An organism’s DNA encodes all of the RNA and protein molecules required to construct its cells. Yet a complete description of the DNA sequence of an organism—be it the few million nucleotides of a bacterium or the few billion nucleotides of a human—no more enables us to reconstruct the organism than a list of English words enables us to reconstruct a play by Shakespeare. In both cases, the problem is to know how the elements in the DNA sequence or the words on the list are used. Under what conditions is each gene product made, and, once made, what does it do?
In this chapter, we focus on the first half of this problem—the rules and mechanisms that enable a subset of genes to be selectively expressed in each cell. These mechanisms operate at many levels, and we shall discuss each level in turn. But first we present some of the basic principles involved.
The different cell types in a multicellular organism differ dramatically in both structure and function. If we compare a mammalian neuron with a liver cell, for example, the differences are so extreme that it is difficult to imagine that the two cells contain the same genome (Figure 7–1). For this reason, and because cell differentiation often seemed irreversible, biologists originally suspected that genes might be selectively lost when a cell differentiates. We now know, however, that cell differentiation generally occurs without changes in the nucleotide sequence of a cell’s genome.
the Different Cell types of a Multicellular Organism Contain the Same DnA
The cell types in a multicellular organism become different from one another because they synthesize and accumulate different sets of RNA and protein molecules. The initial evidence that they do this without altering the sequence of their DNA came from a classic set of experiments in frogs. When the nucleus of a fully differentiated frog cell is injected into a frog egg whose nucleus has been removed, the injected donor nucleus is capable of directing the recipient egg to
Figure 7–1 A neuron and a liver cell share the same genome. the long branches of this neuron from the retina enable it to receive electrical signals from many other neurons and convey them to neighboring neurons. the liver cell, which is drawn to the same scale, is involved in many metabolic processes, including digestion and the detoxification of alcohol and other drugs. Both of these mammalian cells contain the same genome, but they express different sets of rnAs and proteins. (neuron adapted from S. ramón y Cajal, histologie du Systeme nerveux de l’homme et de vertebres, 1909–1911. paris: Maloine; reprinted, Madrid: C.S.i.C, 1972.) 370 Chapter 7:  Control of Gene expression produce a normal tadpole (Figure 7–2A). The tadpole contains a full range of differentiated cells that derived their DNA sequences from the nucleus of the original donor cell. Thus, the differentiated donor cell cannot have lost any important DNA sequences. A similar conclusion came from experiments performed with plants. When differentiated pieces of plant tissue are placed in culture and then dissociated into single cells, often one of these individual cells can regenerate an entire adult plant (Figure 7–2B). And the same principle has been more recently demonstrated in mammals that include sheep, cattle, pigs, goats, dogs, and mice (Figure 7–2C).
Most recently, detailed DNA sequencing has confirmed the conclusion that the changes in gene expression that underlie the development of multicellular organisms do not generally involve changes in the DNA sequence of the genome.
Different Cell types Synthesize Different Sets of rnAs and proteins
As a first step in understanding cell differentiation, we would like to know how many differences there are between any one cell type and another. Although we