Model organisms

Category: Methods and techniques

The characteristics of well-chosenmodel organisms, such as their genetic makeup or their development, make them suited to be the subjects of biological research. They are often developed specifically for laboratory study of pure-breeding strains that can be relied upon to provide a consistent medium for experimentation or examination. Biologists planning an experiment might specify a particular breed of rat, for example, whose traits are well defined and that are familiar to their peers. When a given model organism has become the standard in a particular field, it can become a kind of common currency that facilitates exchange among scientists.

Under these circumstances, a great deal of knowledge about individual model organisms may be accumulated rapidly. The crucial assumption, based on the theory of evolution, that underlies the use of specific organisms as models is that species sharing a common ancestor will have fundamental similarities of physiology and biochemistry. Among ubiquitous model organisms are the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, the roundworm Caenorhabditis elegans, the fruit flyDrosophila melanogaster, and the plant Arabidopsis thaliana.

Common Features

Above all else, model organisms must be practical to observe and to use in experiments. They must be easy to breed or propagate and resilient enough to withstand manipulation. For knowledge gained in the study of model organisms to be applicable on a larger scale, the organisms must be representative of the taxonomic group in question. Clearly, the applicability of studies performed on a particular model organism varies, depending on the nature of the inquiry. For example, the yeast S. cerevisiae is broadly representative of the fungi as a whole, but its study may also provide insights into specific molecular processes common to all eukaryotes, including humans. Model organisms are often chosen because they are among the simplest examples of the group being studied. They may have a particularly small genome, a short life cycle, or even a small size that makes them convenient organisms with which to work. They may also lend themselves very well to the study of specific features. For example, fruit flies are commonly used in the study of genetics because they have a small genome from which it is easy to induce and detect mutations.

Well-chosen model organisms, those that possess some or all of the aforementioned characteristics, have been valuable tools for scientific research. Given these characteristics, it is easy to identify two types of scientific inquiry that are well served by the use of model organisms. There are studies in which a category of organisms is investigated by studying one of its simplest members and those in which a particular feature or biological process is illuminated by examining an organism in which it is especially accessible. Thus, the mouse is frequently used as a model for all mammals, and the green alga Chlamydomonas is used to study photosynthesis.

If a specific organism becomes the consensus model for a given category, the situation lends itself well to a speedy advancement of knowledge. The fact that many clusters of researchers choose to focus on the same model promotes collaboration and the more rapid accumulation of a body of knowledge about the organism, enhancing the likelihood of broader insights or theoretical advances. Having a research subject organism in common facilitates communication among researchers and leads to the formation of standard terminology. The widespread study of a single organism promotes the development and propagation of effective techniques for its use and allows for the introduction of standard experimental practices. Many observers have argued that the very success of science as a collaborative activity relies on scientists having some consensus about the tools and objects of their research and the terminology with which they describe it.

Although there are many advantages of a model organism becoming widespread in a particular field, there are some limitations to what can be achieved by the study of model organisms. There must always be a question of the applicability to other species of knowledge gained from the study of a model organism. A poor choice of an organism for a model can hinder the production of scientific knowledge just as much as research on a valid model can be beneficial. There is also the risk that focusing a discipline on one or a few models may inhibit our understanding of diversity. As the botanist Dina Mandoli said, “flowering plants have an estimated 300,000 species . . . no one plant, not even Arabidopsis thaliana, can encompass this enormous diversity at the whole plant, physiologic, chemical, genetic, or molecular level.” It is important, therefore, that research be carried out on enough model organisms to produce an adequate breadth of knowledge. To that end, there are dozens of model plants in use representing a cross section of the kingdom, of which Arabidopsis has been the most widely and successfully employed.

Arabidopsis

Arabidopsis is a genus of the mustard family that is closely related to food plants such as canola, cabbage, cauliflower, broccoli, radish, and turnip. Furthermore, although Arabidopsis is not used in agriculture, it is assumed that its study can lead to better knowledge of crop plants such as corn and soybeans because of evolutionary similarities among the genomes of all angiosperms. In the 1980s Arabidopsis thaliana (thale cress) became the primary model organism used in botany. Many characteristics lend it to such use, including its small size—the plants are a few inches tall when mature—and its short life cycle of less than six weeks. The short life cycle allows researchers to see the effects of experimentation across successive generations in a relatively short span of time. A. thaliana also has a small genome and the least amount of DNA (deoxyribonucleic acid) per haploid cell of any known flowering plant. As a result, it is comparatively easy to trace effects of experimentation to specific genes. It is valuable in the laboratory because of its prolific seed production and the availability of numerous mutations. It may be efficiently transformed with the bacterium Agrobacterium tumefaciens, which is used as a vector for the introduction of foreign DNA to the plant genome.

