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GENES & CELLS

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THE TEAM  -  Bordeaux le 1er aout 2000

DNA IS THE PRIMARY GENETIC MATERIAL

The realization that genes determines the structure of proteins was a very important milestone in the development of genetics, but it did not have any immediate consequences. So long as the molecular structure of the gene was unknown, there was no way to think constructively about gene-protein relations.

In fact, as recently as 1950 there was no general agreement on which class of molecules genes belonged to. Nevertheless, the best guess was that the gene consisted of deoxyribonucleic acid, a still poorly understood polymeric macromolecule that was just starting to be called by its abbreviation, DNA.

DNA IS SITED ON CHROMOSOMES

For many years it was hoped that as microscopes improved, it might eventually be possible to see genes sitting side by side along chromosomes. But even with the advent in the early 1940s of the first electron microscopes, which had a potential resolution over 100 times greater than of light microscopes, there were disappointments.

The first electron microscope pictures of chromosomes showed no repeating pattern at the molecular level ; this suggested a highly irregular gene structure that would not be simple to interpret. Attemps to purify chromosomes away from other cellular constituents were much more informative, although it was impossible to obtain really pure chromosomes.

Two main chromosomal components were almost invariably found : deoxyribonucleic acid (DNA) and a class of small, positively charged proteins known as the histones ; these, being basic, neutralized the acidity of DNA. DNA had been known to be a major constituent of the nucleous (hence the name nucleous acid) ever since its discovery in 1869 by the Swiss scientist Frederick Miescher.

In the 1920s, with the DNA-specific purple dye developed by the German chemist Robert Feulgen, DNA was found was found to be sited on chromosomes. DNA therefore had the location expected for a genetic material. In contrast, the histones could apparently be ruled out as genetic components because they were absent from many sperm, which contained instead even smaller basic proteins, the protamines. But most biochemists were not inclined to focus attention on DNA. They thought it would not be nearly as specific as the proteins, of which they knew an unlimited number could be constructed by chaining together the 20 amino-acids in different orders.

So it was widely believed that some minor and not yet well characterized protein component of the chromosomes might be found to be the true genetic material.

CELLS CONTAIN RNA AS WELL AS DNA

Already late in the nineteenth century it had been discovered that cells have a second kind of nucleic acid -what we know called ribonucleic acid (RNA)-. Unlike DNA, which is located primarily in the nucleous, RNA is found in abundance in the cytoplasm as well as in the nucleous. Within the nucleous, RNA is concentrated in a few dense granules (nucleoli) that are attached to chromosomes.

Both DNA and RNA resemble proteins in that they are constructed from many smaller building blocks linked end to end. However, nucleotides, the building blocks of nucleid acid are more complex than any amino acid. Each nucleotide contains a phosphate group, a sugar moiety, and either a purine or pyrimidine base (flat ring shaped molecules containing carbon and nitrogen). When nucleotides are linked together in large numbers, they are called polynucleotides.

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