Despite rapid advances in classical genetics in the early years of the twentieth century, the nature of genes and their mode of function remained obscure. Indeed many geneticists preferred to think of them as abstract entities. Genes gained some substance through the examination of polytene chromosomes. These are parallel aggregates of a number of identical chromosomes, found in the salivary glands of some insects, including Drosophila (Figure 1 and Figure 2). Following proper staining and viewing under the light microscope, they show a banded pattern, and some bands can be correlated with genes mapped by the Sturtevant–Morgan technique. Such studies reinforced the image of genes as physical objects, but of what were they made?
Fig1. Polytene chromosomes with typical banding patterns. The banding pat terns of Drosophila polytene chromosomes were depicted by Calvin Bridges as early as 1935 and are still widely used to identify chromosomal rearrangements and deletions. A fluorescent image of the Drosophila salivary gland chromosomes stained for two different proteins, BRAMA in green and Pol II in red, is presented. The two proteins show a high degree of overlap. [From Armstrong JA, Papoulas O, Daubresse G et al. (2002) EMBO J 21: 5245–5254. With permission from John Wiley & Sons, Inc.]
Fig2. Banding patterns of polytene chromosomes reflect the transcriptional activity of chromosome regions. A fluorescent image of heat-shock-induced chromo some puffs, loci 87A/C, in Drosophila melanogaster chromosomes is shown. Inactive genes that are located in compact chromatin form condensed bands. In puffing, the material of the bands loosens and becomes decompacted, and local swelling of the chromosome region occurs. DNA is stained with 4′,6-diamidino-2-phenylindole (DAPI), shown in blue, while the heat-shock factor (HSF) gene, encoding a transcriptional activator of genes induced by heat shock, is shown in red. The merged image on the right indicates that the transcriptional activator gene is located in the puffed, decondensed regions. [From Armstrong JA, Papoulas O, Daubresse G et al. (2002) EMBO J 21: 5245–5254. With permission from John Wiley & Sons, Inc.]
This same period saw the beginnings of protein studies, and the function of proteins as enzymes was well established. Probably for this reason, and because of misunder standings of the nature of nucleic acids, most researchers before about 1940 assumed that genes were proteinaceous in composition. It was also becoming evident, however, that genes must dictate protein structure. Certain disease states that depended on the loss of one enzyme function exhibited Mendelian inheritance; this early observation led to the dictum “one gene, one enzyme.” After the brilliant work in several laboratories on sickle cell anemia (Box 1), this dictum had to be modified to one gene, one polypeptide chain. Today we realize that not only protein sequences but also non-protein-coding RNA sequences are dictated by genes, leading to further attempts to properly define a gene. As we see in Chapter 7, the definition of the term gene is still evolving, with a new definition recently proposed in 2012 as a result of studies on the human genome.
