As they work to explain the principles that govern life, biologists often turn to organisms that are easy to manipulate experimentally. Such model organisms have certain characteristics that make them attractive experimental subjects. For example, model organisms:

Biologists have used model organisms to develop principles of genetics that can then be applied more generally to other organisms. You have seen some of these organisms in previous chapters:

To this list we now add the bread mold Neurospora, an ascomycete fungus (see Chapter 30). This mold is haploid for most of its life cycle, so there are no dominant or recessive alleles: all alleles are expressed phenotypically and not masked by a heterozygous condition. Neurospora is easy to grow in the laboratory. Biologists at Stanford University led by George Beadle and Edward Tatum undertook studies to biochemically define the phenotypes in Neurospora.

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Like Garrod, Beadle and Tatum hypothesized that the expression of a specific gene results in the activity of a specific enzyme. They set out to test this hypothesis directly. They grew Neurospora on a nutritional medium containing sucrose, minerals, and biotin, which is the only vitamin that wild-type Neurospora cannot synthesize itself. Using this minimal medium, the enzymes of wild-type Neurospora could catalyze all the metabolic reactions needed for growth.

The scientists then treated the wild-type Neurospora with X rays, which function as a mutagen. A mutagen is something that damages DNA, causing mutations: heritable alterations in the DNA sequence. After the X-ray treatment, some Neurospora strains could no longer grow on the minimal medium. These mutant strains grew only if they were supplied with specific additional nutrients, such as particular vitamins. Beadle and Tatum hypothesized that these genetic strains had mutations in the genes that code for production of enzymes needed to synthesize the additional nutrients. For each mutant strain, the scientists were able to find a single compound that, when added to the minimal medium, supported the growth of that strain. These results suggested that mutations have simple effects, and that each mutation causes a defect in only one enzyme in a metabolic pathway. These conclusions confirmed Garrod’s one-gene, one-enzyme hypothesis.

Mutations provide a powerful way to determine cause and effect in biology. Nowhere has this been more evident than in the elucidation of biochemical pathways. Such pathways consist of sequential events (chemical reactions) in which each event is dependent on the occurrence of the preceding event. The general reasoning is as follows:

Two colleagues of Beadle and Tatum, Adrian Srb and Norman Horowitz, used this experimental approach to isolate Neurospora mutants that could not survive without the amino acid arginine in their growth medium. By adding particular compounds to the medium, Srb and Horowitz were able to identify a series of steps in the biochemical pathway leading to the synthesis of arginine (Figure 14.1a).

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