MBG LECTURE NOTES: DR. BAKER’S LECTURES Chapter 9: DNA and the Molecular Structure of ChromosomesBrief History of Molecular Genetics:-1869: Miescher isolates DNA (the discovery of nuclein)-1944: Avery and coworkers show DNA = genetic material (identified DNA as the “transforming principle”) -1953: Watson and Crick publish double helix structure giving rise to the central dogma (based on two major kinds of evidence: A=T and C=G therefore fixed interrelationship. Also, X-ray diffraction patterns indicate that DNA was a highly ordered, two-stranded structure with repeating substructures spaced every 0.34 nanometer along the axis of the molecule). (Wilkins also involved). Franklin: X-ray diffraction photo of DNA-1952: Alfred Hershey and Martha Chase: studies of virus infection of bacterial cells. They showed that only the DNA of a virus needs to enter a bacterium to infect it. Their experiment provided strong support for the idea that genes are made of DNA. They firmly restated the conclusion that Avery had proposed. Mostly labeled (radioactive particle allows it to be traced) DNA (less so protein) was taken up by the bacterial cells. Suggested DNA directs production of more virus progeny after bacterial infection. -50s-60s: Basic enzymology for gene expression-70s: DNA cloning, recombinant DNA and DNA sequencing-80s: PCR and RNA world-90s: genome programs and proteomics-2000s: Interactomes (the whole set of molecular interactions in cells)Automated DNA sequencing makes it possible to sequence many human genomes quickly. The goal of the 1000 genomes project is to find most genetic variants that have frequencies of at least 1% in the populations studied. In 1869, Friedrich Miescher isolated DNA for the first time. A nucleotide contains a nitrogen-containing base, a phosphate group, and a sugar. Nucleic acids are composed of repeating subunits called nucleotides. Each nucleotide is composed of three units. The phosphate group forms a covalent phosphodiester bond between adjacent nucleotides. Strong acid group: represents major charge (-) at biological (neutral) pH ranges. The 5-carbon sugar or pentose will either be ribose (in RNA) or deoxyribose (in DNA). The difference between the two is that deoxyribose has one less oxygen (meaning one less hydroxyl group. The hydrogen containing base in each one will be one of adenine, guanine (purines), cytosine, thymine, or uracil (pyrimidines). Structure of a polynucleotide or DNA chain: adjacent nucleotides are joined by phosphodiester bones, that join the 3’-OH of one sugar to the 5’-OH of an adjacent sugar. This gives the DNA chain its “polarity”.