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Molecular Basis of Inheritance

The DNA

Explain the double helix and DNA packaging.

DNA is a long chain (a polymer) of nucleotides. Each nucleotide has three parts: a nitrogenous base, a five-carbon sugar (deoxyribose) and a phosphate. The bases are of two kinds: the purines, adenine (A) and guanine (G), which have two rings; and the pyrimidines, cytosine (C) and thymine (T), which have one. Nucleotides join through 3'-5' phosphodiester bonds between the sugar of one and the phosphate of the next, making a sugar-phosphate backbone with the bases sticking out.

In 1953, James Watson and Francis Crick worked out the double helix, using X-ray pictures of DNA made by Maurice Wilkins and Rosalind Franklin, and Chargaff's rule that in any DNA, the amount of A equals T and G equals C. Its features:

  • Two strands, twisted round each other like a twisted ladder. The backbones are the sides; the base pairs are the rungs.
  • The strands are anti-parallel: one runs 5'→3', the other 3'→5'.
  • Bases pair in only one way: A with T, held by two hydrogen bonds, and G with C, held by three. A purine always faces a pyrimidine, so the ladder is the same width all along.
  • It is a right-handed helix. One full turn (the pitch) is 3.4 nm and has about 10 base pairs, so the pairs are 0.34 nm apart.

Crick also proposed the central dogma: information flows from DNA → RNA → protein. (Some viruses reverse the first step, copying RNA into DNA.)

Packing DNA. The DNA of one human cell, stretched out, would be about 2.2 metres long, yet it fits in a nucleus about a thousandth of a millimetre across. In eukaryotes it is wound round proteins called histones, which are rich in the positively charged amino acids lysine and arginine; the negatively charged DNA wraps round them. Eight histone molecules (an octamer) with about 200 base pairs of DNA wound round them make a nucleosome. Under the electron microscope, chromatin looks like beads on a string. The chain is coiled further into chromatin fibres and, during cell division, into chromosomes.

Chromatin comes in two forms: loosely packed euchromatin, which stains lightly and is active (its genes are read), and tightly packed heterochromatin, which stains darkly and is inactive.

A pairs with T, G with C; the two strands run opposite ways.
A with T, G with C; the strands run opposite ways.

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