1 The biological role of nucleic acids
1.1 Early observations
Some of the earliest observations of macromolecules within living cells were of nucleic acids in the form of chromosomes. These long dark-staining objects, which became visible in the nucleus of cells at specific stages of cell division, were large enough to be detected using primitive light microscopes. Giant polytene chromosomes, found in certain cells such as the salivary gland cells of Drosophila (see Figure 1a), contain many thousands of copies of each chromosomal DNA aligned in register alongside each other and hence were readily observed by early microscopists. From such early observations came the term ‘nucleic acid’, referring to the nuclear location of these structures. When the thread-like nucleic acids were isolated from cells and analysed biochemically, they were found to be composed of three relatively simple components: sugar, phosphate and base. For many years, this chemical composition, which is relatively simple compared to that of proteins, led to nucleic acids being overlooked as candidate genetic macromolecules. Of course, we now know much more about the structure, function and variety of nucleic acids, even down to the order of every base along the DNA and RNA chains of complex genomes such as are found in mammals and plants; and the central importance of nucleic acids in all living organisms cannot be overestimated.
In autumn 2003, completed genome sequences were available for 18 Archaebacteria, 140 Eubacteria, 1364 viruses and 20 eukaryotes, including four plants.
Figure 1:Early observations were made using light microscopes, e.g. of polytene chromosomes in Drosophila salivary gland cells (a), and of chromosomes in plant cells (b). More recent developments allow us to visualize DNA directly, using the atomic force microscope (AFM) (c), or the electron microscope (EM) (d). The AFM produces a molecular view of a surface indirectly, by measuring deflections caused by atomic-level weak attractive forces between a carbon-tipped probe as it passes across the sample surface. Whilst AFM does not require any chemical modification of the DNA, in EM the macromolecular structure of nucleic acids is labelled with heavy metals to reveal a high level of structural detail. Major cellular RNA-containing components, such as ribosomes, can also be seen using the EM (e). Under normal microscopy conditions, mRNA can be seen on Drosophila chromosomes at sites of high gene transcription (f).