103: Model Organisms Appendix

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Bacterium, Escherichia coli

Budding Yeast, Saccharomyces cerevisiae

Bread Mold, Neurospora crassa

Nematode, Caenorhabditis elegans

Mustard Weed, Arabidopsis thaliana

Fruit Fly, Drosophila melanogaster

House Mouse, Mus musculus

Humans differ from other organisms in their cognitive abilities and sense of wonder about their surroundings, and it is this curiosity that drives us to study life. What are we made of? How do we work? To understand humans and other living creatures, scientists have studied a wide variety of organisms, revealing a great deal, including the striking universal features shared by all living things. All organisms use the same amino acids, the same nucleotides, and essentially the same genetic code.

There is more to molecular biology than satisfying our curiosity about how life works. We also strive to understand the causes of disease and to apply our understanding to medicine, agriculture, and technology. This book points out numerous examples of how we have learned about human diseases—their causes and, in some cases, how to treat, cure, or prevent them. Scientists have discovered antibiotics to treat most bacterial infections, have developed vaccines for many types of viral infections, and now understand a great deal more about cancer and its treatments. The vast majority of these discoveries and developments came from studying model organisms.

A Few Organisms Are Models for Understanding Common Life Processes

When a particular species is chosen for intensive investigation by many laboratories, it is referred to as a model organism. This focus on one species by many labs allows the development of a large body of information that provides deep insights into that organism’s living functions. The organism is considered a model because researchers assume that what they learn about it will hold true for related organisms. The particular organism selected for study depends on the questions being asked. Throughout this book, we encounter the contributions of model organisms to our knowledge of molecular biology, and several of the most frequently used organisms are reviewed here.

We should note, however, that sometimes an organism that is “off the beaten track” is studied by only a few laboratories, purely out of curiosity—and these investigations can also have a profound effect on research. For example, Thermus aquaticus gave us Taq polymerase for the polymerase chain reaction (PCR; see the How We Know section at the end of Chapter 7). The study of Tetrahymena thermophila led to the discovery that RNAs can act as catalysts (i.e., ribozymes; see Chapter 16). And studies of some little-known insect viruses, the baculoviruses, gave rise to a recombinant protein expression system that is now in wide use (see Chapter 7).

Focusing on a handful of different organisms is important at a practical level: there are many more species than there are scientists. Indeed, developing an organism into a scientific tool of research is not easy. It requires many years of study to understand the organism and become familiar with its life cycle, proper nutrition, and optimum growth and storage conditions. Especially time-consuming is the development of genetic tools to manipulate the organism’s genome. There are no “standard procedures” for this; genetic tools are largely specific to the organism and are often found by trial and error. This is why it is important that many laboratories work on the same organism and share their knowledge. A critical mass of interest in a model organism eventually leads to international conferences, online databases, and the formation of stock centers that maintain and distribute strains.

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Of all the organisms in the world, why were certain ones chosen as models? The choices were often made with a healthy dose of serendipity. However, some common features underlie the utility of an organism as a model. Model organisms should have a rapid life cycle. They should produce many progeny, so that researchers can find and study rare genetic events. Size is important, too, because large organisms and their numerous large progeny would quickly exhaust the space of a typical laboratory. Model organisms should be easily propagated using a simple and inexpensive food source, and there should be a convenient method of long-term storage for accumulating strains for further study. Table A-1 summarizes some features of the model organisms described here.

Studies on genetics and metabolic pathways in the early 1900s used complex multicellular organisms such as plants, fruit flies, rats, and mice. Later, researchers recognized that single-celled organisms are also amenable to fundamental studies of genes and cellular metabolism. In the 1940s, microbes such as Escherichia coli, yeast, and Neurospora crassa became the most useful models for understanding the basic chemistry of life. They also provided better starting material for biochemists than did animal tissues, because single-celled organisms are a uniform population of identical cells, whereas tissues are composed of different cell types.

