Chapter 19
Eukaryotic genomes
Click here to view slides for this lecture.
I. Introduction
Regulation of gene expression in eukaryotic systems employs all of the strategies that we have seen in bacteria. Transcriptional initiation in the primary point of regulation, and decisions are mediated by proteins that assemble near the promoters of regulated genes. In our discussion of transcription and translation, we noticed that eukaryotic gene expression involves a number of steps that are not present in prokaryotes: mRNA splicing, capping, polyadenylation, and transport. In general, eukaryotes use positive regulation of transcription mediated by proteins assembling at or near the promoter. Negative regulation in eukaryotes usually involves packaging DNA into chromatin (Figure 19.1) where in is not available for expression. Today, we will discuss a number of other ways that prokaryotes and eukaryotes differ in the process of gene expression.
II. Eukaryotic Genomes
The survival strategy for most bacteria is centered on metabolic adaptability and a short doubling time. Many bacteria can double in less than twenty minutes under ideal conditions. Bacterial genomes, then, must contain enough information to specify a broad array of biosynthetic and catabolic systems, but must also be small enough for rapid duplication. Multicellular eukaryotes are not as dependant on rapid doubling as are bacteria. For most, the generation time is much longer than the time required to replicate the genome, so that this step is not rate-limiting as it is in bacteria. Consequently, there is less selective pressure for the control of genome size in most eukaryotes. We have already seen that introns represent a part of the genome that does not specify protein sequence. Other non-coding genomic elements include satellite DNA, telomeres, transposons, and pseudogenes.
Eukaryotic genomes also contain examples of multigene families that have arisen by duplication and divergent evolution. The classic example of alpha- and beta-hemoglobin families is shown in Figure 19.3 of your text. Ribosomal DNA, in contrast, is often repeated thousands of times per genome, in order to have sufficient numbers of ribosomes. Note that special care must be taken to prevent divergent drift between multiple copies of rDNA.
III. Control of Eukaryotic Gene Expression
Like prokaryotes, eukaryotes regulate gene expression based on environmental conditions. Added to this type of adaptive regulation is regulation based on cell type, with liver and brain cells, for example, expressing very different constellations of genes. Regulation may also be based on the developmental stage of the cell in question. Some genes that are critical to development are never again expressed in the adult organism.
Superimposed on the greater complexity of eukaryotic gene expression are a number of steps not present in prokaryotes. Before genes can be expressed they must be unpackaged from the condensed chromatin state to the double helix accessible to proteins that regulate which genes are to be expressed. Figure 19.1 shows the levels of DNA packaging from double helix to chromosome.
Figure 19.7 reviews some of the other steps that offer opportunities for gene regulation in eukaryotic cells.
IV. Mutation and Cancer
The creation of a cancerous cell is a multistep process. Usually several checks on uncontrolled cell division have to be overcome before a cell can enter a cancerous state. Figure 19.13 shows how mutations in genes that regulate the cell cycle can lead to loss of control of cell division. Protooncogene mutations that result in overproduction or in hyperactive proteins promote cell cycle progression. Any mutation that leads to loss of function of tumor suppressors also promotes cell cycle progression by removing inhibiotion of the cell cycle. The steps in the formation of some colorectal cancers (Figure 19.14) have been elucidated - the loss of several tumor-suppressor genes, as well as the activation of the ras oncogene. In any given cell the chance of each of these events occurring is very small, and so the probability of any cell becoming cancerous is near zero. If, though, an individual inherits defects in one or more of these proteins, the chances of cancer rise dramatically. Progression is accelerated in some cases by the mutagenic effects of an early step. Note that oncogenes tend to be dominant alleles, while loss-of-tumor-suppressor mutations tend to be recessive alleles.
The following figures were scanned from the Sept, 1996 issue of Scientific American. This special issue on cancer has several interesting articles on topics ranging from molecular biology to epidemiology.
