacteria  Conclusion Phage DNA was injected into bacteria Therefore, DNA is the hereditary material SCHOOL OF BIOLOGICAL SCIENCES 16 AND APPLIED CHEMISTRY Summary  Nucleic acids are found in the Nucleus as thread-like Chromosomes  Nucleic acid DNA (Deoxyribonucleic acid) contains the hereditary material  DNA has information that can transform bacteria  DNA is what viruses use to transfer information to their host  Only after the Hershey & Chase experience was DNA accepted, by the scientific community, as the molecule to store the hereditary material SCHOOL OF BIOLOGICAL SCIENCES 17 AND APPLIED CHEMISTRY