No single model organism can answer all questions about life. Single-celled organisms continue to teach us about central aspects of fundamental life processes, such as chromosomal replication, DNA repair, recombination, gene expression, signal pathways, and control of the cell cycle. But single-celled organisms are insufficient for addressing questions about the development of multicellular organisms and most types of disease. Thus, the nematode worm and fruit fly are of enormous use in revealing how multicellular organisms are organized and the basics of how the animal body plan is determined. These organisms also provide insights about many types of disease. Similarly, the mustard weed was chosen as a model organism for plant development.

By far the most useful model of human disease is the mouse. It is, however, not the simplest of model organisms. For ease of growth and DNA manipulation, the mouse pales in comparison with the other model organisms. Genetic strains of mice are costly and time-consuming to construct. But one of the great advantages of the mouse is that 99% of its genes have homologs in the human, including the genes associated with human disease. So despite the difficulties, the mouse is an attractive model in which to study the diseases that afflict us.

We present here a brief overview of several model organisms in use today, including how they have contributed to, and continue to further, our understanding of life. As we have noted, many other organisms have also contributed greatly to our understanding of living processes, including bacteriophages and other viruses, Tetrahymena thermophila (a protozoan), Schizosaccharomyces pombe (fission yeast), Xenopus laevis (frog), and Brachydanio rerio (zebra fish). Before we launch into details of particular model organisms, we briefly describe a few highlights of how we learn about human disease from studying model organisms, in conjunction with genomics and cell culture.

Three Approaches Are Used to Study Human Disease

What causes heart disease, diabetes, neurodegenerative disorders, or cancer? How can these, and other diseases, be prevented, treated, or cured? The study of model organisms is usually the first step in understanding cellular processes that can be altered in human diseases. Using a homolog, we can study a human disease–causing mutation in a model organism and learn how the mutation disrupts the cellular process at the molecular, cellular, or organismal level. In addition, mouse models are often used to test treatments for diseases, as an early step in drug development. Model organisms are often the first avenue to understanding human disease, but human genomics and cell culture can provide an even deeper understanding.

The availability of the complete human genome sequence has been an enormous aid in our understanding of human disease genes at the molecular level, as well as in bioinformatics studies on human evolution and migrations (see Chapter 8). Our capacity for language and written history has played a large role in elucidating the genetics of human disease. In particular, people actively seek out medical and scientific advice for a disease, and often can recall a family pedigree stretching back generations that might provide information about how the disease is transmitted. We see examples of this throughout the book, including hemophilia in royalty (see Figure 2-27), sickle-cell anemia (see Highlight 2-1), and early-onset Alzheimer disease (see Figure 8-11). Identifying human disease genes is a difficult but important task and is being accomplished at a rapid and accelerating rate. Knowledge of the genetics involved in transmitting a disease may help couples plan their families and cope with the possible maladies that may be passed on to their sons and daughters. For scientists, knowledge of a disease gene can help devise a treatment or cure.

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A third way we study ourselves is by culturing individual human cells in vitro. Cells taken directly from the body and then grown in culture typically die within 40 (or fewer) generations. But cells taken from cancer tissue have altered growth control and can often be grown through countless generations; they are referred to as “immortalized.” Cells can sometimes even be removed from normal tissue and then immortalized in tissue culture by infection with particular viruses. Through these and other means, many different types of human tissue cells are grown and maintained in culture, including hepatocytes (liver), renal cells (kidney), fibroblasts (skin), glial cells (nerve), lymphocytes (blood), and myocytes (muscle). By investigating cancer cells and transformation agents, we have also learned a great deal about the genes involved in cancer (see Highlight 12-1). Studies of human and other primate cells in tissue culture have provided important information about surface receptors, protein trafficking, viral entry, and cellular reproduction. Human tissue cells can even be grown in quantities suitable for biochemical studies (see Chapter 7). Recent advances in stem cell research hold promise for the treatment of many diseases and for developing replacement tissue (see Chapter 22).

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