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The Structure of DNA

First, a Little Bit of History...

Frederick Griffiths (1928)

first reported the mysterious TRANSFORMATION of harmless Pneumococcus bacteria into harmful, pathogenic (disease-causing) (smooth) bacteria in an truly elegant experiment. It was clear that something in the extract of killed smooth bacteria was transforming harmless Pneumococcus into killers. But what could it be? There were several possible candidates: Whatever the culprit, it had to have several properties in order to fit the bill:

Oswald Avery (1944)

demonstrated that the substance responsible for the transformation of harmless bacteria into disease-causing monsters was DNA:

Edwin Chargaff (1950)

  • did chemical analysis of the components of DNA, and noted that the nitrogenous bases (pictured lower down in these notes) Adenine (A) and Thymine (T) were present in approximately equal quantities to each other, as were Guanine (G) and Cytosine (C).
  • This is now known as "Chargaff's Rule"), and it will be explained in just a moment.

    Rosalind Franklin (early 1950's)

    took amazing x-ray crystallographs (a form of microscopic photography) which showed that the mysterious molecule DNA had a spiral shape.

    James Watson and Francis Crick (1953)

    used Franklin's data (not entirely with her consent) to literally cut and paste paper cutouts of the parts of the molecule, and in a stroke of luck and genius, came up with the helical model for which they are so famous today. THEY COULD NOT HAVE DONE IT WITHOUT ROSALIND FRANKLIN'S WORK. But they still get all the credit.

    Let's have a look at the structure of DNA (it looks a little bit like a twisted ladder, in diagrammatic form) and talk a bit about the terminology we use to describe it.

    The nucleic acids DNA (and RNA) are polymers of NUCLEOTIDES.
    A nucleotide is composed of a

    • sugar (deoxyribose in DNA; ribose in RNA)
    • a phosphate group
    • one of four nitrogenous bases:
        The PURINES (composed of two carbon rings):
        • adenine (A)
        • guanine (G)
        The PYRIMIDINES (composed of only one carbon ring):
        • thymine (T)
        • cytosine (C)
        • uracil (U) -- found only in RNA, where it replaces Thymine
    Here's how the DNA molecule is structurally organized. Now you can see what each nitrogenous base actually looks like!

    The nucleotides are linked via special covalent bonds called PHOSPHODIESTER BONDS which join the sugar of one nucleotide to the phosphate of the next. (This region is shown in the black portion of the diagram.)

    The nitrogenous bases forming the "rungs" of the ladder are linked by the weaker HYDROGEN BONDS we've already met. (This region is shwon in the pink portion in the diagram.)

    The structure can also be represented like this. The blue "ribbons" are the

  • sugar-phosphate backbones

    And the colorful "strips" labeled A, T, G or C are the

  • nitrogenous bases.

    ONLY THE NITROGENOUS BASES VARY ALONG THE LENGTH OF THE DNA DOUBLE HELIX. The sugar-phosphate "backbone" remains constant, with the sugars and phosphates all being of the same type.

    YOU CAN NOW SEE CHARGAFF'S RULE EXPLAINED:

    • Guanine binds to Cytosine (G -- C) (via hydrogen bonds)
    • Adenine binds to Thymine (A -- T) (via hydrogen bonds)

    You should also begin to see that there is a message encoded here! The order of the four letters of the DNA "alphabet" can be combined in nearly infinite ways. BUT WHAT ARE THOSE LETTERS SAYING? Stay tuned.

    Note that DNA is a DIRECTIONAL molecule: it has two ends that are not identical, and its two component strands are oriented opposite to each other, running "antiparallel".

    Let's take a look at the numbering system we use to describe this, so that we understand what is meant when we talk about "5' and 3' " ends of the molecule.

    You should now understand what is meant by:
  • nitrogenous base
  • base pair
  • sugar-phosphate "backbone" of DNA

    The GENOME: What is it, and where is it located?

  • PROKARYOTIC GENOME: The genes contained on the bacterial chromosome
      These are the genomes of the true bacteria, and usually (not always) they are present as a single, circular chromosome. This is located in a large clump called the nucleoid (or nucleoid region). This is held together in a live bacterium, but falls apart when the bacterium is lysed (to yield a great, big string of DNA).
  • EUKARYOTIC GENOME:
    • nuclear genome: all the genes on the DNA in the nucleus (autosomes & sex chromosomes)
    • mitochondrial genome: all the genes on the mitochondria chromosome (multiple copies of a single, circular chromosome)
    • chloroplast genome: all the genes on the chloroplast chromosome (multiple copies of a single, circular chromosome)
    Yes, you read that right. Genes are not found only in the nucleus, but also in some very special organelles.

