With the basic laws of inheritance largely worked out by the end of the 1960s, a new era of applying genetic analysis to a broad spectrum of biological questions flourished. To this end, much effort has been and continues to be invested in developing the resources and tools to address these questions. Geneticists focused their research on a small number of species known as “model organisms” that are well suited for genetic analysis. They also developed an impressive array of tools for manipulating and analyzing DNA.

Geneticists make special use of a small set of model organisms for genetic analysis. A model organism is a species used in experimental biology with the presumption that what is learned from the analysis of that species will hold true for other species, especially other closely related species. The philosophy underlying the use of model organisms in biology was wryly expressed by Jacques Monod: “Anything found to be true of E. coli must also be true of elephants.”¹

As genetics matured and focused on model organisms, Mendel’s pea plants fell to the wayside, but Morgan’s fruit flies rose to prominence to become one of the most important model organisms for genetic research. New species were added to the list. An inconspicuous little plant that grows as a weed called Arabidopsis thaliana became the model plant species and a minute roundworm called Caenorhabditis elegans that lives in compost heaps became a star of genetic analysis in developmental biology (Figure 1-11).

What features make a species suitable as a model organism? (1) Small organisms that are easy and inexpensive to maintain are very convenient for research. So fruit flies are good, blue whales not so good. (2) A short generation time is imperative because geneticists, like Mendel, need to cross different strains and then study their first- and second-generation hybrids. The shorter the generation time, the sooner the experiments can be completed. (3) A small genome is useful. As you will learn in Chapter 15, some species have large genomes and others small genomes in terms of the total number of DNA base pairs. Much of the extra size of large genome species is composed of repetitive DNA elements between the genes. If a geneticist is looking for genes, these can be more easily found in organisms with smaller genomes and fewer repetitive elements. (4) Organisms that are easy to cross or mate and that produce large numbers of offspring are best.

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As you read this textbook, you will encounter certain organisms over and over. Organisms such as Escherichia coli (a bacterium), Saccharomyces cerevisiae (baker’s yeast), Caenorhabditis elegans (nematode or roundworm), Drosophila melanogaster (fruit fly), and Mus musculus (mice) have been used repeatedly in experiments and revealed much of what we know about how inheritance works. Model organisms can be found on branches of the tree of life (see Figure 1-11), representing bacteria, fungi, algae, plants, and invertebrate and vertebrate animals. This diversity enables each geneticist to use a model best suited to a particular question. Each model organism has a community of scientists working on it who share information and resources, thereby facilitating each other’s research.

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Mendel’s experiments were possible because he had several different varieties of pea plants, each of which carried a different genetic variant for traits such as purple versus white flowers, green versus yellow seeds, or tall versus dwarf stems. For each of the model species, geneticists have assembled large numbers of varieties (also called strains or stocks) with special genetic characters that make them useful in research. There are strains of fruit flies that have trait variants such as red versus white eyes. There are strains of mice that are prone to develop specific forms of cancer or other disease conditions such as diabetes. For baker’s yeast, there is a collection of nearly 5000 deletion stocks, each of these having just one gene deleted from the genome. These stocks enable geneticists to study the function of each gene by examining how yeast is affected when the gene is removed. Since baker’s yeast has about 6000 total genes, this collect of 5000 deletion stocks covers most of the genes in the genome.

The different strains of each model organism are available to researchers through stock centers that maintain and distribute the strains. Lists of available stocks are on the Internet (see Appendix B). To view an example for mouse stocks, go to the link http://jaxmice.jax.org/. Then, click the “Find JAX mice” button at the top of the page. Next, enter the word “black” in the search field and click the Search button. Now, click the “C57BL/6J” link. You will see an image and information on a commonly used C57-Black mouse strain. Other search terms such as “albino” or “obese” will link you with strains with other features.

Geneticists and biochemists have also created an incredible array of tools for characterizing and manipulating DNA, RNA, and proteins. Many of these tools are described in Chapter 10 or in other chapters relevant to a specific tool. There are a few themes to mention here.

First, geneticists have harnessed the cell’s own machinery for copying, pasting, cutting, and transcribing DNA, enabling researchers to perform these reactions inside test tubes. The enzymes that perform each of these functions in living cells have been purified and are available to researchers: DNA polymerases can make a copy of a single DNA strand by synthesizing a matching strand with the complementary sequence of A’s, C’s, G’s, and T’s. Nucleases can cut DNA molecules in specific locations or degrade an entire DNA molecule into single nucleotides. Ligases can join two DNA molecules together end-to-end. Using DNA polymerase or other enzymes, DNA can also be “labeled” or “tagged” with a fluorescent dye or radioactive element so that the DNA can be detected using a fluorescence or radiation detector.

Second, geneticists have developed methods to clone DNA and the genes it encodes. Here, cloning refers to making many copies (clones) of a DNA molecule. The common way of doing this involves isolating a relatively small DNA molecule (up to a few thousand base pairs in length) from an organism of interest. The DNA molecule might be an entire gene or a portion of a gene. The molecule is inserted into a host organism (often E. coli) where it is replicated many times by the host’s DNA polymerase. Having many copies of a gene is important for a vast array of experiments used to characterize and manipulate it.

Third, geneticists have developed methods to insert foreign DNA molecules into the genomes of many species, including those of all the model organisms. This process is called transformation, and it is possible, for instance, to transform genes from one species into the genome of another. The recipient species then becomes a genetically modified organism (GMO). Figure 1-12 shows a tobacco plant in which a gene from the firefly was inserted, enabling the tobacco plant to emit light or glow in the dark.

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Fourth, geneticists have developed a large set of methods based on hybridizing DNA molecules to one another (or to RNA molecules). The two complementary strands of DNA in the double helix are bound together by hydrogen bonds, either G ≡ C or A = T. These bonds can be broken by heat (denatured) in an aqueous solution to give two single-stranded DNA molecules (Figure 1-13a). When the solution is cooled under controlled conditions, DNA molecules with complementary strands will preferentially hybridize with one another. DNA hybridization methods have enabled many discoveries. For example, the cloned DNA of a gene can be tagged with a fluorescent dye and then hybridized to chromosomes fixed on a microscope slide, revealing the chromosome on which the gene is located (Figure 1-13b).

Fifth, geneticists and biochemists have developed multiple methods for determining the exact sequence of all the A’s, C’s, G’s, and T’s in the genomes, chromosomes, or genes of an organism. The process used to decipher the exact sequence of A’s, C’s, G’s, and T’s in a DNA molecule is called DNA sequencing, and it has allowed geneticists to read the language of life.

Finally, over the last 20 years, researchers have created molecular and mathematical tools for analyzing the entire genome of an organism in a single experiment. These efforts gave birth to the field of genomics—the study of the structure and function of entire genomes (see Chapter 14). Genomic tools have enabled geneticists to assemble mind-boggling amounts of information on model organisms, including the complete DNA sequence of their genome, lists of all their genes, catalogs of variants in these genes, data on the cell and tissue types in which each gene is expressed, and much more. To get an idea of what is available, try browsing Fly Base (http://flybase.org/), the genomic data site for the fruit fly (see also Appendix B).

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