A. thaliana was publicly recognized for its potential as a model organism in the 1960s. In 1985 it was first promoted as a model for molecular genetic research, and the first molecular map of one of the five A. thaliana chromosomes was published in 1988. In 1996 the Arabidopsis Genome Initiative was begun. Thanks to a multinational effort, by the year 2000 the A. thaliana gene sequence was fully decoded. The sequencing project was itself acclaimed as a model, because the researchers strove to be systematic and comprehensive in their investigation of the genome.

Prior to the widespread use of A. thaliana, many prominent scientists claimed that progress in botanical research was hindered by the study of too many organisms at once. Since A. thaliana became a principal subject of research, botanical knowledge has advanced markedly. Researchers concentrating on A. thaliana have helped unify the studies of classical and molecular genetics, plant development, plant physiology, and plant pathology. These advances have led to a more fundamental understanding of many processes of plant growth and development at a molecular level.

Some specific areas in which A. thaliana research has produced important advances are light perception, floral induction, flower development, and response to pathogenic and environmental stresses. For example, the functions of individual phytochromes, which are photoreceptors involved in many aspects of plant growth and development, were elucidated in A. thaliana. Likewise, the first hormone receptor isolated in plants, that for ethylene, was discovered as a result of using A. thaliana mutants.

Chlorella and Chlamydomonas

Chlorella pyrenoidosa and Chlamydomonas reinhardtii are unicellular green algae that have been used extensively as model organisms. They have many features in common with other model organisms, including short and simple life cycles and easily isolated mutants. Although there is debate as to whether green algae should be included in the plant kingdom, they have been important tools for botanically related research because they are photosynthetic eukaryotic organisms. They therefore offer less complex subjects through which to study many processes that are central to plant life. There are no other unicellular members of the plant kingdom, so study of many important botanical processes may be more easily undertaken on Chlorella or Chlamydomonas than on any plant.

In the mid-twentieth century Melvin Calvin used Chlorella in his Nobel Prize-winning research, which elucidated the cycle involved in photosynthetic carbon fixation that now bears his name, the Calvin cycle. This is a perfect example of model organisms’ value in research. It is often easier to work out a mechanism in a simple organism and see whether it operates the same way in complex organisms—the understanding of which may be the ultimate purpose of the research—than to attempt the investigation on a complex organism in the first place. Once the Calvin cycle had been explained in Chlorella, it was shown to be ubiquitous in the chloroplasts of higher plants.

C. reinhardtii is the green alga most commonly used as a model organism in contemporary research; its genome has also been sequenced. Among the topics of research in which C. reinhardtii is the model organism of choice, one of the most compelling is that of chloroplast biogenesis and inheritance. C. reinhardtii is often referred to as the “green yeast,” and like the yeast S. cerevisiae, it is an important eukaryotic model system. For studying certain aspects of cell biology to which yeast is not applicable, C. reinhardtii is chosen in preference. Such areas include cell motility caused by flagella, phototaxis (phototaxy), photosynthesis, and the study of centrioles, basal bodies, and chloroplasts.

Animal Model Organisms

Caenorhabditis elegans is a type of nematode, or roundworm, that is transparent and only about one millimeter in length. This model animal has been used by scientists to test the concepts of gene therapy and to develop methods for sequencing large amounts of DNA. C. elegans has also provided information about the biology of human diseases such as Alzheimer's disease and cancer. Additionally, research on this worm has enabled scientists to develop effective control measures for plant and animal parasitic roundworms.

Another model animal is the fruit fly, Drosophila melanogaster. Studies of D. melanogaster have allowed scientists to determine that genes reside on chromosomes and have given insight into the nature of mutations. Studies of the development of complex structures such as the eye have provided insight into some of the ways cell specialization is regulated and directed by DNA.

The transparent embryos of the zebra fish, Danio rerio, haved provided an excellent system with which to study the genes that regulate vetebrate development. Additionally, zebra fish have been used in studies investigating the bioaccumulation of organic compounds in the environment.

The common house mouse, Mus musculus, is well known for its use as a model for all mammal life. Mice are useful for genetic study because of the availability of hundreds of single gene mutations. Studies of mice demonstrated that Gregor Mendel's laws of inheritance are as applicable to mammals as to plants. Transgenic genetic analysis of mice has allowed for the creation of mouse strains that mimic human genetic diseases.

Other Prominent Model Organisms

For areas other than those just mentioned, yeast is the most commonly used simple eukaryotic model organism. In 1996 S. cerevisiae became the first eukaryote to have its genome fully sequenced; its size is approximately one-tenth of that of A. thaliana. Around the same time, the genome project was completed for the preeminent prokaryotic model organism, E. coli. This bacterium has become crucial not only as a focus of experiment but also as a biotechnological workhorse. Genes can be cloned by their insertion into E. coli, and gene products can therefore be mass-produced in large-scale fermentations of the bacteria.

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