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Samford University -- Department of Biological and Environmental Sciences
Genetics -- Biol 333

DNA
Nucleic acids "will perhaps deserve equal consideration with the proteins."
-- F. Miescher,  1871
The Discovery of Nucleic Acids: In 1868, Friedrich Miescher isolated a new substance from nuclei of cells from hospital bandages. He realized that this material, which he called nuclein, was a new class of organic material. It contained C, H, and O (like all organics), plus N (like the proteins). However, he knew it was not protein since it had no S and also had P. Furthermore, pepsin, which digests proteins, had no effect on nuclein. The nuclein Miescher isolated was probably a mixture of DNA and RNA. Today, instead of nuclein, we call this class of organic chemical the nucleic acids.
DNA Is the Genetic Material (of almost everything): In 1944, Avery, MacLeod, and McCarty showed that DNA was the genetic material of a bacterium (Streptococcus pneumoniae) that causes a type of pneumonia in mice. This experiment was based on the 1928 experiment of Griffith where he showed that some substance from dead IIIS bacteria (S cells have a capsule) could transform live IIR bacteria (R cells lack a capsule) into live IIIS cells. Avery et al. showed that Griffith's "transforming principle" was IIIS DNA. (A 1952 experiment by Hershey and Chase with the phage T2 showed that this virus' genetic material was DNA. Some DNA viruses have single-stranded DNA and some have double-stranded DNA.) Mutagenesis experiments also indicated that DNA was the genetic material of eukaryotes (this was later proved directly).

RNA Is the Genetic Material of Some Viruses. Some viruses have no DNA in the virus particle, but do have RNA. In these viruses, the RNA (which may be single stranded or double stranded) is the genetic material. Some RNA viruses replicate their RNA (similarly to the way DNA is replicated but using RNA replicase) while others use the enzyme reverse transcriptase to make a DNA intermediate which is then copied into new RNA. These viruses are called retroviruses.

DNA Structure: DNA is a polynucleotide (polymer of nucleotides). (Arsenic-based life finding fails follow-up)

 
  • The DNA Polynucleotide: The DNA polynucleotide is made by joining many nucleotides together. The bond is a phosphodiester bond between the 5' carbon of one deoxyribose and the 3' carbon of the next deoxyribose. Therefore, a single strand of DNA has a sugar-phosphate backbone with the bases protruding off to one side. Any order of the bases is possible along one strand.
    • Nucleotide: Each DNA (or RNA) nucleotide is composed of three subunits. (A nucleotide = phosphate + pentose + base; a nucleoside = pentose + base.)
      • Phosphate: A phosphate group (PO4--) is attached to the 5' carbon of deoxyribose. DNA is negatively charged because of the phosphates (there is only one negative charge after the phosphate links two nucleotides together).

 
      • Pentose: Deoxyribose is a pentose sugar. Its carbons are numbered and given the prime (') designation to distinguish them from the carbons of the nitrogen bases. Deoxyribose is actually 2'-deoxyribose (RNA's ribose that has lost an oxygen atom from the 2' carbon).
      • Nitrogen Bases: A nitrogen base is attached to the 1' carbon of deoxyribose. The nitrogen found in DNA is in the bases. There are four possible bases divided into two types.
        • Purines: Purine bases have a double ring structure and are larger than pyrimidines. There are two purines in DNA. Purines are attached by their position 9 nitrogen to the 1' carbon of deoxyribose. The purines of DNA are adenine and guanine.
        • Pyrimidines: Pyrimidines have a single ring structure and are smaller than purines. There are two pyrimidines in DNA. Pyrimidines are attached by their position 1 nitrogen to the 1' carbon of deoxyribose. The pyrimidines of DNA are cytosine and thymine. (Uracil replaces thymine in RNA.)
    • The Double Helix: In 1953, Watson and Crick proposed a 3-dimensional model for the structure of DNA: the double helix. Their work was based on the X-ray crystallography (X-ray diffraction) work of Franklin and Wilkins, on the work of Chargaff (Chargaff's Rules: A=T, G=C), and on a general understanding of the structure of the DNA polynucleotide (the information above). Their research was primarily model building and won them, along with Wilkins, the 1962 Nobel Prize. Here are the highlights of their model. (1953 article)

      • DNA has two, antiparallel strands: DNA has two polynucleotides running in opposite polarity.
      • Alpha-helix: The two strands are coiled in an alpha-helix (right-handed helix).
  • Specific Base Pairing: Base pairing holds an A of one strand to a T of the other strand and a G of one strand to a C of the other strand. This base pairing is by hydrogen bonding involving N, O, and H. There are three bonds that hold guanine to cytosine and two that hold adenine to thymine. (PBS video).
    • The Dimensions of the Double Helix: The bases are 3.4 Å thick and stacked internally (i.e., the "distance between the bases" is 3.4 Å). The width of the molecule is 20 Å and it makes one complete turn (360º) every 34 Å of length. There are 10 base pairs per turn of the helix. (3-D DNA Viewer)(DNA)

Things I Learned at the Movies:
The Eiffel Tower can be seen from any window in Paris.