Chapter 8 Section 1: Gene Expression Overview PDF

AN OVERVIEW OF GENE EXPRESSION Gene expression is the complex process by which cells selectively direct the synthesis of the many thousands of proteins and RNAs encoded in their genome. But how do cells coordinate and control such an intricate process—and how does an individual cell “know” which of...

AN OVERVIEW OF GENE EXPRESSION Gene expression is the complex process by which cells selectively direct the synthesis of the many thousands of proteins and RNAs encoded in their genome. But how do cells coordinate and control such an intricate process—and how does an individual cell “know” which of its genes to express? This decision is an especially important problem for animals because, as they develop, their cells become highly specialized, ultimately generating an array of muscle, nerve, and blood cells, along with the hundreds of other cell types seen in the adult. Such cell differentiation arises because cells produce and accumulate different sets of RNA and protein molecules: that is, they express different genes. The Different Cell Types of a Multicellular Organism Contain the Same DNA The evidence that cells have the ability to change which genes they express without altering the nucleotide sequence of their DNA comes from experiments in which the genome from a differentiated cell is made to direct the development of a complete organism. If the chromosomes of the differentiated cell were altered irreversibly during development—for example, by jettisoning some of their genes—they would not be able to accomplish this feat. Consider, for example, an experiment in which the nucleus is taken from a skin cell in an adult frog and injected into a frog egg from which the nucleus has been removed. In at least some cases, that doctored egg will develop into a normal tadpole (Figure 8–2). https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 1 of 6 Thus, the nucleus from the transplanted skin cell cannot have lost any of the DNA sequences needed to generate all of the other types of cells. Nuclear transplantation experiments carried out with differentiated cells taken from adult mammals—including sheep, cows, pigs, goats, and mice—have produced similar results. And in plants, individual cells removed from a carrot, for example, can regenerate an entire adult carrot plant. Figure 8–2 Differentiated cells contain all the genetic instructions needed to direct the formation of a complete organism. (A) The nucleus of a skin cell from an adult frog transplanted into an “enucleated” egg—one whose nucleus has been destroyed—can give rise to an entire tadpole. The broken arrow indicates that to give the transplanted genome time to adjust to an embryonic environment, a further transfer step is required in which one of the nuclei is taken from the early https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 2 of 6 embryo that begins to develop and is put back into a second enucleated egg. (B) In many types of plants, differentiated cells retain the ability to “de-differentiate,” so that a single cell can proliferate to form a clone of progeny cells that later give rise to an entire plant. (C) A nucleus removed from a differentiated cell of an adult cow can be introduced into an enucleated egg from a different cow to give rise to a calf. Different calves produced from the same differentiated cell donor are all clones of the donor and are therefore genetically identical. The cloned sheep Dolly was produced by this type of nuclear transplantation. (A, modified from J.B. Gurdon, Sci. Am. 219:24–35, 1968.) These experiments all demonstrate that the DNA in specialized cell types of multicellular organisms still contains the entire set of instructions needed to form a whole organism. They also prove, definitively, that the various cell types of an organism differ not because they contain different genes, but because they express them differently. Different Cell Types Produce Different Sets of Proteins The extent of the differences in gene expression between different cell types may be roughly gauged by comparing the protein composition of cells in liver, heart, brain, and so on. In the past, such analysis was performed by two-dimensional gel electrophoresis (see Panel 4–5, p. 173). Nowadays, the total protein content of a cell can be rapidly analyzed by a method called mass spectrometry (see Figure 4–55). This technique is much more sensitive than electrophoresis and it enables the detection of proteins that are produced even in minor quantities. Both techniques reveal that many proteins are common to all the cells of a multicellular organism. These housekeeping proteins include, for example, RNA polymerases, DNA repair enzymes, ribosomal proteins, enzymes involved in glycolysis and other basic metabolic processes, and many of the proteins that form the https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 3 of 6 cytoskeleton. Each different cell type, in addition, produces specialized proteins that are responsible for that cell’s distinctive properties. In mammals, for example, hemoglobin is made almost exclusively in developing red blood cells. Gene expression can also be studied by cataloging a cell’s RNA molecules, including the mRNAs that encode protein. The most comprehensive methods for such analyses involve determining the nucleotide sequence of all RNAs made by the cell, an approach that can also reveal the relative abundance of each. Estimates of the number of different mRNA sequences in human cells suggest that, at any one time, a typical differentiated human cell expresses perhaps 5000–15,000 of its approximately 20,000 protein-coding genes—although some of these are expressed at very low levels. And studies of a variety of tissue types confirm that the collection of expressed mRNAs differs significantly from one cell type to the next. A Cell Can Change the Expression of Its Genes in Response to External Signals Although each cell type in a multicellular organism expresses its own set of genes, these collections are not static. Specialized cells are capable of altering their patterns of gene expression in response to extracellular cues. For example, if a liver cell is exposed to the steroid hormone cortisol, the production of several proteins is dramatically increased. Released by the adrenal gland during periods of starvation, intense exercise, or prolonged stress, cortisol signals liver cells to boost the production of glucose from amino acids and other small molecules. The set of proteins whose production is induced by cortisol includes enzymes such as https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 4 of 6 tyrosine aminotransferase, which helps convert tyrosine to glucose. When the hormone is no longer present, the production of these proteins returns to its resting level. Other cell types respond to cortisol differently. In fat cells, for example, the production of tyrosine aminotransferase is reduced instead of elevated; some other cell types do not respond to cortisol at all. The fact that different cell types often respond in different ways to the same extracellular signal contributes to the specialization that gives each cell type its distinctive character. Gene Expression Can Be Regulated at Various Steps from DNA to RNA to Protein If differences among the various cell types of an organism depend on the particular genes that each cell expresses, at what level is this control of gene expression exercised? As we discussed in the previous chapter, there are many steps in the pathway leading from DNA to protein, and each of them can in principle be regulated. A eukaryotic cell can control (1) when and how often a given gene is transcribed, (2) how an RNA transcript is spliced or otherwise processed, (3) which mRNAs are exported from the nucleus to the cytosol, (4) how quickly certain mRNA molecules are degraded, (5) which mRNAs are translated into protein by ribosomes, (6) how rapidly a protein is destroyed, or (7) whether a protein is activated once it has been made. In eukaryotic cells, gene expression can be regulated at each of these steps (Figure 8–3). Most are similarly regulated in bacteria. For most genes, however, the control of transcription (shown in step 1) is paramount. This makes sense because only https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 5 of 6 transcriptional control can ensure that no unnecessary intermediates are synthesized. Thus it is the regulation of transcription—and the DNA and protein components that determine which genes a cell transcribes into RNA—that we address first. Figure 8–3 Eukaryotic cells can control which proteins they contain by regulating various steps along the pathway togene expression. Although examples of regulation at each of these steps are known, for most genes the main site of control is step 1: transcription of a DNA sequence into RNA. Note that many (but not all) proteins require additional, post-translational modifications to become fully activated. https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/126!/4?control=control-toc&lti=true 10/12/23, 8:43 PM Page 6 of 6