"The function of an ideal is not to be realized but, like that of the North Star, to serve as a guiding point." --Edward Abbey

I. Now what?

1. We know that genes are carried on chromosomes. . . but what are chromosomes, and how do they do what they do?
2. By the 1860s, biochemists had described some large molecules from the nucleus, which were named nucleic acids.
   1. Chromosomes are basically made up of nucleic acids and proteins.
   2. Nucleic acids are extremely long, ropy molecules -- the reason that you can't see chromosomes except at cell division is that, during division, the nucleic acids are tightly wrapped around a protein core, making a very compact mass. During interphase, the chromosomes are "unwrapped" and therefore not distinctly visible.
3. Frederick Griffith's experiments on the bacteria that cause pneumonia, published in 1928, showed that there was a "transforming principle" that could be passed from cell to cell -- even from a dead cell to a live one.
4. Work led by Oswald Avery, involving purifying and testing various extracts of bacteria, established that a particular nucleic acid called DNA (short for deoxyribonucleic acid) was this "transforming principle."

1. First, a bit about monomers and polymers. . .
   1. A very common situation: One type of simple molecule, or a group of simple molecules, are strung together in a chain or branched chain.
   2. Think of a train. There may be only a few types of cars (locomotive, boxcar, tank car, refrigerated car, flatcar, sleeper, diner, caboose. . . ). But by arranging these in different orders, you can make trains of almost any length that will carry virtuallly anything.
   3. A complex molecule made up of simpler units is a polymer. . .
   4. and the simpler subunits are known as monomers. When monomers join together to form a polymer, we say that they polymerize.
2. By 1935 or so, the biochemists P. Levene and E. Chargaff had worked out what DNA was made of:
   1. DNA is a polymer made up of many smaller monomers called nucleotides. Each nucleotide has three parts: a sugar, a phosphate group, and a single-ring or double-ring molecule containing carbon and nitrogen, known as the base.
      
      A typical nucleotide, with adenine as the base

   2. DNA is made up of four types of nucleotides, each with a different base. They are: adenine, thymine, guanine, and cytosine, abbreviated A, T, G, C.

      
      The "Fab Four" DNA nucleotide bases

   3. Chargaff noticed something odd: the amount of A always equalled the amount of T, and the amount of G always equalled the anount of C. This is Chargaff's Rule: A=T and G=C. (What's more, A+G = C+T -- and, of course, A+C = G+T).
   4. Even odder, different organisms turned out to have different DNA compositions. For instance: your DNA is almost exactly 40% G + C, while some bacteria have DNA that's over 70% G + C. Hmm. . .
   
   Rosalind Franklin

3. Maurice Wilkins's research team at Cambridge University in England -- including Rosalind Franklin -- had used X-ray crystallography to get data on how DNA was shaped. They discovered that it must be a helix -- a coil or twist of some sort.
4. Francis Crick and James Watson, in 1953, put together X-ray crystallography data with data on chemical composition, and worked out what the structure of the DNA molecule must be. (You can read the text of their historic article, published in the journal Nature on April 2, 1953, by clicking here.)
   The famous "double helix". On the left, a still picture of a short piece of DNA. On the right, an animation of a rotating molecule (may not be viewable with all browsers).
   1. The sugars and phosphates of nucleotides link together to form the red-and-white spirals you can see. The bases (blue-and-white) fit in between the sugar-phosphate "backbones". The whole molecule may consist of millions and millions of nucleotides. A single human chromosome -- remember those? -- would be roughly an inch long (but only eighty billionths of an inch wide) if you could stretch it out fully.
   2. Here's a different picture. (If you could somehow enlarge a typical eukaryote chromosome to the size of this picture, the molecule would stretch from here to Washington DC!) For clarity, the sugar-phosphate "backbone" is drawn as a simple ribbonlike shape. You can see how the bases form "rungs" linking the two sugar-phosphate chains together. The hydrogen bonds are represented as rows of dots, and the whole thing looks like a twisted ladder, or a spiral staircase:
      
      A short length of DNA

   3. Let's "untwist" the helix for a moment. If you could do that, here's what you'd see:
      
      An "untwisted" short length of DNA
      1. The sugars and phosphates are seen forming the sides of the "ladder."
      2. Hydrogen bonds between the bases hold the two strands of the helix together.
      3. Because of the shapes of the bases, however, A will only form hydrogen bonds with T, and G will only form hydrogen bonds with C. If one strand of a DNA helix has the base sequence, say, AAGCGAT, the other must be TTCGCTA, or the helix won't stay together. Now Chargaff's Rule makes sense!
   4. Because of complementarity, replicating DNA is fairly simple.
      1. The two strands of a DNA molecule are related to each other like a sculpture and its mold, or like a photo and its negative -- if you have one, you know exactly what the other one must be, and you can replicate one from the other.
      2. A DNA molecule "unzips" down the middle, breaking the hydrogen bonds.
      3. Free nucleotides are then fit onto each "unzipped" strand, and "welded" together into a new strand. Each old strand serves as a template for the new strand.

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