  • So the DNA in eukaryotic cells is found in three very important locations:
    • the nucleus (nuclear genome or nuclear DNA (nucDNA))
    • the mitochondria (mitochondrial genome or mitochondrial DNA (mtDNA))
    • the chloroplasts (chloroplast genome or chloroplast DNA (cpDNA))
    • mitochondrial and chloroplast DNA are sometimes called "organelle DNA"

    THE SIGNIFICANCE OF ORGANELLE DNA

  • In any given cell, the DNA of all mitochondria (or all chloroplasts) is usually identical (not always!).

  • The primary function of organelle DNA is to govern the function of the organelles themselves (mitochondria or chloroplast, whichever holds the DNA in question), and usually encodes the enzymes necessary for the energy transducing reactions (cellular respiration and photosynthesis).

  • Because they are intimately involved in energy transduction, mtDNA and cpDNA can have profound effects on the organism if they mutate. Errors in mtDNA, for example, can result in mitochondrial myopathies which cause profound muscle weakness and other problems.

  • Mitochondria and chloroplasts are always inherited from the mother, and not from the father (except for two species) (a word about "Eve's DNA")

  • Nuclear DNA also participates in manufacturing enzymes for organelle function: the organelles cannot function without nuclear DNA. But the genes in the nucleus and the genes in the organelles are different from one another. THERE IS NO OVERLAP or DUPLICATION between organelle and nuclear DNA.

  • Organelle DNA is remarkably similar to that found in bacteria! It's circular and has many characteristics reminiscent of bacterial DNA.

  • This led Lynn Margulis of Berkeley to hypothesize (1981) that eukaryotic cells may have originated when ancient, small bacteria resembling modern day mitochondria and/or chloroplasts took up residence inside larger bacteria....and stayed! Eventually, because the relationship was mutually beneficial to both the large and the small bacteria (why?), it became permanent, and the Eukaryotic Cell was "born."

  • This idea for the evolutionary origin of Eukaryotic Cells is known as the ENDOSYMBIONT MODEL. We'll hear more about it later.

    THE SIGNIFICANCE OF THE NUCLEAR GENOME:

  • GENES are composed of DNA, which forms the central core of the CHROMOSOME.

  • The physical location of a gene on a chromosome is known as its LOCUS (plural = loci). Sometimes geneticists refer to "gene loci" or simply "loci" when they speak of particular aspects of a gene.

  • THE NUCLEAR GENOME, then, is located in the chromosomes enclosed in the eukaryotic nucleus.

  • Diploid (2n) cells contain two copies of the genome. Haploid (n) cells contain only one copy.

  • n = the number of chromosomes in one complete copy of the genome.

  • HOMOLOGOUS PAIRS of chromosomes are those which carry matching portions (i.e., the same genes), though they may have different alleles. of the genome. Think of them as "mated pairs."

  • Let's take another look at human chromosomes.

    A picture like this is known as a KARYOTYPE. The karyotype yields important information, from chromosome number to physical markers on the chromosomes. THE CHROMOSOMES YOU SEE HERE WERE PHOTOGRAPHED WHEN THEY WERE ALREADY DUPLICATED AND ABOUT TO DIVIDE INTO NEW CELLS. In other words, they are in the midst of the process of chromosome duplication.

    CYTOGENETICS is the study of the physical properties and genetic nature of the chromosomes.

    The c'somes are usually studied while in condensed form, during mitosis. But the landmarks seen in condensed c'somes are assumed to be the same as when the chromosomes exist as diffuse, uncondensed CHROMATIN. (During the part of the cell cycle when the cell is not actively dividing.)

    Useful physical properties of chromosomes include:

    • size (relative to the others in the genome)

    • position of centromere (the slightly constricted area joining two newly duplicated chromosomes)

      • >telocentric (centromere at the end)

      • >acrocentric (centromere very close to the end)

      • >metacentric (centromere in the center)

      • >submetacentric - almost in the center

    Structure of the Eukaryotic Chromosome

  • DNA strand is wound on little "spools" of protein called NUCLEOSOMES.
  • When the DNA/nucleosome strand begins to coil (sort of like a phone cord), it forms a solenoid, a highly coiled strand (like a solenoid cord used to transmit electrical current).

  • The solenoid is "tacked" at SARs (Scaffold Attachment Regions) onto a spiral scaffold protein in big loops.

  • Let's have a look at how the DNA is wound on those little spools called nucleosomes:

  • And then observe how that strand is tacked onto a protein scaffold to form the actual chromosomes structure:

  • The ends of the chromosomes are called TELOMERES. They have special DNA sequences prevent them from being recognized and destroyed by DNA-destroying enzymes in the cell, and they are not at all likely to chemically react with anything. (This will be important to remember for later!) They're a little bit like "caps" on the ends of the chromosomes.
  • When you see me draw lines to represent a chromosome, remember that it's actually this complex, coiled and scaffolded structure that's actually being represented!

    LET'S WATCH A SHORT MOVIE TO DRIVE THIS HOME.