As soon as genetics emerged as a science at the beginning of the twentieth century, scientists became intrigued by the chemical structure of genes. The information in genes is copied and transmitted from cell to daughter cell millions of times during the life of a multicellular organism, and it survives the process essentially unchanged. What form of molecule could be capable of such accurate and almost unlimited replication and also be able to exert precise control, directing multicellular development as well as the daily life of every cell? What kind of instructions does the genetic information contain? And how can the enormous amount of information required for the development and maintenance of an organism fit within the tiny space of a cell?
The answers to several of these questions began to emerge in the 1940s. At this time researchers discovered, from studies in simple fungi, that genetic information consists largely of instructions for making proteins. Proteins are phenomenally versatile macromolecules that perform most cell functions. As we saw in Chapter 3, they serve as building blocks for cell structures and form the enzymes that catalyze most of the cell’s chemical reactions. They also regulate gene expression (Chapter 7), and they enable cells to communicate with each other (Chapter 15) and to move (Chapter 16). The properties and functions of cells and organisms are determined to a great extent by the proteins that they are able to make.
Painstaking observations of cells and embryos in the late nineteenth century had led to the recognition that the hereditary information is carried on chromosomes—threadlike structures in the nucleus of a eukaryotic cell that become visible by light microscopy as the cell begins to divide (Figure 4–1). Later, when biochemical analysis became possible, chromosomes were found to consist of deoxyribonucleic acid (DNA) and protein, with both being present in roughly the same amounts. For many decades, the DNA was thought to be merely a structural
Figure 4–1 Chromosomes in cells. (A) Two adjacent plant cells photographed through a light microscope. The DNA has been stained with a fluorescent dye (DAPI) that binds to it. The DNA is present in chromosomes, which become visible as distinct structures in the light microscope only when they become compact, sausage-shaped structures in preparation for cell division, as shown on the left. The cell on the right, which is not dividing, contains identical chromosomes, but they cannot be clearly distinguished at this phase in the cell’s life cycle, because they are in a more extended conformation. (b) Schematic diagram of the outlines of the two cells along with their chromosomes. (A, courtesy of Peter Shaw.) element. However, the other crucial advance made in the 1940s was the identification of DNA as the likely carrier of genetic information. This breakthrough in our understanding of cells came from studies of inheritance in bacteria (Figure 4–2). But still, as the 1950s began, both how proteins could be specified by instructions in the DNA and how this information might be copied for transmission from cell to cell seemed completely mysterious. The puzzle was suddenly solved in 1953, when James Watson and Francis Crick derived the mechanism from their model of DNA structure. As outlined in Chapter 1, the determination of the double-helical structure of DNA immediately solved the problem of how the information in this molecule might be copied, or replicated. It also provided the first clues as to how a molecule of DNA might use the sequence of its subunits to encode the instructions for making proteins. Today, the fact that DNA is the genetic material is so fundamental to biological thought that it is difficult to appreciate the enormous intellectual gap that was filled by this breakthrough discovery.
We begin this chapter by describing the structure of DNA. We see how, despite its chemical simplicity, the structure and chemical properties of DNA make it ideally suited as the raw material of genes. We then consider how the many proteins in chromosomes arrange and package this DNA. The packing has to be done in an orderly fashion so that the chromosomes can be replicated and apportioned correctly between the two daughter cells at each cell division. And it must also allow access to chromosomal DNA, both for the enzymes that repair DNA damage and for the specialized proteins that direct the expression of its many genes.